Allostatic load dynamics, Alzheimer's disease biomarkers, and progression in individuals with mild cognitive impairment: findings from the Alzheimer's Disease Neuroimaging Initiative.

Allostatic load (AL), reflecting chronic stress, is linked to cognitive decline, but its role in the Alzheimer's disease (AD) continuum needs further study. We examined the relationship between AL, progression from mild cognitive impairment (MCI) to mild dementia due to AD, and AD biomarkers. We analyzed 385 MCI individuals over 36 months using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. AL index (ALI) changes over 12 months were calculated using plasma neuroendocrine, immunological, and metabolic markers. AD biomarkers included plasma amyloid beta 42 (Aβ42), cerebrospinal fluid (CSF) Aβ1-42, tau, and hippocampus volume. A one-point ALI increase was associated with MCI conversion odds by 15%. ALI increased in those progressing to mild dementia due to AD and decreased in MCI stable participants. ALI increases were linked to high CSF tau, plasma Aβ42, and low CSF Aβ1-42, moderated by age, APOE ε4, and baseline tau levels. AL may interact with age and genetic risk, impacting AD biomarkers and MCI progression.

Highlights: ALI increase raises MCI to AD conversion odds by 15%.ALI increases in those progressing to AD and decreases in stable participants.Higher ALI was linked to high CSF tau, plasma Aβ42, and low CSF Aβ1-42These associations were moderated by age, APOE ε4 status, and baseline CSF tau.