Figure - available from: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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Corneal nerve fiber morphology in a subject with no cognitive impairment, mild cognitive impairment (MCI), and dementia. Corneal confocal microscopy (CCM) images of the sub‐basal nerve plexus from a subject with (A) no cognitive impairment, (B) MCI, and (C) dementia showing decreased corneal nerve fiber density, length, and branch density in subjects with MCI and dementia compared to subjects with no cognitive impairment
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Introduction:
This study compared the capability of corneal confocal microscopy (CCM) with magnetic resonance imaging (MRI) brain volumetry for the diagnosis of mild cognitive impairment (MCI) and dementia.
Methods:
In this cross-sectional study, participants with no cognitive impairment (NCI), MCI, and dementia underwent assessment of Montreal...
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Background
Parkinson’s disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with di...
Mild cognitive impairment (MCI) precedes the Alzheimer’s disease (AD) continuum, making it crucial for therapeutic care to identify patients with MCI at risk of progression. We aim to create generalized models to identify patients with MCI who advance to AD using high-dimensional-data resting state functional magnetic resonance imaging (rs-fMRI) br...
Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Ja...
Objective:
The objective of this study was to assess the performance of combining MRI-based texture analysis with machine learning for differentiating sepsis-associated encephalopathy (SAE) from sepsis alone.
Method:
Sixty-six MRI-T1WI images of an SAE patient and 125 images of patients with sepsis alone were collected. Frontal lobe, brain stem,...
Aim. To determine whether adolescents with type 1 diabetes (T1D) have morphological changes of the corneal nerve fibers and reduced smell and taste function compared to healthy control subjects as a sign of cranial nerve affection and to evaluate possible associated risk factors for cranial nerve affection. Methods. The study was a part of the T1DA...
Citations
... To be more specific, studies have shown that the morphological changes in mild cognitive impairment (MCI) brain amyloidosis include distinctive spatial patterns that are highly susceptible to AD pathology, such as the central pre-gyrus [14], the entorhinal cortex [15], the right inferior frontal gyrus [16], the insula [17], the posterior cingulate gyrus [18,19], the temporoparietal cortex [20], the hippocampus [21][22][23], and the thalamus [24]. Additionally, in accordance with a recent clinical follow-up study identifying atrophy in subregions of the amygdala as a potential marker for future progression to CI [25], a subregion of the amygdala was included in our Rad marker, emphasizing the involvement of the amygdala in the early development of AD [26,27] (Fig. 2). All the above discussion provided additional explanations as to why Rad carries the highest AUC. ...
To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer’s disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model’s performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor.
... 8,9 Both large-medium (Aα/β) fiber and small (Aδ and C) fiber damage have been demonstrated in PD. 10,11 Large fiber dysfunction has been attributed to levodopa therapy, while small fiber neuropathy is thought to be intrinsic to the neurodegenerative process in PD. [11][12][13] Corneal confocal microscopy (CCM) is an in vivo ophthalmic imaging technique that has been widely used to quantify corneal nerve damage in a range of peripheral neuropathies and central neurodegenerative diseases. 14,15 Indeed, CCM has a high sensitivity in detecting small fiber loss in mild PD, 16 and we have previously shown that corneal nerve fiber loss was associated with the severity of cognitive and motor dysfunction, 17 as well as autonomic dysfunction. 18 Recently, a longitudinal study by Lim et al. 19 showed that greater corneal nerve loss was associated with more rapid motor progression in a cohort of patients with PD. ...
... The present findings add to the growing body of data showing corneal nerve fiber loss in a range of neurodegenerative diseases, including dementia, 15,37 amyotrophic lateral sclerosis, 38 Friedreich's ataxia, 39 multiple sclerosis, 40,41 and PD. [16][17][18][19] Indeed, progressive corneal nerve fiber loss is evident in subjects with mild cognitive impairment (MCI) and dementia, 15 and is associated with cognitive dysfunction and functional independence. 37 Corneal nerve fiber loss has also been reported in patients with amyotrophic lateral sclerosis and related to disease severity. ...
Background
Parkinson’s disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes.
Objective
The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes.
Methods
Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated.
Results
Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm ² , 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm ² , 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm ² , 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832.
Conclusion
Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.
... More recently, Ponirakis assessed the relationship between corneal nerve morphometry and MRI brain volumetry and cognitive performance in MCI and dementia. After adjusting for potential confounders, he discovered cognitive impairment was related to corneal nerve fiber density, length, branch density, whole brain, hippocampus, cortical gray matter, thalamus, amygdala, and ventricle volumes [106]. ...
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder impacting cognition, function, and behavior in the elderly population. While there are currently no disease-modifying agents capable of curing AD, early diagnosis and management in the preclinical stage can significantly improve patient morbidity and life expectancy. Currently, the diagnosis of Alzheimer’s disease is a clinical one, often supplemented by invasive and expensive biomarker testing. Over the last decade, significant advancements have been made in our understanding of AD and the role of ocular tissue as a potential biomarker. Ocular biomarkers hold the potential to provide noninvasive and easily accessible diagnostic and monitoring capabilities. This review summarizes current research for detecting biomarkers of Alzheimer’s disease in ocular tissue.
... It has recently shown great promise to detect early neurodegeneration in MCI and dementia, even more reliably than magnetic resonance imaging (MRI) [14,88,89] and has been proposed as a tool to longitudinally measure and objectively assess the effectiveness of novel drug treatments in clinical trials [90]. CCM has been shown to have superior diagnostic capability for MCI compared to brain volumetry [91], and can predict progression from MCI to dementia, comparable to hippocampal and whole brain volumetry [92]. In light of these recent promising findings from Qatar, we sought to investigate whether HCPs in the region were aware of this upcoming modality. ...
Dementia is characterized by progressive cognitive decline, memory impairment, and disability. Alzheimer's disease (AD) accounts for 60-70% of cases, followed by vascular and mixed dementia. Qatar and the Middle East are at increased risk owing to aging populations and high prevalence of vascular risk factors. Appropriate levels of knowledge, attitudes, and awareness amongst health care professionals (HCPs) are the need of the hour, but literature indicates that these proficiencies may be inadequate, outdated, or markedly heterogenous. In addition to a review of published quantitative surveys investigating similar questions in the Middle East, a pilot cross-sectional online needs-assessment survey was undertaken to gauge these parameters of dementia and AD among healthcare stakeholders in Qatar between 19 April and 16 May 2022. Overall, 229 responses were recorded between physicians (21%), nurses (21%), and medical students (25%), with two-thirds from Qatar. Over half the respondents reported that >10% of their patients were elderly (>60 years). Over 25% reported having contact with >50 patients with dementia or neurodegenerative disease annually. Over 70% had not undertake related education/training in the last 2 years. The knowledge of HCPs regarding dementia and AD was moderate (mean score of 5.3 ± 1.5 out of 7) and their awareness of recent advances in basic disease pathophysiology was lacking. Differences existed across professions and location of respondents. Our findings lay the groundwork for a call-to-action for healthcare institutions to improve dementia care within Qatar and the Middle East region.
... 13 We have previously shown evidence of corneal nerve loss in participants with MCI and dementia and demonstrated that CCM had a better diagnostic capability for identifying people with MCI compared to MRI brain volumetry. [14][15][16] Furthermore, corneal nerve fiber loss was associated with the severity of cognitive dysfunction and functional independence 16 as well as cerebral ischemia in patients with MCI and dementia. 7 This study compared the ability of CCM with brain volumetry in identifying participants with MCI who progress to dementia. ...
... We previously reported 44% mixed AD with vascular lesions, 32% AD, and 24% vascular dementia (VaD) in a cohort aged 73.4 years. 14 Several risk factors for dementia, [5][6][7][8][9]14 including age, vascular disease, diabetes, hypertension, obesity, dyslipidemia, and sleep deprivation may limit the diagnostic accuracy of biomarkers for AD. 7,10,11 Cortical and subcortical ischemia, risk factors for dementia, are associated with corneal nerve loss, brain atrophy, and cognitive deficits in MCI and dementia. ...
Objectives:
This study compared the utility of corneal nerve measures with brain volumetry for predicting progression to dementia in individuals with mild cognitive impairment (MCI).
Methods:
Participants with no cognitive impairment (NCI) and MCI underwent assessment of cognitive function, brain volumetry of thirteen brain structures, including the hippocampus and corneal confocal microscopy (CCM). Participants with MCI were followed up in the clinic to identify progression to dementia.
Results:
Of 107 participants with MCI aged 68.4 ± 7.7 years, 33 (30.8%) progressed to dementia over 2.6-years of follow-up. Compared to participants with NCI (n = 12), participants who remained with MCI (n = 74) or progressed to dementia had lower corneal nerve measures (p < 0.0001). Progressors had lower corneal nerve measures, hippocampal, and whole brain volume (all p < 0.0001). However, CCM had a higher prognostic accuracy (72%-75% vs 68%-69%) for identifying individuals who progressed to dementia compared to hippocampus and whole brain volume. The adjusted odds ratio for progression to dementia was 6.1 (95% CI: 1.6-23.8) and 4.1 (95% CI: 1.2-14.2) higher with abnormal CCM measures, but was not significant for abnormal brain volume.
Interpretation:
Abnormal CCM measures have a higher prognostic accuracy than brain volumetry for predicting progression from MCI to dementia. Further work is required to validate the predictive ability of CCM compared to other established biomarkers of dementia.
... Recently, a study by Ponirakis et al. revealed that the diagnostic capability of corneal confocal microscopy compared to brain volumetry is higher for identifying MCI and comparable for dementia. However, abnormalities in both brain volumetry and corneal confocal microscopy are associated with cognitive impairment (Ponirakis et al., 2022). ...
Objective
There is a shred of growing evidence demonstrating that diabetic patients are at higher risk of developing Alzheimer's disease compared to the general population. The previous investigation showed the protective effect of metformin for delaying dementia in diabetic patients. However, there are limited data on the effect of metformin on structural changes. This study aims to investigate the effect of metformin on hippocampal and cortical volumes in non-demented diabetic individuals.
Method
We entered 157 non-demented diabetic subjects including 89 mild cognitive impairment (MCI), and 68 cognitively healthy individuals from Alzheimer's disease Neuroimaging Initiative (ADNI) which were then categorized as metformin users and non-users. We used the ANCOVA model for measuring the association between metformin use and hippocampal and cortical volumes.
Results
Among 157 subjects with a mean age of 71.8 (±7.7) included in this study, 76 individuals were stratified as metformin users. Results of the univariate model indicate that metformin users had a higher right (p = 0.003) and left parietal lobe volume (p = 0.004). Moreover, the volume of left cingulate was higher in those who used metformin compared to those not used it (p = 0.027). Our results were also significant for the right frontal lobe and indicated that metformin users had higher volume (p = 0.035). There were no significant differences in the hippocampus, occipital, and temporal regions.
Conclusion
Our findings showed the protective effects of metformin on brain volumes in non-demented elderly individuals with diabetes. Comparing the groups show strong enough results regarding the lower atrophy in metformin users.
