Sex‐specific effects of high‐fat diet on cognitive impairment in a mouse model of VCID

Mid‐life metabolic disease (ie, obesity, diabetes, and prediabetes) causes vascular dysfunction and is a risk factor for vascular contributions to cognitive impairment and dementia (VCID), particularly in women. Using middle‐aged mice, we modeled metabolic disease (obesity/prediabetes) via chronic h...

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Bibliographic Details
Published in:The FASEB journal 2020-11, Vol.34 (11), p.15108-15122
Main Authors: Salinero, Abigail E., Robison, Lisa S., Gannon, Olivia J., Riccio, David, Mansour, Febronia, Abi‐Ghanem, Charly, Zuloaga, Kristen L.
Format: Article
Language:English
Subjects:
Animals
cerebral blood flow
Cognitive Dysfunction - etiology
Cognitive Dysfunction - pathology
Dementia, Vascular - complications
Diet, High-Fat - adverse effects
diet‐induced obesity
Disease Models, Animal
Female
Male
Maze Learning
Mice
Mice, Inbred C57BL
prediabetes
sex
Sex Factors
Spatial Memory
vascular contributions to cognitive impairment and dementia
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Summary:Mid‐life metabolic disease (ie, obesity, diabetes, and prediabetes) causes vascular dysfunction and is a risk factor for vascular contributions to cognitive impairment and dementia (VCID), particularly in women. Using middle‐aged mice, we modeled metabolic disease (obesity/prediabetes) via chronic high‐fat (HF) diet and modeled VCID via unilateral common carotid artery occlusion. VCID impaired spatial memory in both sexes, but episodic‐like memory in females only. HF diet caused greater weight gain and glucose intolerance in middle‐aged females than males. HF diet alone impaired episodic‐like memory in both sexes, but spatial memory in females only. Finally, the combination of HF diet and VCID elicited cognitive impairments in all tests, in both sexes. Sex‐specific correlations were found between metabolic outcomes and memory. Notably, both visceral fat and the pro‐inflammatory cytokine tumor necrosis factor alpha correlated with spatial memory deficits in middle‐aged females, but not males. Overall, our data show that HF diet causes greater metabolic impairment and a wider array of cognitive deficits in middle‐aged females than males. The combination of HF diet with VCID elicits deficits across multiple cognitive domains in both sexes. Our data are in line with clinical data, which shows that mid‐life metabolic disease increases VCID risk, particularly in females.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202000085R