2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Cerebrovascular-Disorders

To determine whether vascular and neurodegenerative factors influence cognition before clinically relevant Alzheimer disease pathology, we analyzed MRI measures and amyloid imaging in an ethnoracially diverse cohort of cognitively normal individuals older than 60 years.. Participants (n = 154; mean age 74.15 ± 6.94; 50% female; 54% Caucasian, 22.1% Hispanic, 14.9% African American) were recruited from the University of California, Davis Alzheimer's Disease Research Center, who were cognitively normal at baseline, time of PET, and MRI, and received yearly cognitive assessment for 6.23 ± 4.16 years. Mixed model regression with random slope and intercept was calculated for episodic memory and executive function, adjusting for age, sex, education, and ethnicity.. Vascular burden score was associated with total white matter hyperintensity (WMH) volume (β, 0.171; 95% confidence interval [CI], 0.024-0.318). WMH volume was associated with low baseline executive function (-0.115; -0.226 to -0.003) and rate of change in memory (-0.029; -0.045 to -0.012). Hippocampal volume was associated with the rate of change in memory (0.040; 0.021-0.059) and executive function (0.024; 0.008-0.039). Continuous measures of amyloid status influenced change in memory (-0.026; -0.044 to -0.008) and executive function (-0.033; -0.046 to -0.021) independently of MRI measures.. Vascular brain injury and neurodegeneration are associated with baseline cognitive performance and the rate of longitudinal change independent of amyloid status among community-dwelling, ethnicity diverse cognitively normal individuals, supporting the role of vascular diseases as risk factors for later-life dementia.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Brain; Cerebrovascular Disorders; Cognition; Cognitive Dysfunction; Disease Progression; Executive Function; Female; Hippocampus; Humans; Independent Living; Magnetic Resonance Imaging; Male; Memory Disorders; Memory, Episodic; Neuropsychological Tests; Organ Size; Plaque, Amyloid; Positron-Emission Tomography; Thiazoles; White Matter

We investigated the independent effects of Alzheimer's disease (AD) and cerebrovascular disease (CVD) pathologies on brain structural changes and cognition.. Amyloid burden (Pittsburgh compound B [PiB] retention ratio), CVD markers (volume of white matter hyperintensities [WMH] and number of lacunae), and structural changes (cortical thickness and hippocampal shape) were measured in 251 cognitively impaired patients. Path analyses were utilized to assess the effects of these markers on cognition.. PiB retention ratio was associated with hippocampal atrophy, which was associated with memory impairment. WMH were associated with frontal thinning, which was associated with executive and memory dysfunctions. PiB retention ratio and lacunae were also associated with memory and executive dysfunction without the mediation of hippocampal or frontal atrophy.. Our results suggest that the impacts of AD and CVD pathologies on cognition are mediated by specific brain regions.

Topics: Aged; Aged, 80 and over; Amyloid; Aniline Compounds; Atrophy; Brain; Cerebrovascular Disorders; Cognition Disorders; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Retrospective Studies; Thiazoles

Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories ad

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloid beta-Peptides; Analysis of Variance; Aniline Compounds; Cerebrovascular Disorders; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Predictive Value of Tests; Thiazoles; Tomography Scanners, X-Ray Computed

Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Brain; Cerebrovascular Disorders; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Neuropsychological Tests; Positron-Emission Tomography; Thiazoles

Topics: Aniline Compounds; Carbon Radioisotopes; Cerebral Arteries; Cerebral Cortex; Cerebral Hemorrhage; Cerebrovascular Disorders; Echocardiography, Three-Dimensional; Female; Fibrinolytic Agents; Heart Atria; Heart Neoplasms; Humans; Intracranial Embolism; Magnetic Resonance Imaging; Middle Aged; Myxoma; Peripheral Vascular Diseases; Positron-Emission Tomography; Predictive Value of Tests; Thiazoles; Tissue Plasminogen Activator; Treatment Outcome