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 (A beta 42), cerebrospinal fluid (CSF) A beta 1-42, 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 A beta 42, and low CSF A beta 1-42, moderated by age, APOE epsilon 4, and baseline tau levels. AL may interact with age and genetic risk, impacting AD biomarkers and MCI progression.