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Neuropsychological Similarities in Lateralized Parkinsonism
Abstract
Parkinson's disease (PD) patients who have left or right predominance of motor symptoms may exhibit cognitive differences. Previous research found greater neuropsychological impairment in patients with both right and left motor predominance, and some found no differences. Variability in overall severity of disease among the patients studied makes evaluation of these reports difficult. We examined the possibility that neuropsychological differences may occur in different stages of disease by comparing patients with mild unilateral disease (Exp. 1) and advanced disease (Exp. 2). Results indicated that while overall cognitive impairment increased with advancing disease, the pattern of neuropsychological impairments were not different with respect to laterality of motor symptoms in either experiment.
... Dopamine neuromodulation is intrinsic to processes of movement and motor learning, cognition, reward processing, food intake, nociception, and endocrine and autonomic regulation. Studies on the lateralization of cognitive functions in patients with PD yielded conflicting results: some reported that neuropsychological deficits are consistent with the lateralization of motor symptoms [4][5][6][7][8][9][10], whilst others failed to find a correlation [11][12][13][14][15]. A limitation of several of these studies is that they prevalently investigated global lateralized brain functions in patients with variable disease severity. ...
... Our data on cognition confirm a number of earlier studies reporting no association between laterality of motor impairment and executive functions [12,13,15] and challenge other studies suggesting that patients with left hemisphere involvement have a reduced performance in verbal fluency [7,9,10], digit span [7], and Wisconsin Card Sorting Test [8,10]. The strict inclusion criteria of this protocol probably accounts for the observed normal cognitive features. ...
... Some earlier studies included patients with different degrees of disease severity [7][8][9], whereas others also included patients Behavior, personality in lateralized PD with dementia [10]. In keeping with our observation, previous studies that matched patient groups for disease severity and overall intellectual impairment failed to find cognitive differences in lateralization [12,13,15]. The selection of patients with mild PD features allowed to avoid the inclusion of subjects with cortical Lewy body pathology and to emphasize differences related to dopaminergic innervation of the basal ganglia. ...
Dopamine neurotransmission plays a key role in several brain activities, including motor, cognitive, and behavioral functions. Parkinson's disease (PD) typically begins with asymmetrical motor features related to asymmetrical dopamine denervation. This study was designed to examine whether distinct cognitive, behavioral, and personality features are related to this asymmetry.
Fifty-six patients with mild PD and lateralized motor features were grouped according to dominant side of motor features and evaluated using a neuropsychological assessment focused on attention and executive functions, impulse control disorders, and personality inventory.
There were no differences in neuropsychological functions between patients with right and left lateralized PD, but differences occurred in personality features. Patients with motor impairment predominant on the left-hand side had prevalence of hypomania and conversion profile.
This study suggests that side dominance of dopaminergic denervation may be related to personality features in patients with PD that could influence behavioral aspects.
... On the other hand there are also studies that did not find differences between hemiparkinsonian groups in visual mem-ory, visuoconstruction, and other visuospatial areas (Agniel et al., 1991;Finali et al., 1995;Goldenberg, 1989;Hietanen & Teräväinen, 1989;Huber et al., 1989;Natsopoulos et al., 1993;Raskin et al., 1992;Riklan et al., 1990;Spicer et al., 1988). The few studies which also incorporated a control group mostly revealed inferior performance of the Parkinson groups compared to healthy controls. ...
... This confirms the results of several studies (Agniel et al., 1991;Amick et al., 2006;Finali et al., 1995;Hietanen & Teräväinen, 1989;Riklan et al., 1990). Other studies however found differences of right and left Hemiparkinson patients compared to controls (Blonder et al., 1989;Chouza et al., 1984;Huber et al., 1989). ...
Parkinsons disease is characterized by tremor, rigidity, and bradykinesia. The study of patients with predominant symp- toms on one side of the body (hemiparkinsonism) is clinically relevant for different disciplines. The predominantely affect- ed side of the dopamine system in patients with Parkinsons disease might have differential effects on certain functions. The functional architecture of the basal ganglia suggests their involvement in visuocognitive processes. Earlier studies have yielded mixed results. Only few studies examined differences in visuocognitive functions in hemiparkinsonism compared to a control group. The aim of our study was to examine such functions and their interrelations in hemiparkinsonism in comparison to a control group in detail. We compared 22 Par- kinson patients with predominantely right sided symptoms (Parkinson right), 22 Parkinson patients with predominantely left sided symptoms (Parkinson left) and 22 healthy controls on several visuocognitive measures. We found no significant differences between the three groups in visuoconstruction, visual memory, mental rotation, and movement imagery. Significant differences were found in a self-rating instrument of visual imagery. The control group generally has a clearer visual imagination than the Parkinson left group. On sub- scale level the control group has a clearer geometric-sche- matic imagery than the Parkinson right and the Parkinson left group. The control group further has a clearer phantasy imagery than the Parkinson left group. In the Parkinson right group there is a significant association of self-rated visual imagery and visual memory. In the Parkinson left group there are significant correlations between geometric-schematic im - agery on one side and visual memory and mental rotation on the other side. In the control group there are significant as - sociations between mental rotation and figural memory and between visuoconstruction and visual reproduction. These correlational patterns suggest that there are different under- lying mechanisms in the three groups that are relevant for performance in visuocognitive tasks. Our results suggest no differential role of the basal ganglia in objective neuropsy- chological measures of visual cognition. The self-rated visu- al imagery ability seems to be mainly mediated by the right basal ganglia because especially the Parkinson left group is impaired in this area. The definition of laterality of motor symptoms should be standardized.
... On the other hand there are also studies that did not find differences between hemiparkinsonian groups in visual mem-ory, visuoconstruction, and other visuospatial areas (Agniel et al., 1991;Finali et al., 1995;Goldenberg, 1989;Hietanen & Teräväinen, 1989;Huber et al., 1989;Natsopoulos et al., 1993;Raskin et al., 1992;Riklan et al., 1990;Spicer et al., 1988). The few studies which also incorporated a control group mostly revealed inferior performance of the Parkinson groups compared to healthy controls. ...
... This confirms the results of several studies (Agniel et al., 1991;Amick et al., 2006;Finali et al., 1995;Hietanen & Teräväinen, 1989;Riklan et al., 1990). Other studies however found differences of right and left Hemiparkinson patients compared to controls (Blonder et al., 1989;Chouza et al., 1984;Huber et al., 1989). ...
... PD has been viewed by many experts as a lateralised disorder with each hemisphere having designated motor and cognitive responsibilities. Thus, the side of symptom onset may carry differential effects on cognitive, visuospatial and perceptuo-motor functions [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although some studies did not demonstrate a hemispheric difference on cognitive functioning [8,11] the majority of studies revealed some association with cognitive functions, especially those known to be located in a specific hemisphere [4,6,9,10,13,14]. ...
... Thus, the side of symptom onset may carry differential effects on cognitive, visuospatial and perceptuo-motor functions [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although some studies did not demonstrate a hemispheric difference on cognitive functioning [8,11] the majority of studies revealed some association with cognitive functions, especially those known to be located in a specific hemisphere [4,6,9,10,13,14]. ...
Researchers have consistently observed in right-handed individuals across normal and disease states that the 'dominant' left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson's disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right 'composite scores', were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
While DBS on the 'dominant' left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
... Regarding the ability to pay attention, as calculated by the number memory test, most studies have found that performance is generally within normal limits [1,2]. Attention deficits are common in patients with Parkinson's disease and are more common in complex trials requiring alternating or maintaining attention [3, 4,5] and in mental calculations require constant mental monitoring [2,6]. ...
Presentation and Interpretation of Neurocognitive Deficits of a Young Female Patient
With Parkinson's Disease
... Regarding the ability to pay attention, as calculated by the number memory test, most studies have found that performance is generally within normal limits [1,2]. Attention deficits are common in patients with Parkinson's disease and are more common in complex trials requiring alternating or maintaining attention [3, 4,5] and in mental calculations require constant mental monitoring [2,6]. ...
In Cognitive Neuropsychology, data from case studies are used to
create models, to draw conclusions about the functional characteristics
of normal intellect, and to explore deficient and intact mental
abilities. The results of case studies have become equally reliable
data through which a theory is supported or not. Parkinson's
disease is one of the most common neurodegenerative diseases
with an average incidence of about 200 / 100,000. The frequency
depends on age, as up to the age of 40 it does not exceed 3-4 /
100,000 while from the age of 70 onwards it exceeds 50 / 100,000.
The present study examines the cognitive deficits of a 42-year-old
woman diagnosed with Parkinson's disease.
... Regarding the ability to pay attention, as calculated by the number memory test, most studies have found that performance is generally within normal limits [1,2]. Attention deficits are common in patients with Parkinson's disease and are more common in complex trials requiring alternating or maintaining attention [3, 4,5] and in mental calculations require constant mental monitoring [2,6]. ...
... 21 Subsequent studies were more equivocal. 18 " 2047 Two of these 20 -47 asserted that neuropsychological performance differed as a function of side of maximal motor involvement. Patients with signs lateralized to the right were reportedly more impaired on dominant hemisphere function (e.g. ...
Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson’s disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.
... The lateralization of motor symptoms is associated with a more severe contralateral degeneration of dopaminergic neurons (Haaxma et al., 2010), which is in turn responsible for a hypodopaminergic state in the striatum and frontal regions (Marie et al., 1995;Mattay et al., 2002;Cheesman et al., 2005). The correlation between dopamine innervation and expression of cognitive capacities (Nieoullon, 2002) indicates that dopaminerelated asymmetry could impact on cognitive resources (Huber et al., 1989;St Clair et al., 1998;Tomer et al., 2007;Verreyt et al., 2011;Erro et al., 2013;Poletti et al., 2013;Pellicano et al., 2015). Different cross-sectional studies explored this topic both in drug naïve and medicated PD patients at different disease stages, yielding mixed results. ...
Background: Attention is crucial to voluntary perform actions in Parkinson’s disease (PD), allowing patients to bypass the impaired habitual motor control. The asymmetrical degeneration of the dopaminergic system could affect the attentional functions.
Objective: To investigate the relationship between the asymmetric dopaminergic degeneration and the attentional resources in Parkinsonian patients with right-side (RPD) and left-side (LPD) motor symptoms predominance.
Methods: 50 RPD, 50 LPD, and 34 healthy controls underwent visual (V), auditory (A), and multiple choices (MC) reaction time (RTs) tasks. For PD patients, these tasks were performed before and after a 4-week intensive, motor-cognitive rehabilitation treatment (MIRT). The effectiveness of treatment was evaluated assessing Unified Parkinson’s disease Rating Scale (UPDRS) III and Timed-up and Go Test (TUG).
Results: RTs did not differ between PD patients and healthy controls. Before MIRT, no differences between LPD and RPD patients were observed in RTs (p = 0.20), UPDRS III (p = 0.60), and TUG (p = 0.38). No differences in dopaminergic medication were found between groups (p = 0.44 and p = 0.66 before and after MIRT, respectively). After MIRT, LPD patients showed a significant reduction in MC RTs (p = 0.05), V RTs (p = 0.02), and MC-V RTs. A significant association between changes in RTs and improvements in UPDRS III and TUG was observed in LPD patients.
Conclusion: attention does not differ among RPD patients, LPD patients and healthy controls. Only LPD patients improved their performances on attentional tasks after MIRT. We argue that the increased early susceptibility of the left nigrostriatal system to degeneration affects differently the cognitive modifiability and the neuroplastic potential. Our results could provide insight into new therapeutic approaches, highlighting the importance to design different treatments for RPD patients and LPD patients.
... It has been suggested that laterality corresponds to type of cognitive impairment. A comprehensive review indicated there is a compelling suggestion that cognitive domain specific deficits are related with lateralized motor symptoms (Verreyt, Nys, Santens, & Vingerhoets, 2011;Amick, Grace, & Chou, 2006;Schendan, Amick, & Cronin-Golomb, 2009;Cubo et al., 2010) but results are mixed (see Bentin, Silverberg, & Gordon, 1981;Direnfeld, Albert, & Volicer, 1984;Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989). Right side onset PD correlates with worse verbal fluency, object naming, and verbal memory. ...
Objective:
A 71-year-old (MN) with an 11-year history of left onset tremor diagnosed as Parkinson's disease (PD) completed longitudinal brain magnetic resonance imaging (MRI) and neuropsychological testing. MRI scans showed an asymmetric caudate nucleus (right < left volume). We describe this asymmetry at baseline and the progression over time relative to other subcortical gray, frontal white matter, and cortical gray matter regions of interest. Isolated structural changes are compared to MN's cognitive profiles.
Method:
MN completed yearly MRIs and neuropsychological assessments. For comparison, left onset PD (n = 15) and non-PD (n = 43) peers completed the same baseline protocol. All MRI scans were processed with FreeSurfer and the FMRIB Software Library to analyze gray matter structures and frontal fractional anisotropy (FA) metrics. Processing speed, working memory, language, verbal memory, abstract reasoning, visuospatial, and motor functions were examined using reliable change methods.
Results:
At baseline, MN had striatal volume and frontal lobe thickness asymmetry relative to peers with mild prefrontal white matter FA asymmetry. Over time only MN's right caudate nucleus showed accelerated atrophy. Cognitively, MN had slowed psychomotor speed and visuospatial-linked deficits with mild visuospatial working memory declines longitudinally.
Conclusions:
This is a unique report using normative neuroimaging and neuropsychology to describe an individual diagnosed with PD who had striking striatal asymmetry followed secondarily by cortical thickness asymmetry and possible frontal white matter asymmetry. His decline and variability in visual working memory could be linked to ongoing atrophy of his right caudate nucleus.
... Clinical studies have investigated the relationship between the motor laterality and non-motor manifestations. However, these studies have reported inconsistent results; poor cognition in left-onset PD [14], the relation between right-side symptoms and cognition [15], or no differences between the LPD and RPD [16]; greater anxiety and depression in LPD [17] or severe psychosis in extreme RPD [4]; and no consistent relation between motor laterality and non-motor symptoms other than psychosis [4]. These findings suggest that lateralized brain changes must be considered in the study of non-motor symptoms. ...
Background:
Recently, non-motor symptoms of Parkinson's disease (PD) have been considered crucial factors in determining a patient's quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.
Methods:
Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.
Results:
The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).
Conclusions:
These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD.
... Other studies have shown a relationship between lateralization of PD symptoms and hemisphere specific cognitive dysfunction. Several studies reported that predominant right-sided parkinsonian symptoms (reflecting left-hemisphere dysfunction) correlate with impaired performance on verbal fluency and verbal memory, (Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989;Spicer, Roberts, & LeWitt, 1988;Starkstein et al., 1987;Taylor, Saint-Cyr, & Lang, 1986). Left-sided symptoms have been associated with visuospatial impairments (Direnfeld et al., 1984;Finali, Piccirilli, & Rizzuto, 1994) and mild left hemispatial neglect (Starkstein et al., 1987). ...
The current study examined cognitive effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients. Neuropsychological evaluations were conducted at baseline and follow-up. Data was collected from 28 unilateral STN DBS patients (15 English- and 13 Spanish-speaking), and 15 English-speaking matched PD control patients. English-speaking DBS patients demonstrated significant declines in verbal fluency and attention/executive function, whereas PD control patients did not experience significant cognitive decline. Cognitive performance did not differ based on side of DBS. Spanish-speaking DBS patients experienced significant declines in verbal fluency, confrontational naming and visuospatial abilities. Among Spanish-speaking DBS patients, older age and later age of disease onset predicted verbal fluency decline, even after controlling for education.
... Some investigations have supported that RHO is associated with depression (Cole et al., 1996;Leentjens, Lousberg, & Verhey, 2002). Other investigations have found no difference in depression between LHO and RHO patients (Aarsland et al., 1999;Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989;Katzen, Levin, & Weiner, 2006). However, a relationship has been reported between increasing severity of depression and decreased striatal dopamine transporter availability in the left anterior putamen in patients with PD (Weintraub et al., 2005). ...
Objective: Previous research has examined the neurocognitive effects of depression in Parkinson’s disease (PD), finding worse performance on tests of cognitive functioning in PD patients with depression as compared to those without depression. However, this research has not considered the effect of side of onset of motor symptoms. Hence, we sought to investigate the interaction between depression and side of onset on working memory in patients with PD. Method: A total of 66 patients with PD completed the Digit Span Backward subtest of the Wechsler Memory Scale–III as well as two other tests of executive functioning. Groups of left hemibody onset (LHO) with and without depression and right hemibody onset (RHO) with and without depression were created. Results: The results indicated significantly lower performance on the measure of working memory for the LHO with depression group, relative to both the LHO without depression and the RHO with depression groups. Conclusion: These findings indicate that working memory is worse in patients with LHO of motor symptoms who are also depressed, and they suggest that this group of patients might experience greater disability and lower quality of life.
... Las formas de apraxia que han sido relacionadas con la demencia o que es posible que aparezcan en el curso de la enfermedad son las apraxia del vestido, ideomotoras, ideatorias, constructivas y buco-faciales (Hart y Semple, 1990). Según Huber, Freidengerg y Shuttleworth (1989); Le Gall, Truelle y Joseph (1990), los errores más frecuentes se observan en la pantomima y en la copia de gestos. ...
El objetivo de este trabajo es estudiar la relación entre los rendimientos en diferentes tareas práxicas y el grado de perfusión cerebral por Tomografía computarizada por emisión de fotón único (SPECT), a fin de poder realizar una aproximación a la realidad funcional a través de la evaluación clínica neuropsicológica. La muestra está compuesta por 54 sujetos de ambos sexos, diagnosticados con demencia tipo Alzheimer probable siguiendo los criterios del Neuroepidemiology Branch of the National Institute of Neurological and Comunicative Disorders and Stroke y Alzheimer¿s Disease and Related Disorders Association. La evaluación de las praxias ha sido realizada utilizando diferentes modalidades. Las imágenes por SPECT cerebral fueron realizadas mediante gammacámara de la casa Elscint modelo 409-AG. El Radiofármaco utilizado fue, Hexamethylpropylene amine oxime (HMPAO). Los rendimientos obtenidos en todas las tareas práxicas evaluadas, excepto en praxias bucofaciales, guardan relación con los déficits de perfusión cerebral, considerando que la SPECT cerebral mide la repercusión de las alteraciones metabólicas neuronales en la perfusión cerebral.
... Our data did not reveal a relationship between the lateralization of motor signs and alexithymia in PD patients. Although we cannot exclude that the effect of the dopaminergic therapy may have masked possible differences between the two subgroups as for the side of prevalent motor involvement, it should be noted that a failure to demonstrate a relationship between severity and0or lateralization of motor symptoms and tasks investigating cognitive and affective functioning has been previously reported (Huber et al., 1989;St. Clair et al., 1998). ...
There are recent reports that alexithymia may be associated with brain dysfunction involving frontal lobes or right hemisphere regions. However, little is known about the relationship between alexithymia and cognitive deficits in Parkinson's disease (PD). The authors investigated the neuropsychological correlates of alexithymia in a population of 70 nondemented PD patients and 70 controls. Alexithymia was screened using the 20-item version of the Toronto Alexithymia Scale (TAS-20). Standardized scales that measure verbal episodic memory, executive functions, abstract reasoning, and visual-spatial and language abilities were adopted. PD patients with alexithymia performed worse than both PD patients without alexithymia and controls with or without alexithymia on tasks requiring visual-spatial processing. Moreover, regression analyses showed that, in PD patients, but not in controls, poor performance on a constructional praxis task predicted high scores on the TAS-20 subscale, which assesses difficulty in identifying emotions. These data evidence an association between alexithymia and visual-spatial processing alterations in PD patients, supporting the view that the right hemisphere could be specifically involved in the modulation of some facets of alexithymia.
... Others found widespread cognitive deficits in participants with worse left-sided dysfunction while participants with worse rightsided dysfunction were relatively cognitively spared (Direnfeld et al., 1984; Tomer, Levin, & Weiner, 1993). Still others found no cognitive differences in regard to motor asymmetry (Barber, Tomer, Sroka, & Myslobodsky, 1985; Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989; St. Clair, Borod, Sliwinski, Cote, & Stern, 1998) or suggest that type, rather than side, of predominant or initial motor manifestation is the most important factor (Riklan, Stellar, & Reynolds, 1990; Zetusky & Jankovic, 1985). Some of this work was limited by use of non-specific or poorly validated tasks, small sample sizes or participants in varied stages of disease progression. ...
Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be more impaired by PD-related changes in the right side of the brain than in the left. PD (n=35) and control (n=28) participants performed the SDR task. PD participants either had worse motor deficits on the right (RPD) or left (LPD) side of the body. Some participants also had magnetic resonance imaging for measurement of their substantia nigra (SN) volumes. The LPD group performed worse on the SDR task than the RPD and control groups. Right SN volume accounted for a unique and significant portion of the variance in SDR error, with smaller volume predicting poorer performance. In conclusion, left motor dysfunction and smaller right SN volume are associated with poorer spatial memory.
Contrary findings notwithstanding, the prevailing notion is that recognition memory is little affected by Parkinson's disease (PD). Both a power analysis and a meta-analysis were conducted to help clarify the degree of recognition memory deficit associated with PD. The power analysis confirmed that, in general, memory studies of PD participants have been underpowered. This analysis indicated the need to pool study results in a subsequent meta-analysis, the main finding of which was that recognition memory deficits do occur with PD. The largest deficit occurs in PD participants with dementia. Nevertheless, deficits also occur in PD participants without dementia on medication, but nondopaminergic central nervous system abnormalities are more likely to underlie this deficit than PD medication itself. Future development of a theory of cognitive dysfunction in PD should take into account these recognition memory deficits, which may increase with disease progression.
Introduction
Neuroendocrine tumours(NETs) are an uncommon group of heterogenous neoplasms that originate from neuroendocrine cells. Patients with NETs frequently experience diarrhoea that can impact their quality of life. Approximately 20% develop carcinoid syndorme characterised by dry flushing and diarrhoea but causes other than functional syndromes may not be considered. Pancreatic enzyme insufficiency(PEI), bile acid diarrhoea(BAD) and small intestinal bacterial overgrowth(SIBO) are potential causes. There is limited data on prevalence of these conditions in NETs. The main aim of this study is to evaluate the prevalence of PEI, BAD and SIBO in a heterogeneous population of NET patients and secondarily to assess the impact of these conditions on quality of life.
Methods
This was a retrospective, single centre observational study in a dedicated NET. 257 patients were included in this study. PEI was defined as low faecal elastase or treatment with pancreatic enzyme replacement therapy. BAD was defined as an abnormal SeHCAT scan or treatment with bile acid sequestrants. SIBO was defined as a positive hydrogen breath test or empirical antibiotics. The EORTC QLQ-GI.NET21 and a modified Gastrointestinal Symptom Rating Scale(GSRS) questionnaires were completed as part of normal clinical practice. Total scores of the questionnaires of those with and without a diarrhoeal condition were compared.
Results
The majority of patients had a midgut primary (n=202;78.6%), were Grade 1 (n=182;70.8%) and had metastatic disease(n=211;82.1%). Most were on somatostatin analogues(SSAs) (n=186;72.4%) and had surgery(n=175;68.1%). PEI was diagnosed in 153(59.5%) patients with a significant association with the use of SSAs (p<0.001). BAD was diagnosed in 52(20.2%) patients with a significant association with bowel resection (p<0.001). SIBO was diagnosed in 42(16.3%) patients. 163(63.8%) patients had at least one of PEI, BAD or SIBO. of these, 107(65.9%) had a single diagnosis, 29(17.7%) had two diagnoses and 27(16.5%) had three. The median total EORTC QLQ-GINET21 and GSRS scores were significantly higher in those with PEI, BAD or SIBO (p<0.001).
Conclusions
We provide the first systematic study to assess the common causes of diarrhoea in a NET population. PEI, BAD and SIBO are common causes of diarrhoea in patients with NETs. A third of those diagnosed had more than one condition suggesting that if symptoms do not improve with treatment, alongside dose titration an additional cause may need investigation. Ultimately through a stepwise approach to the diagnosis of diarrhoea, symptoms and quality of life of patients may be improved.
Verhaltensstörungen, Depressionen, isolierte kognitive Störungen, pharmakotoxische Psychosen und schließlich dementive Veränderungen werden in zunehmendem Maße bei Parkinson-Patienten beobachtet und mÜssen bei der Behandlung berÜcksichtigt werden. Zur Zeit James Parkinsons stand die Beurteilung der motorischen StÖrung vÖllig im Vordergrund. HÖhere psychische Funktionen — mit Ausnahme von Depressionen, seltenen sensorischen Mißempfindungen und im Finalstadium auftretende delirante Zustandsbilder — wurden im wesentlichen bis zur EinfÜhrung der modernen Anti-Parkinson-Therapie selten und nur am Rande beschrieben. In den letzten hundert Jahren hat sich die durchschnittliche Lebenserwartung in den Industriestaaten nahezu verdoppelt, und es kam zu einer explosionsartigen Zuwachsrate der Hochbetagten von mehreren 100 bis über 1000% (Rückert 1984).
The aim of the paper is to study the relation between the performance obtained in several praxic tasks and the level of brain perfusion with Single Photon Emission Computed Tomography (SPECT) in order to develop an approach to the functional reality with the aid of neuropsychological clinical assessment. The sample consisted of 54 subjects of both sexes, who had been diagnosed Alzheimer-type Dementia following the criteria of the Neuroepidemiology Branch of the National Institute of Neurological and Communicative Disorders and Stroke, and the Alzheimers Disease and Related Disorders Association. Praxia asessment was carried out using different modes. Brain SPECT images were performed using the gammacamera by Elscint, model 409-AG. The radiopharmaceutical used was Hexamethylpropylene amine oxine (HMPAO). Performance obtained in tested, except oral-facial praxis, are asociated with brain perfusion deficits, inasmuch as cerebral SPECT measures the effect of neuronal metabolic alterations in brain perfusion.
Background
We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume.
Methods
Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis.
Results
In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH.
Conclusions
APOE ε4 is associated with increased parietal lobe WMH.
Some research has supported differences in mood functioning in patients with Parkinson's disease (PD) whose motor symptoms begin at the left or right hemibody. Also, a relationship between disease duration and mood disturbances has been reported, but only for PD patients with right hemibody onset. There have been no investigations reported examining the potential interactions between side of onset of motor symptoms, mood, and disease duration on cognitive functioning. Hence, the purpose of this investigation was to determine whether the interaction between mood and disease duration differentially affects cognitive functioning in patients with PD whose motor symptoms begin at the left and right hemibody. A total of 33 PD patients with left hemibody onset and 29 PD patients with right hemibody onset were given a battery of tests to evaluate mood functioning and general cognitive functioning. As predicted, the results indicated that the interaction of disease duration and mood significantly predicted cognitive functioning for PD patients with right hemibody onset of symptoms but not for PD patients with left hemibody onset of symptoms. Interestingly, an unexpected finding was a significant positive relationship between disease duration and energy level for patients with left hemibody onset but not for patients with right hemibody onset. These results indicate that mood problems and disease duration interact to significantly affect cognitive functioning but only for those PD patients who experience a right hemibody onset of symptoms.
Determined to what extent, if any, deficits in verbal reasoning abilities are observed in Parkinson's disease (PD) Ss. 38 PD Ss (mean age 65.1 yrs) and 19 controls participated in a battery of 7 tests, including 2 verbal fluency tests, a lexical test, a similarities test, a validated French version of the California Verbal Learning Test, an invited inference, and a verbal logical reasoning test. While findings do not show generalized impairment in linguistic functions, PD Ss performed poorly on several tasks, suggesting that complex verbal abilities are susceptible to PD. Specifically, tasks requiring algorithmic strategies, in contrast to tasks requiring pragmatic or heuristic approaches, are likely to be associated with impairment in verbal reasoning, deficits in conceptual fluency, and in executive functions underlying language as well as other domains of cognitive function. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Visuospatial abilities play a pivotal role in our daily living. Indeed, our survival depends, to a great extent, on our ability
to navigate sensory space. This means our ability to use spatial maps dependent on visual, tactile, and auditory information
to form and guide motor programs. Visuospatial abilities are complex brain operations requiring integration of occipital,
parietal, and frontal lobe function, as well as the contribution of subcortical structures. Consequently, it is not surprising
that visuospatial skills are often impaired in diseases with movement disorders—an impairment that depends both on the type
and on the stage of the disease in question.
We studied the relationship between two screening cognitive measures and off motor Unified Parkinson's Disease Rating Scale (UPDRS) scores in 108 Parkinson's disease patients. Multiple regressions were conducted to examine the UPDRS subscores' unique contributions to cognitive function. When including bradykinesia, rigidity, and postural/gait instability subscores, only bradykinesia predicted Mini Mental Status Examination (MMSE), normalized beta = -0.57, t(104) = -3.31, P < 0.01, and Dementia Rating Scale-2 (DRS-2), normalized beta = -0.45, t(104) = -2.55, P < 0.05. Tremor was not included in the regression analyses because it did not correlate with cognitive function. When including axial and appendicular subscores, only the axial subscore predicted MMSE, normalized beta = -0.39, t(105) = -3.19, P < 0.01, and DRS-2 scores, normalized beta = -0.40, t(106) = -3.28, P < 0.01. When including left-sided and right-sided subscores, only the right-sided symptoms predicted DRS-2 scores, normalized beta = -0.28, t(105) = -2.45, P < 0.05, and showed a trend toward predicting MMSE scores, normalized beta = -0.22, t(105) = -1.95, P = 0.054. We therefore found that right-sided symptoms (for laterality), axial symptoms (for region), and bradykinesia (for type of symptoms) were the best predictors of cognitive function.
At disease onset, patients with Parkinson's disease (PD) typically report one side of the body to be more affected than the other. Previous studies have reported that this motor symptom asymmetry is associated with asymmetric dopaminergic degeneration in the brain. Research on the cognitive repercussions of this asymmetric degeneration has yielded inconsistent results. Here, we review studies that reported on the cognitive performance of patients with left-sided (LPD) or right-sided (RPD) motor symptom predominance. We present evidence that patients with RPD typically experience problems with language-related tasks and verbal memory, whereas patients with LPD more often perform worse on tasks of spatial attention, visuospatial orienting and memory and mental imagery. In general, no differences were found between both groups on tasks measuring attention and executive function. The association between motor asymmetry and cognitive performance indicates that PD does not lead to one typical cognitive profile. The effect of symptom laterality on the cognitive complaints should be considered in the assessment and treatment of each individual patient.
Depression and anxiety have both been associated with relative left frontal hypoactivation and the motor symptoms of Parkinson's disease typically begin in a lateral or asymmetrical fashion. Hence, PD patients with right hemibody onset may experience heightened depression and anxiety. However, research is mixed regarding whether right or left hemibody onset PD is associated with elevated levels of depression and anxiety. This literature, though, has not considered the potential moderating variable of disease duration. We hypothesized that disease duration would be positively correlated with measures of depression and anxiety in right but not left hemibody onset PD patients. The results indicated that scores on the Geriatric Depression Scale, Beck Depression Inventory-II, and the State Trait Anxiety Scale - State correlated positively with disease duration, but only in the right hemibody onset group of PD patients. Thus, right hemibody onset PD is associated with more severe depressive and anxiety symptoms, but only when disease duration is considered.
In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD.
Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA-motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild-moderate and extreme asymmetry. Predominant LPD or RPD with mild-moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison.
One hundred forty-nine PD patients (74 RPD and 75 LPD) with mild-moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS.
These findings suggest that damage to left-hemisphere plays a disproportionately greater role in PD-related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder.
Thesis (Ph. D.)--Texas Tech University, 1999. Includes bibliographical references (leaves 93-99).
El objetivo de este trabajo es estudiar la relación entre los rendimientos obtenidos en diferentes tareas neuropsicológicas y el grado de perfusión cerebral por Tomografía computarizada por emisión de fotón único (SPECT), en una muestra de 54 sujetos de ambos sexos, diagnosticados con demencia tipo Alzheimer siguiendo los criterios del Neuroepidemiology Branch of the National Institute of Neurological and Comunicative Disorders and Stroke y Alzheimer¿s Disease and Related Disorders Association. Las pruebas neuropsicológicas utilizadas en este trabajo evaluan las siguientes funciones cognitivas: lenguaje, memoria verbal, habilidades visuoespaciales-constructivas, memoria visual, praxias y gnosias digitales. Las imágenes por SPECT cerebral fueron realizadas mediante gammacámara de la casa Elscint modelo 409-AG. El Radiofármaco utilizado fue, Hexametil-Propilen-Amino-Oxina. Los resultados obtenidos nos muestran que existe correlación significativa inversa entre los rendimientos obtenidos en las pruebas neuropsicológicas utilizadas y el grado de perfusión cerebral por SPECT, excepto para las pruebas de recuerdo de un material verbal (lista de palabras) y praxias bucofaciales.
This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.
Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.
Neuropsychological data collected from two groups of patients with idiopathic Parkinson's disease (n = 50, 159) were analysed to investigate the association between presenting motor symptoms determined from retrospective chart review and the risk of cognitive impairment. Presenting motor symptoms were abstracted from the medical records and coded by type, location, and laterality. Longitudinal data on changes in the maximum speed of voluntary arm movements were available for a subsample of patients. Bilateral (v unilateral) presentation was associated with an increased risk of cognitive impairment an average of nine years after onset of disease as measured by memory tests and the mini-mental state examination. A higher rate of decline of arm movement speed was also predictive of greater memory dysfunction. The type, side (left v right), and location (lower v upper extremity) of the presenting symptoms were not, however, consistently associated with the risk of cognitive impairment later in the course of the disease.
Parkinsonians with predominantly unilateral signs provide an interesting experimental means to evaluate if asymmetric nigro-striatal degeneration may affect neuropsychological functions. The aim of our study was to establish if the side of onset of idiopathic Parkinson's disease, right (PDR) or left (PDL), determines a selective pattern of cognitive performances. Furthermore, we verified if PDR and PDL groups show a different frequency of dementia. PDR and PDL patients with at least seven years of disease duration, matched for age, schooling, severity of extrapyramidal symptomatology and index of lateralization, were evaluated by using an extensive neuropsychological battery aimed at assessing hemispheric cognitive asymmetries. Current side of greater motor impairment was the same as the one affected at the onset of the disease.
Only subtle differences in the profile of neuropsychological dysfunction emerged from the comparison of PDR and PDL subjects. Moreover, the number of parkinsonians showing dementia syndrome was the same in both groups. Our results suggest that the side of onset of motor impairment does not significantly influence the cognitive performances in PD. Subcortical anatomic and/or functional asymmetries seem to play a less important role in the intellectual functions than in motor activities.
Controversy surrounds the presence of deficits of visual cognition in Parkinson's Disease. This literature has been seriously undermined by a number of methodological and theoretical faults that make interpretation of this hypothesis difficult. This review proposes a structure of visual cognition composed of 13 aspects. A meta-analysis of these components on 70 studies that used standardised neuropsychological tests and an appropriate normal control group indicates that the PD subjects are significantly compromised on tests of attention and concentration, complex visuospatial functions, and multifactorial spatial functions. More detailed analysis of the basic components of visual cognition was not undertaken due to low statistical power; hence, it remains unclear whether these subjects have primary visual processing deficits in association with their higher order deficits. The observed deficits may be interpreted as being a consequence of either undetermined lower level visual cognitive deficits or a compromise in executive functioning.
Basal ganglia have been known as a motor center because their lesions cause motor disturbances in involuntary movements such as chorea, ballism or akinesia in parkinsonism. The different types of involuntary movements are closely related to the underlying muscle tone. Mechanisms of bradykinesia or akinesia have been elaborated in physiological studies on Parkinson's disease and the significance of sensorimotor processing or attention arousal has been disclosed as a relevant factor of bradykinesia. Analysis of short-stepped gait, frozen gait or apraxia of gait, has claimed the frontal lobe and the striatum to be a locomotion center especially in humans (bipedal locomotion). Cognitive function of the basal ganglia has attracted attention particularly in the disorder of Parkinson's disease. Subcortical dementia, difficulty in formation or changes of concepts are encountered in advanced stages of Parkinson's disease. Whether cognitive functions in the frontostriatal system are primarily related to the motor function of the brain is an issue for future study.
In the present study, fifty-four subjects were tested; twenty-seven with idiopathic Parkinson's disease and twenty-seven normal controls matched in age, education, verbal ability, level of depression, sex and socio-economic status. The subjects were tested on eight tasks. Five of the tasks were the classic deductive reasoning syllogisms, modus ponens, modus tollendo tollens, affirming the consequent, denying the antecedent and three-term series problems phrased in a factual context (brief scripts). Three of the tasks were inductive reasoning, including logical inferences, metaphors and similes. All tasks were presented to subjects in a multiple choice format. The results, overall, have shown nonsignificant differences between the two groups in deductive and inductive reasoning, an ability traditionally associated with frontal lobes involvement. Of the comparisons performed between subgroups of the patients and normal controls concerning disease duration, disease onset and predominant involvement of the left and/or right hemisphere, significant differences were found between patients with earlier disease onset and normal controls and between bilaterally affected patients and normal controls, demonstrating an additive effect of lateralization to reasoning ability.
Eleven patients with Parkinson's disease (PD) and predominantly right-sided motor signs, 12 patients with PD and predominantly left-sided signs, and 11 demographically matched healthy controls were compared on tests assessing a range of cognitive and affective functions. Assuming a novel approach, our test battery was composed of measures drawn from ones previously used in the hemiparkinson' s disease and lateralized PD literature. The two patient groups were similar in illness duration, severity of motor signs, and degree of lateralized motor deficits. Statistical analyses did not reveal significant differences between patient groups, consistent with other studies that have failed to find differences in neuropsychological functioning between PD patients with right- and left-sided motor signs.
The strength and sensitivity of neuropsychological test findings in patients with Parkinson's disease (PD) was reviewed using meta-analytic principles to provide a basis of comparison of deficits in nondemented and demented patients with PD. The review revealed significant relationships among duration of disease, physical disability, and cognitive impairment in nondemented patients, and qualitative and quantitative differences in the pattern of neuropsychological test impairments between nondemented and demented patients with PD. The disparate profiles of neuropsychological impairment in nondemented and demented patients may indeed reflect disease progression in keeping with the significant clinical correlations in nondemented patients. That is, as the duration of the disease endures, it appears that performance on tasks of delayed recall deteriorates first, followed by performance on measures of manual dexterity, cognitive flexibility, and abstraction.
Contrary findings notwithstanding, the prevailing notion is that recognition memory is little affected by Parkinson's disease (PD). Both a power analysis and a meta-analysis were conducted to help clarify the degree of recognition memory deficit associated with PD. The power analysis confirmed that, in general, memory studies of PD participants have been underpowered. This analysis indicated the need to pool study results in a subsequent meta-analysis, the main finding of which was that recognition memory deficits do occur with PD. The largest deficit occurs in PD participants with dementia. Nevertheless, deficits also occur in PD participants without dementia on medication, but nondopaminergic central nervous system abnormalities are more likely to underlie this deficit than PD medication itself. Future development of a theory of cognitive dysfunction in PD should take into account these recognition memory deficits, which may increase with disease progression.
Non-demented patients with Parkinson's disease (PD), especially if they are high functioning and early in the course of their disease, usually exhibit mild deficits in anterograde recall memory for verbal and non-verbal material, visuospatial reasoning, visuomotor construction, temporal ordering and sequencing. Impairments in problem solving and verbal fluency tests may also occur. PD patients with predominantly right-sided symptoms usually exhibit more severe difficulties with verbal than with non-verbal tasks. We report a case of a highly educated right-handed man with very mild right-sided hemiparkinsonism who never received anti-Parkinsonian or other psychoactive medication. Our patient showed anterograde and retrograde amnesia for faces and spatial locations and difficulties on complex visuospatial tasks that required manual responses, but normal to above average performance on all other cognitive tests. The specific pattern of cognitive loss early in PD may depend on which spatial, facial or verbal pre-frontal striatal circuits are deprived of their dopaminergic inputs.
The phenotypic spectrum of PINK1-associated Parkinsonism was studied in a family with homozygous (n = 4) or heterozygous (n = 3) PINK1 mutations. All homozygous mutation carriers were definitely affected; the heterozygous carriers were asymptomatic but displayed unequivocal signs of probable or possible Parkinsonism. This finding suggests a role not only of homozygous but also of heterozygous PINK1 mutations in the development of parkinsonian signs and underlines the necessity to carefully investigate family members of affected mutation carriers.
The investigation is concerned with individual items instead of lists. "Forgetting over intervals measured in seconds was found. The course of retention after a single presentation was related to a statistical model. Forgetting was found to progress at differential rates dependent on the amount of controlled rehearsal of the stimulus. A portion of the improvement in recall with repetitions was assigned to serial learning within the item, but a second kind of learning was also found." (PsycINFO Database Record (c) 2006 APA, all rights reserved).
This study investigates the hypothesis that, as a consequence of Parkinson's disease, disturbed caudate outflow will lead to deficits in cognitive functions dependent upon the integrity of the prefrontal cortex, the cortical focus of caudatofugal signals. Since Parkinson's disease also involves lesions in extrastriatal midbrain cells which reduce the intrinsic supply of dopamine to this cortical region, such functions are at double risk. Forty nondemented parkinsonian patients were drawn from a pool of 100 consecutive patients and matched with 40 normal control subjects according to age, education, IQ, and sex. All patients were quantitatively rated on neurological indices of disease. Neuropsychological assessment of the patient and normal groups included tests of general intelligence, psychomotor skills, memory, visuospatial and executive functions. No global cognitive decline was observed in the parkinsonian group. Moreover, memory and visuospatial abilities were generally intact. A small cluster of deficits emerged, interpreted as reflecting impairment in the ability to spontaneously generate efficient strategies when relying on self-directed task-specific planning. In addition, several tests thought to be sensitive to frontal lobe function distinguished patients with symptoms strongly lateralized to the right versus left side of the body. Deficits in strategic planning were later investigated in relation to severity of disease and to patient attributes including IQ and age, both of which were relevant to performance on specific tasks. Results were compared with previous investigations in parkinsonian patients and discussed from the perspective of both animal and human studies involving damage to the cerebral cortex and basal ganglia. As the prefrontal cortex is thought to play a crucial role in self-directed behavioural planning, the validity of an outflow model in predicting the consequences of caudate nucleus dysfunction was supported.
• We examined the relationship of disease laterality to neuropsychological and neurochemical features in patients with idiopathic Parkinson's disease (PD). We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase. The patients with PD were divided into two groups depending on the side of the body with greater disease involvement. Both parkinsonian groups, those more affected on the left (group L) and those more affected on the right (group R), were otherwise similar in all other clinical and historical features. Group L patients showed greater neuropsychological impairments than group R patients. Group L also had significantly higher CSF levels of homovanillic acid and acetylcholinesterase than group R. These findings of neuropsychological and neurochemical differences between groups L and R suggest functional or anatomic asymmetries of dopaminergic systems in the CNS.
The difficulties inherent in obtaining consistent and adequate diagnoses for the purposes of research and therapy have been pointed out by a number of authors. Pasamanick12 in a recent article viewed the low interclinician agreement on diagnosis as an indictment of the present state of psychiatry and called for "the development of objective, measurable and verifiable criteria of classification based not on personal or parochial considerations, but on behavioral and other objectively measurable manifestations."Attempts by other investigators to subject clinical observations and judgments to objective measurement have resulted in a wide variety of psychiatric rating scales.4,15 These have been well summarized in a review article by Lorr11 on "Rating Scales and Check Lists for the Evaluation of Psychopathology." In the area of psychological testing, a variety of paper-and-pencil tests have been devised for the purpose of measuring specific
Fluency tasks from two categories, animals and words beginning with a specified letter (“C”, “F”, “L”), were administered to normal elderly and to elderly with mild or moderate-to-severe senile dementia of the Alzheimer type. In both tasks, normals were superior to both dementia groups, while the mild dementia group was less impaired. Normals and mild dementia subjects retrieved more animal names than “CFL” words. Compared with normals, mild dementia subjects showed a greater performance decrement on the “CFL” words task than on animal naming. Moderate-to-severe dementia subjects showed no difference between tasks. Results suggest that (1) category structure influences retrieval processes, (2) components of the structure are affected differentially during the disease process.
Eleven alcoholic patients with Korsakoff's disease and 15 control subjects were given three tests of retrograde amnesia. The first consisted of photographs of famous faces from the past, the second was a recall test of famous people and events, and the third was a multiple-choice questionnaire. To determine whether previously reported temporal gradients (ie, preservation of remote events) were related to item difficulty, half of the questions dealt with events of transient fame while half concerned subjects that continued to receive public attention for many years. The findings indicate that alcoholic patients with Korsakoff's disease have a marked retrograde amnesia that is characterized by a steep temporal gradient, and that this gradient is not an artifact due to the difficulty of the questions or the method of testing.
It is now recognized that many patients with Parkinson's disease will experience cognitive and intellectual decline in the course of their illness. Selective visuospatial and memory impairment, executive dysfunction, slowed information processing, and depression are consistently observed in a high proportion of patients. Language abilities appear to be relatively spared. Current age, age of onset, disease duration, and predominant motor symptoms all exert important differential effects on the expression of the dementing process. Although these patterns point to a subcortical origin, it is probable that Parkinson's disease is composed of several dementia syndromes.
Seven dextral patients with Parkinson's disease (PD) who had predominant right-sided motor signs were compared on neuropsychological tests with eight dextral patients with PD who had predominant left-sided signs. Objective criteria for group designation were developed from clinical ratings. The patient subgroups were matched on age, education, estimated premorbid IQ, severity of motor signs, and medication usage. Patients with signs lateralized to the right were more impaired on tests of dominant hemisphere function (serial digit learning, confrontation naming, and verbal associative fluency), but no differences were found on tests of nondominant hemisphere function (form sequence learning, line orientation, facial recognition), indicating some correlation of neuropsychological performance with lateralization of predominant motor signs. Findings demonstrate that the cognitive deficits (particularly visuospatial) previously reported in the literature are not seen consistently in all subjects with PD.
Six cases of adult dementia with mesolimbic pathology are reported. The core clinical syndrome consists of parkinsonism, progressive dementia, and behavioral disturbances (generally depression). The histopathologic findings uniformly include a loss of pigmented neurons in the ventral tegmental area plus neurofibrillary tangles and/or cell loss in the entorhinal cortex and pyramidal cell layer of the hippocampus (perforant pathway). Neuronal depletion in the ventral tegmental area frequently is associated with similar cell loss in the adjacent substantia nigra and in the locus ceruleus. The development of neurofibrillary tangles in the perforant pathway occurs in the absence of senile plaques and is possibly related to diminished dopaminergic input.
In recent years, several attempts have been made to characterize the nature of the cognitive deficits shown by patients with Parkinson's disease. It has been suggested variously that they have difficulty in switching cognitive set, in performing effortful (or controlled) as opposed to automatic tasks, or that their impairment is found in tasks which maximize the amount of 'self-directed task specific planning'. It is proposed that this latter distinction may be reformulated in terms of the degree of internal versus external attentional control which is required by the task. An experiment is described which attempted to manipulate this parameter. A version of the Stroop colour-word test was used, in which the words 'red' and 'green' were presented in the complementary coloured 'ink'. Subjects responded either to the colour of the ink in which the word was written or the colour named by the word. The relevant attribute changed at intervals during the course of the experiment. In one condition, the relevant stimulus attribute was cued before each trial. In another condition, subjects had to remember which attribute was currently relevant. Results revealed that patients with Parkinson's disease were impaired mainly on the second version of the task which required internal attentional control. The results are discussed in relation to the models of Working Memory (Baddeley, 1986), and attentional control (Norman and Shallice, 1980). Exploration of these models leads to the formulation of a theory in which the crucial determinant of cognitive impairment in Parkinson's disease is reduced resources in the Supervisory Attentional System. Provided the demands of the task are within the patient's available attentional resources the patient may not show any deficit. If, however, the attentional demands exceed available resources, as in tasks which depend upon internal cues, then deficits will be observed.
A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject-ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.
The relationship between severity of disease, intellectual impairment, and depression was examined in 50 patients with Parkinson's disease. A significant correlation between severity of disease and intellectual impairment suggests that both may result from the same subcortical lesions. Depression was not significantly related either to severity of disease or to intellectual impairment. This suggests that the relationship between severity of disease and intellectual impairment was not an artifact of increasing depression. Severity of rigidity and of bradykinesia did predict severity of intellectual decline, but severity of tremor predicted better intellectual status. Patients with a predominance of tremor may have a more benign clinical course as well as better intellectual function than patients with a predominance of rigidity and bradykinesia.
Nine parkinsonian patients with main unilateral symptoms on the right side (RHP) and nine with symptoms on the left side (LHP) were assessed through a comprehensive neuropsychological battery. RHP performed at a lower level than LHP on the WAIS verbal subtests. Although both groups scored poorly on a test of frontal lobe functions, RHP performed significantly lower than LHP. On a line bisection task, LHP showed a mild left hemispatial neglect. In conclusion, mild but significant intergroup differences were observed, tending to correlate with predominantly hemispheric functional deficits.
This study investigates the hypothesis that, as a consequence of Parkinson's disease, disturbed caudate outflow will lead to deficits in cognitive functions dependent upon the integrity of the prefrontal cortex, the cortical focus of caudatofugal signals. Since Parkinson's disease also involves lesions in extra-striatal midbrain cells which reduce the extrinsic supply of dopamine to this cortical region, such functions are at double risk. Forty nondemented parkinsonian patients were drawn from a pool of 100 consecutive patients and matched with 40 normal control subjects according to age, education, IQ, and sex. All patients were quantitatively rated on neurological indices of disease. Neuropsychological assessment of the patient and normal groups included tests of general intelligence, psychomotor skills, memory, visuospatial and executive functions. No global cognitive decline was observed in the parkinsonian group. Moreover, memory and visuospatial abilities were generally intact. A small cluster of deficits emerged, interpreted as reflecting impairment in the ability to spontaneously generate efficient strategies when relying on self-directed task-specific planning. In addition, several tests thought to be sensitive to frontal lobe function distinguished patients with symptoms strongly lateralized to the right versus left side of the body. Deficits in strategic planning were later investigated in relation to severity of disease and to patient attributes including IQ and age, both of which were relevant to performance on specific tasks. Results were compared with previous investigations in parkinsonian patients and discussed from the perspective of both animal and human studies involving damage to the cerebral cortex and basal ganglia. As the prefrontal cortex is thought to play a crucial role in self-directed behavioural planning, the validity of an outflow model in predicting the consequences of caudate nucleus dysfunction was supported.
Electromyographic reaction times of the left and the right finger extensor muscles in extension movement of the wrist were examined in 42 patients with Parkinson's disease, and 20 normal subjects. Compared to the normal subjects and the patients with neurological signs confined to the right side, the patients with neurological signs on the left side or on both sides showed slowing of reaction times regardless of the side of responding hand. The patients with asymmetry of bilateral neurological signs showed slower RTs on the more affected side.
The performance of patients with Parkinson’s disease was compared with that of controls on two types of tests of motor ability: repetitive tapping of a button for a ten-second period of time and tracking a light moving at random on a screen. The performance of patients with parkinsonism was significantly worse than the controls on both types of tests. The response to the tests differed, however, depending on whether the patient’s major motor symptoms predominated on the left or right side of the body or were equal on both sides of the body. Patients with primarily right-sided symptoms (inferred left hemispheric dysfunction) had bimanual alterations in both the tapping and the tracking tasks. Patients with primarily left-sided symptoms (inferred right hemispheric dysfunction) performed significantly worse than the controls on the tapping test, only with the hand contralateral to the major brain damage. However, in the tracking task, where a visuospatial factor was required, the group with left-sided symptoms (right hemispheric dysfunction) was more impaired. The findings are discussed in relation to asymmetries of cerebral function produced as a result of subcortical disease.
Previous studies in patients with parkinsonism revealed alterations in their ability to judge their own "postural vertical" with vision excluded. To assess the significance of this finding and its relationship to underlying pathology, further studies of spatial orientation were carried out. The performance of 47 Parkinsonian patients was compared with that of 32 controls on a route-walking test previously used by SEMMES et al. (1955). It was found that the total parkinsonian group was significantly worse than the controls in their ability to guide themselves through space according to pattern as specified by a visual map. Further, when the patients were subdivided into three groups according to the laterality of their major parkinsonian symptoms, it was found that they reacted differentially to the test. Those with primarily right-sided symptoms did not differ in their performance from the controls, whereas those with left-sided symptoms or those with approximately equal symptoms on both sides of the body performed significantly worse.
Tyrosine hydroxylase was used to identify catecholaminergic neurons in the substantia nigra and ventral tegmental area of the human mesencephalon. High enzyme activity in the normal ventral tegmental area indicated the presence of numerous cathecholaminergic neurons, most likely dopamine cells. Tyrosine-hydroxylase activity was decreased in the ventral tegmental area of parkinsonian patients, implying a lesion of the mesocortical dopamine system in Parkinson disease.
We examined the relationship of disease laterality to neuropsychological and neurochemical features in patients with idiopathic Parkinson's disease (PD). We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase. The patients with PD were divided into two groups depending on the side of the body with greater disease involvement. Both parkinsonian groups, those more affected on the left (group L) and those more affected on the right (group R), were otherwise similar in all other clinical and historical features. Group L patients showed greater neuropsychological impairments than group R patients. Group L also had significantly higher CSF levels of homovanillic acid and acetylcholinesterase than group R. These findings of neuropsychological and neurochemical differences between groups L and R suggest functional or anatomic asymmetries of dopaminergic systems in the CNS.
We investigated the role of perceptual and motor factors in visuospatial impairment in 30 patients with Parkinson's disease (PD) and 30 matched controls. All subjects were administered visuospatial tests, which included "visuoperceptual" tasks, requiring minimal motor responses, and "visuomotor" tasks. The performance of patients with PD was considerably impaired on several tasks from both groups, and this impairment was not related to depression or intellectual impairment. Patients in stage 3 of the disease tended to show the greatest impairment. Those in stage 1 (unilateral symptoms), however, tended to show more impairment than those in stage 2.
To determine the prevalence of depression in Parkinson disease (PD) we evaluated 55 consecutive patients without dementia and 31 of their spouses. All subjects completed the Beck depression inventory and a quantitative mini-mental state examination. Using the Beck criteria, 47% of the patients and 12% of the spouses rated themselves as significantly depressed. Mental state scores were significantly lower in the patients. There was a correlation between the severity of depression and cognitive impairment, particularly for calculation, digit span, and visuomotor skills. The severity of parkinsonism, particularly bradykinesia, also paralleled cognition. There was a slight but significant relationship between parkinsonism and depression. These results confirm the high incidence of depression in PD, and suggest that depression in Parkinson patients may be accompanied by mild intellectual impairment and inattention which is independent of the severity of the illness.
We studied 60 patients with idiopathic Parkinson disease with motor and neuropsychologic tests to ascertain whether the severity of motor symptoms was associated with the degree of neuropsychologic deficity. Significant correlations were found between the severity of brady kinesia and impaired performance on tests assessing visual-spatial reasoning and psychomotor speed. More severe tremor was associated with better performance on a spatial orientation memory test. There relationships remained when age, age at onset, and self-rated depression were controlled. The findings suggested that cognitive impairment may result from the same subcortical lesions that cause motor symptoms.
Articulatory disturbances are frequently described in Parkinson disease, but language disorders are not. We have occasionally encountered parkinsonian patients with word-finding difficulty unrelated to memory loss, intellectual impairment, or dysarthria. To examine this, 22 medically stable parkinsonian patients were given the vocabulary subtest of the WAIS, the Boston Naming Test, measures of verbal fluency, and sentence repetition. Signs and symptoms of parkinsonism were rated. WAIS vocabulary subtest scores were above the mean for normal aged subjects, but confrontation naming was one standard deviation below norms for age and education. Naming was facilitated by cues in most patients. Only sentence repetition correlated with dysarthria. Category naming was impaired and correlated significantly with the severity of parkinsonism, especially bradykinesia. This suggests that a type of anomia may occur in Parkinson disease. it shares the clinical characteristics of the "tip-of-the-tongue" phenomenon and "word production anomia" seen in some aphasics.
Patients with Parkinson's disease and patients with dementia showed greater deterioration on functions attributed to the right cerebral hemisphere, than on functions attributed to the left. Relative to matched controls, Parkinson patients were significantly impaired on right hemisphere tests, but did not differ on left hemisphere tests. Demented patients were significantly deficient on all tests, but right decline was greater than left. Ninety-six patients were tested: 32 diagnosed as senile or presenile dementia, 32 Parkinson patients, and 32 non-neurological patients matched for age, sex and education. Functional performance was assessed by a battery of validated tests for left and right hemisphere cognitive functions. Patients were defined with two scores based on the results of the test: Cognitive Laterally Quotient (CLQ) reflecting the averaged performance on the left hemisphere tests, subtracted from the average performance on right hemisphere tests, and Cognitive Performance Quotient (CPQ), reflecting the total level of performance of both hemispheres. These measures defined a characteristic cognitive profile for each group.
The Mental Status Examination in Neurorology. Philadelphia: F.A. Davis Frontal lobe dysfunction in Parkinson's disease: The cortical focus of neostriata! outflow
- R L Strub
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- A Lange
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Parkinsonism: onset, progression, and mortality Relationship of motor symptoms, intellectual impairment, and .depression in Parkinson's disease Is the mesocortical dopaminergic system involved in Parkinson's disease KERTESZ, A. The Western Aphasia Battery
- M M Hoehn
- M D Yahr
- S J Huber
- G W Paulson
- E C Shuttleworth
- Y Agid
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Relationship of motor symptoms to intel-lectual deficits in Parkinson's disease Short-term retention of individual verbal items Verbal fluency in aging and dementia Neuropsychological performance in lateralized par-kinsonism
- J A Mortimer
- F J Pirozzolo
- E C Hansch
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Brain dopamine and the syndromes of Parkinson and Huntingon
- Bernheimer