Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia.

A consistent amount of evidence suggests that vascular factors might be involved in the pathogenesis of late onset Alzheimer's disease (LOAD). We evaluated the presence of endothelial dysfunction by measuring the plasma levels of soluble E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in a sample of patients affected by LOAD (n. 60) or vascular dementia (VD: n. 80). They were compared with a sample of older patients with cerebrovascular disease but not-dementia (CDND: n. 40), and with a sample of healthy older controls (n. 30). sVCAM-1 plasma levels were higher in LOAD and VD compared with controls. Among patients (LOAD, VD, and CDND), sE-selectin levels were higher in individuals with most severe cerebrovascular disease on CT scan. At multivariate regression analysis, fasting glucose (p<0.05) and TNF-alpha levels (p<0.02) were positively correlated with sE-selectin levels (adjusted r(2): 20%), while sVCAM-1 was positively correlated with age (p<0.01), and alcohol consumption (p: 0.03), and negatively associated with HDL-C levels (p: 0.005), (p<0.01; adjusted r(2): 44%), independent of possible confounders. Increased sVCAM-1 plasma levels in LOAD and VD suggest the existence of endothelial dysfunction in both types of dementia. The possible role of E-selectin in the pathogenesis of cerebrovascular disease is also supported by our data.

Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia.

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.

High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia.

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross-sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6, Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p < 0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple regression analysis, IL-6 was associated with BI in the whole sample and in VD, but not in LOAD, independent of age, gender, smoking, alcohol consumption, hypertension, diabetes, coronary heart disease, previous stroke, and mini mental state examination score. Our study suggests the existence of an independent and negative relationship between IL-6 plasma levels and functional status in older individuals with vascular dementia. This finding might contribute to explain the 'excess of disability' phenomenon described in older demented patients.

Leukoaraiosis is associated with functional impairment in older patients with Alzheimer's disease but not vascular dementia.

BACKGROUND: Leukoaraiosis (LA) is a common finding in older persons, and might be associated with reduced cognitive performance, gait abnormalities, and functional impairment. Although LA is more frequent in persons affected by dementia, scant data are available about its clinical consequences in this group of patients. OBJECTIVE: To study the association between presence of LA and functional performance in basic activities of daily living in a sample of older persons affected by dementia. DESIGN: We conducted a cross-sectional study on 214 patients; 77 affected by late onset Alzheimer's disease (LOAD), and 137 by vascular dementia (VD). Functional status was assessed using Barthel Index (BI). LA was assessed using computed tomography. RESULTS: In LOAD patients, LA (OR: 7.87; 1.26-48.94), and MMSE score (OR: 0.83; 0.71-0.98) were associated with the risk of severe disability, independent of age, gender, diabetes, hypertension, coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and brain atrophy. In VD patients, MMSE score (OR: 0.77; 0.64-0.93), and CHD (OR: 7.41; 1.09-50.21), but not LA (OR: 2.07; 0.45-9.45) were associated with a severe functional impairment after multivariate adjustment. CONCLUSIONS: Our study suggests that LA might be associated with a worse functional status in basic activities of daily living in patients affected by LOAD but not VD. LA might act synergistically with cognitive and behavioural disturbances to the onset and progression of disability of these patients.

Genetic polymorphisms in older subjects with vascular or Alzheimer's dementia.

OBJECTIVES: Paraoxonase, angiotensin-converting enzyme (ACE), methylenetetrahydrofolate reductase (MTHFR), and apo E gene polymorphisms were evaluated in older patients with vascular dementia (VD) or late-onset Alzheimer's disease (LOAD). MATERIAL AND METHODS: Sixty patients with VD, 45 patients with LOAD, and 54 non-demented controls were compared. RESULTS: No differences in the distribution of paraoxonase, ACE, and MTHFR polymorphisms were found. The overall frequency of apo E epsilon4 allele was "low"; epsilon4 allele was more frequent in LOAD (17.5%) and VD (13.3%) compared with controls (9.2%), but the difference was not statistically significant. CONCLUSION: Paraoxonase, ACE, and MTHFR polymorphisms were not associated with VD or LOAD; these common polymorphisms might have a marginal role in the pathogenesis of dementia in older subjects. In spite of a "low" frequency of the apo E epsilon4 allele in our sample, the frequency of epsilon4 allele was about double in LOAD compared with controls.

Lipoprotein profile in older patients with vascular dementia and Alzheimer's disease.

BACKGROUND: Some alterations of the lipoprotein profile have been associated with cerebrovascular disease. Recently, it has been suggested that cerebrovascular disease might play a role in the pathogenesis of both vascular dementia (VD) and Alzheimer's disease (AD). Nevertheless, the possible association of dyslipidemias with VD or AD is still a controversial issue. METHODS: We investigated the lipoprotein profile in 100 older patients with vascular dementia (VD; no degrees: 60) or Late Onset Alzheimer's Disease (LOAD; no degrees: 40). The patients were compared with 54 community dwelling non-demented older controls. RESULTS: After adjustment for functional status, blood sedimentation rate, and serum albumin levels, no differences in lipoprotein profile emerged between the three groups, with the exception of HDL-C that was lower in VD compared with controls. Low HDL-C (< 45 mg/dL) was associated with VD (O.R.: 6.52, C.I. 95%: 1.42-30.70 vs controls, and 4.31, C.I. 95%: 0.93-19.82 vs LOAD), after multivariate adjustment. No differences in plasma lipid levels emerged between the three groups after stratification for apo E4 genotype. CONCLUSIONS: In this cross-sectional study low HDL-C levels are associated with VD, but not with LOAD, in a sample of older subjects.

Alzheimer disease and vascular dementia: relationships with fasting glucose and insulin levels.

Cerebrovascular disease and Alzheimer disease are the leading causes of dementia in elderly subjects. In spite of it, relatively little is known about the pathogenesis and risk factors for dementia. We evaluated fasting plasma glucose and insulin, albumin, lipids, Lp(a) and uric acid levels in nondiabetic patients of both sexes affected by vascular dementia (VD) and senile dementia of the Alzheimer type (SDAT) as well as in a control group of age-matched nondemented subjects. Following a covariance analysis by gender, body mass index, albumin levels and prevalence of arterial hypertension, total and LDL cholesterol as well as HDL cholesterol levels were not significantly different among the three groups. Fasting glucose (p < 0.001 and p < 0.005, respectively) and insulin levels (p < 0.05 for both differences) were higher in patients with VD and SDAT than in control subjects. Our data show that nondiabetic patients with VD or SDAT have higher fasting glucose and insulin levels than healthy control subjects. These metabolic characteristics were not influenced by differences in gender, adiposity, nutritional status, lipids or presence of arterial hypertension.