Adiponectin, Leptin, and Resistin and the Risk of Dementia

Abstract

Background Adipokines are hormones secreted by adipose tissue with roles in energy homeostasis and regulation of metabolism. Their dysregulation is suggested to contribute to the increased risk of dementia seen with midlife obesity, but longitudinal studies investigating this are scarce. We determined the association between plasma levels of adiponectin, leptin and resistin with the risk of dementia. Methods We performed a case-cohort study embedded in the prospective, population-based Rotterdam Study. Plasma levels of the adiponectin, leptin and resistin were measured at baseline (1997-1999) in a random sub-cohort of 945 participants without dementia, and additionally in 177 participants, who were diagnosed with dementia during follow-up (until January 1, 2018). Results Higher levels of leptin and resistin were associated with a decreased risk of dementia (adjusted hazard ratio [95% confidence interval] per SD increase of log transformed values: 0.85 [0.72-1.00] for leptin; 0.82 [0.71-0.95] for resistin). The association of leptin with dementia was further modified by body mass index and by APOE ε4 carrier status. Adiponectin levels were not associated with the risk of dementia. Conclusions These findings support the hypothesis that adipokines have a role in the pathophysiology of dementia. Future studies are warranted to confirm the findings and to explore the underlying mechanisms.

Bidirectional communication between brain and visceral white adipose tissue: Its potential impact on Alzheimer's disease

“…Many of these hormones have been proved to participate in the pathogenesis of AD ( Table 1 ), including metabolism of Aβ, 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 phosphorylation of tau, 182 , 183 , 189 , 191 , 192 hippocampal neurogenesis, 181 , 193 , 194 neurodegeneration, 181 , 195 synaptic function, 196 , 197 , 198 , 199 , 200 neuroinflammation 186 , 201 , 202 , 203 , 204 , 205 , 206 and oxidative stress. 181 , 182 , 184 , 206 , 207 , 208 All the findings indicate the vWAT-derived hormones could be a mediator between vWAT and AD. Nevertheless, to our knowledge, the direct research evidence on whether vWAT is involved in the pathogenesis of AD is still lacking so far.…”

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

“…High levels of leptin are seen in persons with adiposity, while their levels drop with weight loss. As such, decreased leptin levels in older adults due to weight loss may contribute to their increased risk of dementia 42 . Estrogen levels may further explain protective effects of adiposity among older women 16 .…”

“…As such, decreased leptin levels in older adults due to weight loss may contribute to their increased risk of dementia. 42 Estrogen levels may further explain protective effects of adiposity among older women. 16 In fact, in postmenopausal women, adipose tissue is the primary source F I G U R E 1 Subgroup and sensitivity analyses for adiposity at baseline in association with the risk of dementia.…”

Circulating adiponectin levels, expression of adiponectin receptors, and methylation of adiponectin gene promoter in relation to Alzheimer’s disease

“…As mentioned, the association between adiponectin and AD is disputed; where some studies suggest that lower levels of circulating adiponectin have a neuroprotective role [17], while some studies report an increased risk of AD [40]. Furthermore, one recent prospective population-based cohort study revealed no relationship between serum adiponectin levels and the risk of dementia [41]. In our study, we have observed an elevated level of adiponectin in the blood serum of AD subjects compared to control, in line with the studies in which higher serum adiponectin levels were significantly associated with cognitive deficiency [42], MCI, and AD [12,14,40,43,44].…”