2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Insulin-Resistance

To examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by. This observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [. An amyloid-positive PET scan was found in 33.3% of the IR- group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1-8.9,. These results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.

Topics: Aged; Aging; Amyloid; Aniline Compounds; Apolipoprotein E4; Brain; Cross-Sectional Studies; Female; Follow-Up Studies; Genotype; Heterozygote; Humans; Insulin Resistance; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles

Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD.. Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal).. In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition.. This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.

Topics: Aged; Amyloid; Aniline Compounds; Apolipoproteins E; Body Mass Index; Brain; Female; Humans; Hyperglycemia; Imaging, Three-Dimensional; Insulin Resistance; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Thiazoles

Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.. To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain β-amyloid burden, measured with carbon 11–labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy.. Scores calculated from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study.. Prospective, serially assessed cohort of community-dwelling subjects.. Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography.. Autopsy and 11C-PiB positron emission tomography.. The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses.. We found no significant correlations between measures of brain AD pathology or 11C-PiB β-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole.. In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Aniline Compounds; Baltimore; Benzothiazoles; Cognition Disorders; Female; Glucose Intolerance; Humans; Insulin Resistance; Longitudinal Studies; Male; Prospective Studies; Radionuclide Imaging; Thiazoles