Adiposity in the older population and the risk of dementia: The Rotterdam Study

Abstract

Introduction:We determined associations of total and regional adiposity with incident dementia among older adults. Methods: Within the population-based Rotterdam Study, adiposity was measured as total, android, and gynoid fat mass using dual-energy X-ray absorptiometry in 3408 men and 4563 women, every 3 to 6 years between 2002 and 2016. Incident dementia was recorded until 2020.Results: Higher adiposity measures were associated with a decreased risk of dementia in both sexes. After excluding the first 5 years of follow-up, only the association of gynoid fat among women remained significant (hazard ratio 0.85 [95% confidence interval 0.75-0.97] per standard deviation increase). No major differences in trajectories of adiposity measures were observed between dementia cases and dementia-free controls.Discussion: Higher total and regional fat mass related to a decreased risk of dementia. These results may be explained by reverse causality, although a protective effect of adiposity cannot be excluded.

Weight loss and risk of dementia in individuals with versus without obesity

“…Furthermore, adiposity itself may have a role in protection against dementia risk. A recent prospective study showed that high adiposity in older adults predicted a reduced risk of dementia 15 . The neuroprotective role of hormones such as leptin or estrogen could be suggested for this finding 1,37 .…”

“…3,4 However, opposite results have also been reported in studies of older adults (see Supplementary Table 1). Longitudinal cohort studies have observed that obesity or high body mass index (BMI) at age 65 or older is associated with decreased risk of dementia, [5][6][7][8][9][10][11][12][13][14][15] yielding the concept of the "obesity paradox." 7 In addition to the reverse relationship between obesity and dementia, several longitudinal cohort studies have reported that weight began to fall 6-10 years before diagnosis of dementia, [16][17][18][19][20] leading to the proposal of weight loss as a prodromal sign of dementia.…”

“…However, opposite results have also been reported in studies of older adults (see Supplementary Table 1). Longitudinal cohort studies have observed that obesity or high body mass index (BMI) at age 65 or older is associated with decreased risk of dementia, 5–15 yielding the concept of the “obesity paradox.” 7 In addition to the reverse relationship between obesity and dementia, several longitudinal cohort studies have reported that weight began to fall 6–10 years before diagnosis of dementia, 16–20 leading to the proposal of weight loss as a prodromal sign of dementia 21 . A recent prospective cohort study with BMI trajectory and brain autopsy supported this suggestion, revealing that individuals with a higher burden of AD pathology underwent steeper BMI loss before death than those with a lower burden 22 …”

Associations of blood cell indices and anemia with risk of incident dementia: A prospective cohort study of 313,448 participants

“…Third, we re-modeled by excluding dementia cases occurring in the first 5 years to minimize the influence of reverse causation as suggested by previous studies. [20][21][22] Fourth, we re-modeled with missing data deleted. Finally, we remodeled by excluding participants with a history of stroke.…”

“…Second, we reanalyzed each index with AD and VD. Third, we re‐modeled by excluding dementia cases occurring in the first 5 years to minimize the influence of reverse causation as suggested by previous studies 20–22 . Fourth, we re‐modeled with missing data deleted.…”