Barbara Vallotti's research while affiliated with University of Florence and other places

Functional decline is a core feature of dementia, but its relationship with cognitive impairment is not always predictable. In the present study, we looked for the cognitive and non-cognitive determinants of the functional status in subjects with Alzheimer's disease (AD) and vascular dementia (VD). We studied 85 patients referred to our outpatient clinic: 44 affected by AD and 41 by VD (NINCDS-ADRDA, and NINDS-AIREN criteria, respectively). Cognitive impairment was measured with mini mental state examination (MMSE) and with an extended neuropsychological battery; functional impairment with Barthel index (BI), basic activities of daily living (BADL) and instrumental activities of daily living (IADL); comorbidity with index of disease severity (IDS). Depressive symptoms were evaluated by the geriatric depression scale (GDS), behavioral disorders by the UCLA neuropsychiatric inventory (NPI). The two groups were matched for gender, age, educational level, MMSE, GDS and NPI. VD patients compared to AD showed a lower BI, a greater comorbidity, a more frequent presence of neurological gait disorders at the physical examination and a lower score at the tasks assessing selective attention and verbal fluency. In the multivariate analysis, measures of selective attention and of picture naming, together with the presence of neurological gait disorders, were independently related to BI. In our case-mix, VD patients were more disabled than those with AD, in spite of the same MMSE score, and showed more severe attentional defects.

The aging process determines several modifications of the kidney, that, however, do not provoke any dysfunction in normal conditions. But in the elderly--in the presence of stressful situations and particularly when adrenergic activation is present--the kidney is more vulnerable than in the young, and renal failure may arise. Variations typical of the aging kidney are accelerated when hypertension overlaps the physiological renal process, because both senescence and hypertension weight on the same structures, i.e. glomeruli. We studied renal hemodynamic adaptation capacity both in the healthy elderly and in patients affected by isolated systolic hypertension, in an acute experiment which requires the application of a mental stress-induced adrenergic activation. In hypertensive patients we have already demonstrated a total lack of renal adaptation capacity. In fact, while the elderly normotensives react with a prolonged and pronounced vasoconstriction, in those with isolated systolic hypertension, adrenergic activation induces a passive renal vasodilation and glomerular hyperfiltration. The anomalous adaptation capacity of renal hemodynamics is probably due to an impairment in the paracrine response of renal vasculature. Indeed in the hypertensive elderly, unlike in the normotensive one, no variations of autacoid production occur during the adrenergic activation. Following on from this, pattients affected by isolated systolic hypertension passively suffer the many hypertensive peaks which characterize their every day life. The altered renal autoregulation of the elderly with isolated systolic hypertension may explain the accelerated glomerulosclerosis and the greater incidence of renal damage and end-stage renal disease which characterize this condition. These aspects underline the primary role of the antihypertensive treatment of isolated systolic hypertension, not only for the prevention of cardiovascular mortality but also of renal damage and/or end-stage renal disease.

The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.

The aim of this study was to evaluate the renal response in the elderly with isolated systolic hypertension (ISH) when an adrenergic activation, as induced by mental stress, is applied. Renal hemodynamics and kidney neurohumoral response to mental stress were studied in 8 elderly patients with ISH (aged 63 to 82 years) along with 8 elderly normotensive subjects. The study encompassed four 30-minute experimental periods (baseline, mental stress, and recovery I and II). In these patients, the mental stress-induced blood pressure rise was associated with a significant increase in both effective renal plasma flow ((131)I-labeled hippurate clearance) and glomerular filtration rate ((125)I-labeled iothalamate clearance) (+42% and +29%, respectively; P<0.01 for both), without variations in filtration fraction, while elderly normotensives reacted to adrenergic stimulation with renal vasoconstriction but with the glomerular filtration rate constant. Variations in renal vasoactive substances, which paralleled hemodynamics of the kidney, differed in the 2 groups. In normotensives, excretion (radioimmunoassay) of endothelin-1, prostaglandin E(2), and cGMP increased during the stimulus (+50%, +54%, and +59%, respectively; P<0.05). In ISH patients the release of these autacoids did not vary in any of the experimental periods. In conclusion, in patients with ISH the renal adaptive capacity to sympathetic activation is impaired, and the data may suggest that the glomerulus passively suffers the blood pressure increase, probably because of the insufficiency of the neurohumoral response, particularly in regard to the increase of endothelin-1. This hemodynamic pattern may predispose ISH patients to a higher risk of renal injury.

Lack of insight or impaired awareness of deficits in patients with dementia is a relatively neglected area of study. The aim of this study was to evaluate insight in a group of demented patients with two assessment scales and to assess their relationship with the cognitive level of disease severity. Sixty-nine consecutive patients affected by Alzheimer's disease (n = 37) and vascular dementia (n = 32) with a wide range of cognitive impairment (MMSE = 17.0 +/- 6.4) were recruited. Insight was evaluated with the Guidelines for the Rating of Awareness Deficits (GRAD)--specifically targeted to memory deficits--and the Clinical Insight Rating scale (CIR), evaluating a broader spectrum of insight (reason for the visit, cognitive deficits, functional deficits, and perception of the progression of the disease). In the whole sample, GRAD and CIR were significantly associated with MMSE (Spearman's coefficient = .51, p < .001; and r = -.55, p < .001) and with Clinical Dementia Rating scale (-.57, p < .001; and r = .57, p < .001) respectively. The shape of the relationship of MMSE with CIR and GRAD scales was assessed with spline smoothers suggesting that the relationship follows a trilinear pattern and is similar for both scales. Insight was uniformly high for MMSE scores > or = 24, showed a linear decrease between MMSE scores of 23 and 13, and was uniformly low for MMSE scores < or = 12. The trilinear model of the association between insight and cognitive status reflects more closely the observable decline of insight and can provide estimates of when the decline of insight begins and ends.

The adaptive capacity of the aging kidney to stimulation of the sympathetic nervous system, as induced by a 30-minute mental stress (MS), was assessed in 8 elderly healthy women (68 to 82 years of age) and compared with that of 8 younger women (24 to 40 years of age). The study encompassed 4 consecutive 30-minute periods (baseline, mental stress, recovery 1, and recovery 2). In the elderly subjects, baseline effective renal plasma flow (ERPF)(iodine 131-labeled hippurate clearance) was lower and glomerular filtration rate (GFR)(iodine 125-labeled iothalamate clearance) was proportionally less reduced than in the younger group; the filtration fraction (FF) was higher. The elderly group excreted more endothelin 1 (ET-1) (P < .05), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1alpha (6-keto PGF1alpha)(P < .001 for both)(radioimmunoassay). Mental stress induced similar increases in blood pressure, heart rate, and plasma catecholamines in the 2 age groups, limited to the stimulation period. In the elderly group, mental stress caused a prolonged decrease in ERPF that reached its maximum 60 minutes after mental stress (-33%, P < .05), while GFR remained constant during the whole experiment, so that FF increased. In the younger subjects, renal hemodynamic changes were limited to the mental stress period. ET-1 increased during mental stress and the first recovery period in the elderly group (+50% and +25%, P < .05) as it did in the younger group, but the elderly group differed from the younger in that vasodilating prostaglandins increased only during mental stress. In conclusion, the aging kidney reacts to adrenergic stimulation with more-pronounced and -prolonged vasoconstriction that is probably caused by a defect in prostaglandin modulation of endothelin activity. Autoregulation of GFR is maintained at the expense of increased intraglomerular pressure.

The aging kidney is characterized by both anatomical and functional changes. However, renal modifications that are currently observed in the elderly are often due not only to the physiological renal senescence but also to the overlapping of various pathological conditions that may be subclinical or unrecognized. Therefore the present chapter will deal with the consequences of physiological aging of the kidney and the reasons will be examined why these modifications in the elderly are capable of conditioning a different reaction in the presence of a stressful or pathological situation in respect to the young.

The aim of this study was to define the neurohumoral response associated with the renal hemodynamic perturbations induced by mental stress acting as an adrenergic stimulus. In 8 healthy women, the effects of mental stress were studied during four consecutive 30-minute periods (baseline, mental stress, recovery I, recovery II). Mental stress induced sympathetic activation as evidenced by increases in blood pressure, heart rate, and plasma norepinephrine level. Effective renal plasma flow (iodine 131-labeled hippurate clearance) decreased only during mental stress (-22%, p < 0.05 vs baseline); glomerular filtration rate (iodine 125-labeled iotalamate clearance) remained constant during the entire experiment; the filtration fraction increased significantly during mental stress and recovery I (+30% and +22%, respectively, p < 0.02 for both). Complex neuroendocrine responses were associated with the hemodynamic changes. Urinary excretion of endothelin-1 and 6-keto-PGF(1alpha) increased during mental stress (+53%, p < 0.01, and +20%, p < 0.01, respectively) and recovery I (+49% and +29%, respectively, p < 0.01 for both). Urinary cyclic guanosine monophosphate rose only during mental stress (+77%, p < 0.05), whereas excretion of PGE2 showed a stepwise increase throughout recovery I and II (+292%, p < 0.01, and +360%, p < 0.001, respectively). In conclusion, the present experiments demonstrate that renal hemodynamic response induced by mental stress is a complex reaction in which endothelin-1, prostaglandins, and presumably nitric oxide take part.

Renal formation of the vasoconstrictor prostaglandins thromboxane A2 (TXA2 ) and prostaglandin F2α (PGF2α ) was investigated in 25 patients with cardiac failure, divided into New York Heart Association functional classes I to IV, and in eight healthy control subjects. Plasma renin activity (PRA) and hemodynamic parameters were also investigated. Renal vasoconstrictor eicosanoid formation, measured in urinary daily excretion, was not different between patients in class I and control subjects. Class II to IV patients showed progressively increasing production of PGF2α (F = 49.8, p < 0.001, analysis of variance) and TXA2 (F = 37.8, p < 0.002). PGF2α excretion peaked in class IV (+1266% vs class I, p < 0.001). Compared with class I, urinary excretion of thromboxane B2 was +816% in class III and +1561% in class IV (both p < 0.001). PRA was significantly increased only in class IV (+1558%, p < 0.001). The current results indicate a progressive increase in renal production of vasoconstrictor eicosanoids directly related to New York Heart Association class and suggest that these prostanoids may have a role in deterioration of renal function. (Am Heart J 1997;133:94-100.)