Brain pathological mechanism of weight loss preceding incident mild cognitive impairment

Abstract

AbstractBackgroundWeight loss in late life is associated with a higher risk of dementia and higher mortality. However, the temporal and etiological associations between weight loss and mild cognitive impairment (MCI) remain unclear.MethodWe examined 709 Alzheimer’s Disease Neuroimaging Initiative participants to investigate body mass index (BMI) trajectories preceding the progression from normal cognition to MCI (N‐t‐M progression), and to explore the association between brain pathology and BMI trajectories preceding incident MCI.ResultDuring N‐t‐M progression, participants developed multiple brain pathologies, and amyloid β (Aβ) accumulation in the frontotemporal region at baseline was associated with decreased BMI (Figure 1, false discovery rate‐corrected p<0.05). For pathological changes, participants had increased accumulation of Aβ and tau, accelerated hypometabolism, and decreased gray matter volume in the brain during N‐t‐M progression. More importantly, accelerated hypometabolism (p<0.001) and gray matter atrophy (p = 0.011) were associated with a rapid decline in BMI during N‐t‐M progression.ConclusionThese findings highlight the importance of regular monitoring of weight changes in older adults as faster BMI decline and lower BMI may be the result of brain pathology and associated with rapid progression of pathology, and provide a theoretical basis for strategies to minimize weight loss to prevent or delay MCI onset.