Association Between Late-Life Weight Change and Dementia: A Population-based Cohort Study

Abstract

Background The impact of late-life weight changes on incident dementia is unclear. We aimed to investigate the associations of body mass index (BMI) and weight changes with dementia and to explore the role of APOE ɛ4 in these associations. Methods A total of 1,673 dementia-free participants aged ≥60 years were followed for an initial 6 years to detect changes in BMI/weight and then for an additional 6 years to detect incident dementia. BMI change ([BMIfirst 6-year follow-up - BMIbaseline] / BMIbaseline) was categorized as stable (≤5%), and moderate (5–10%) or large (>10%) gain or loss. Weight change (weightfirst 6-year follow-up - weightbaseline) was categorized as stable (≤2.5 kg), and moderate (2.5–7.5 kg) or large (>7.5 kg) gain or loss. Dementia was diagnosed following standard criteria. Data were analyzed using Cox regression models. Results Over the second 6-year follow-up period, 102 incident dementia cases were identified. Compared with stable BMI, the hazard ratios (95% CI) of dementia were 2.61 (1.09−5.54) and 2.93 (1.72−4.91) for BMI gain or loss >10%, respectively. The risk of dementia was higher among APOE ɛ4 carriers experiencing a large BMI gain (9.93 [3.49−24.6]) or loss (6.66 [2.83−14.4]) than APOE ɛ4 non-carriers with stable BMI. Similar results were observed for weight change and dementia associations. Conclusions BMI and weight changes showed U-shaped associations with dementia risk. Large body weight gain and loss alike are associated with an almost 3-fold higher risk of dementia, which may be amplified by APOE ɛ4.

Associations of body habitus and its changes with incident dementia in older adults

“…[23][24][25] There are also theories suggesting that the associations between being underweight or undergoing weight loss, and lower dementia risk are due to reverse causality. 15,16,26 In line with this speculation are the attenuated associations over time, among the participants who were underweight at baseline and those whose BMI or WC decreased. The early neuropathological changes during the prodromal phase of dementia may influence body weight before the manifestation of cognitive symptoms.…”

“…Our results demonstrating that weight gain is associated with dementia add to the few studies that investigated this. 15,16,44 Apart from the cardiovascular risk, weight gain contributes to homeostatic imbalance and cellular dysfunction via certain pathways (e.g., insulin resistance), which leads to neuronal damage. 16,45,46 However, the impact of elevated BMI on dementia has been observed to flip across the life course being detrimental in earlier life but protective after the age of 70.…”

“…Consistent with our findings, weight loss in older age has been documented as a risk factor for dementia in prior literature. 6,15,16 The mechanisms remain unclear, but one plausible explanation points to the common pathologies shared by cognitive impairment and weight loss, such as malnutrition and frailty. [20][21][22] These conditions may result in a decrease in body weight and meanwhile, adversely affect cognitive function.…”

“…BMI change and WC change were grouped into stable (within ±5%), increase (>5%), or decrease (<À5%), aligning with the cut-offs used in previous literature. [15][16][17]…”

Neuro-Adipokine Crosstalk in Alzheimer’s Disease

“…An association between late-life weight loss and the development of MCI is found independent of midlife body weight [ 36 ]. Interestingly, recent data suggest that both substantial late-life weight gain and weight loss are associated with a higher risk of dementia [ 37 ]. Hence, it is plausible that significant shifts in either direction of the body weight set point leads to a decline in brain health due to improper compensatory mechanisms.…”