2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Vascular-Diseases

There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit.. The study included two groups of patients with probable AD dementia with evidence of the AD pathophysiologic process: 24 patients with age at onset <60 years old and 36 patients with age at onset >70 years old. Amyloid deposition was assessed using carbon-11-labeled Pittsburgh compound B positron emission tomography, comorbid SVD was assessed using magnetic resonance imaging, and neuronal metabolic deficit was assessed using fluorodeoxyglucose positron emission tomography. Group differences of global and regional distribution of pathology were explored using region of interest and voxel-based analyses, respectively, carefully controlling for the influence of dementia severity, apolipoprotein E genotype, and in particular SVD. The pattern of cognitive impairment was determined using z scores of the subtests of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery.. Patients with late-onset AD showed a significantly greater amount of SVD. No statistically significant differences in global or regional amyloid deposition or neuronal metabolic deficit between the two groups were revealed. However, when not controlling for SVD, subtle differences in fluorodeoxyglucose uptake between early-onset AD and late-onset AD groups were detectable. There were no significant differences regarding cognitive functioning.. Age at onset does not influence amyloid deposition or neuronal metabolic deficit in AD. The greater extent of SVD in late-onset AD influences the association between neuronal metabolic deficit and clinical symptoms.

Topics: Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Apolipoproteins E; Benzothiazoles; Brain; Female; Fluorodeoxyglucose F18; Humans; Male; Metabolic Diseases; Middle Aged; Radionuclide Imaging; Thiazoles; Vascular Diseases

The objective of this study was to define whether vascular risk factors interact with β-amyloid (Aβ) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD).. Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Aβ was assessed using [(11)C]Pittsburgh compound B-PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index.. Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of Aβ. These frontotemporal regions are also affected in individuals with Aβ deposition, but the latter show additional thinning in parietal cortices. Aβ and vascular risk were found to interact in posterior (especially in parietal) brain regions, where Aβ has its greatest effect. In this way, the negative effect of Aβ in posterior regions is increased by the presence of vascular risk.. Aβ and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Chi-Square Distribution; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Risk Factors; Thiazoles; Vascular Diseases

The relationship between the apolipoprotein E ε4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer's disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(-) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79-2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70-11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54-7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Brain; Cognition Disorders; Female; Genotype; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Fibers, Myelinated; Neuropsychological Tests; Prospective Studies; Radionuclide Imaging; Thiazoles; Vascular Diseases