journal articles
HYPOLIPIDEMICS REDUCE THE RATE OF ALZHEIMER\'S DISEASE DEVELOPMENT AND DEMENTIA PROGRESSION: A COHORT STUDY LINKED WITH GENETIC AND NEUROPATHOLOGICAL ANALYSES
Zohi Sternberg, Rebecca E. Podolsky, Jihnhee Yu, Shuangcheng Hua, Stanley Halvorsen, Bernhard J. Schaller
BACKGROUND: High cholesterol contributes to the development and progression of dementia due to both Alzheimer's disease (A.D.) and vascular pathology. However, the effects of lipid-lowering regimen (LLR) on cognitive dysfunction and brain neuropathology are unknown.
OBJECTIVE: To investigate the effect of LLR on the conversion from normal to mild cognitive impairment (MCI), indicated by CDR-SOB of >0–2.5 (MCI), and the progression to dementia, indicated by CDR-SOB =>3 (10-year follow-up) and LLR effect on the rate of survival (15-year follow-up). Participants were stratified by age (≤70 years and >70 years), gender, and the presence of at least one copy of the APOE4 allele. We also analyzed the effect of LLR on brain neuropathology in participants, indicated by Braak staging, hippocampal atrophy, and CSF levels of total Tau. The differential effect of LLR, with or without cerebrovascular disease, lacunar infarct, or cystic infarction in the cognitive network, was analyzed.
METHODS: We have analyzed the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS).
RESULTS: In participants with CDR-SOB of >0–2.5, the use of hypolipidemic agents was associated with a reduced yearly increase in the CDR-SOB scores by 0.0088 (0.0038, 0.0138) unit (P < 0.001). This effect was more pronounced in participants with CDR-SOB =>3 showing a reduced yearly increase in the CDR-SOB scores by 0.1733 (0.1441, 0.2025) unit (P < 0.001) in LLR-users compared to non-users, and an increased rate of survival [HR: 0.822 (0.746, 0.906). P = 0.001]. The pattern persisted when participants were stratified based on age, gender, and the presence of APOE4. LLR had no significant effect on Braak staging scores, hippocampal atrophy, and total CSF Tau level, and was independent of the presence or absence of cerebrovascular disease, lacunar infarct, and cystic infarction in cognitive network.
CONCLUSION: Our results have implications for delaying cognitive dysfunction and halting the progression of dementia, regardless of the etiology being related to AD or vascular pathology.
CITATION:
Zohi Sternberg ; Rebecca E. Podolsky ; Jihnhee Yu ; Shuangcheng Hua ; Stanley Halvorsen ; Bernhard J. Schaller (2025): Hypolipidemics reduce the rate of Alzheimer's disease development and dementia progression: A cohort study linked with genetic and neuropathological analyses. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100555