P1‐246: Association between cholesterol exposure and neuropathological findings: The adult changes in thought study
Year: 2015
Type: article
Study design: Observational Study
Abstract: Hyperlipidemia is an important risk factor for the development of cognitive impairment and has been linked with dementia in epidemiological studies. We sought to characterize the relationship between cholesterol exposure and neuropathological outcomes from a community-based study. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting randomly selected non-demented people aged ≥65 from a healthcare delivery system. HDL and non-HDL lab values from Group Health computerized records were used, and APOE status was obtained. Autopsy consent rates are 25-30%. We evaluated the following outcomes: Braak stage; CERAD grade; amyloid angiopathy; presence of cystic infarcts; presence of any microinfarcts, cerebral microinfarcts, and deep microinfarcts; presence of any Lewy bodies and Lewy bodies in the substantia nigra or locus ceruleus, frontal or temporal cortex, and in the amygdala. Using linear mixed models with age and antilipemic medication as predictors, we obtained predicted cholesterol values at age 70 for individuals with available cholesterol data between ages 65-75 years. We then evaluated whether the predicted cholesterol level at age 70 was associated with neuropathological outcomes controlling for age at death (range: 71-99), APOE, gender, and their interactions when appropriate. 525 decedents came to autopsy by 8/2014. Of these, 446 (85%) had available cholesterol data over the course of their life, with APOE genotyping and lab values between 65-75 years available for 289 (55%). Logistic regression results are summarized in the Table. Notably, an association was observed between predicted non-HDL cholesterol at age 70 and Lewy body pathology, specifically in the substantia nigra or locus ceruleus and frontal or temporal cortex. Our study suggests an association between non-HDL cholesterol exposure and Lewy body pathology, independent of APOE status. No associations were observed between cholesterol levels and neuropathological indices used to characterize Alzheimer's disease pathology, vascular pathology, or atrophy. Although the majority of research on cholesterol and neurodegenerative diseases has emphasized Alzheimer's disease outcomes, burgeoning evidence suggests that lipids play a role in regulating alpha-synuclein aggregation. Future studies are needed to elucidate whether mid- to late-life cholesterol exposure has a mechanistic role in Lewy body pathology.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2495945837