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

Salinero, Abigail E.; Robison, Lisa S.; Gannon, Olivia J.; Riccio, David; Mansour, Febronia; Abi‐Ghanem, Charly; Zuloaga, Kristen L.

doi:10.1096/fj.202000085r

Cited by 30 publications

(47 citation statements)

References 68 publications

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“…We found that unilateral carotid artery occlusion surgery (MxD mice) caused deficits in cerebral blood flow in the cortical surface that persisted 4 months after surgery. This is in line with our previous work, and that of others, documenting prolonged deficits in blood flow in the ipsilateral hemisphere (19,(42)(43)(44)58). While we observed the expected effect of MxD to cause hypoperfusion, we did not observe any sex or diet differences.…”

Section: Neuropathology Findingssupporting

confidence: 93%

“…For example, we have shown that HF diet impairs adult hippocampal neurogenesis in female, but not male mice (18). Further, we recently found that HF diet in middle aged mice causes a wider array of cognitive deficits in females compared to males (19). Others have found that a HF diet in the 3xTg-AD model of AD exacerbates cognitive impairment (20)(21)(22)(23)(24)(25) and AD pathology such as brain atrophy (20), inflammation (22,26), and Aβ load (26)(27)(28).…”

Section: Introductionmentioning

confidence: 94%

“…Cerebral Blood Flow Measurement: Cerebral blood flow was measured via laser speckle contrast imaging (moor FLPI full field laser perfusion imager; Moor Instruments, Wilmington, DE, USA) under isoflurane anesthesia as previously described (19). Image acquisition (5-minute scan), processing, and analysis were performed using moorFLPI Review V4.0 software (Moor Instruments, Wilmington, DE, USA).…”

Section: Surgical Model Of Mxdmentioning

confidence: 99%

“…Glucose Tolerance Test: As previously described (19,29,31), mice were given a glucose tolerance test (GTT) to assess diabetic status after being on either the control or HF diet for 3 months. The mice were fasted overnight, and their fasting blood glucose levels were measured (t=0) using a glucometer (Verio IQ, OneTouch, Sunnyvale CA, USA) from their tail vein.…”

Section: Surgical Model Of Mxdmentioning

confidence: 99%

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High fat diet exacerbates cognitive decline in mouse models of Alzheimer’s disease and mixed dementia in a sex-dependent manner

Gannon

Robison

Salinero

et al. 2021

Preprint

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Approximately 70% of Alzheimer's disease (AD) patients have co-morbid vascular contributions to cognitive impairment and dementia (VCID); this highly prevalent overlap of dementia subtypes is known as mixed dementia (MxD). AD is more prevalent in women, while VCID is slightly more prevalent in men. Sex differences in risk factors may contribute to sex differences in dementia subtypes. Unlike metabolically healthy women, diabetic women are more likely to develop VCID than diabetic men. Prediabetes is 3x more prevalent than diabetes and is linked to earlier onset of dementia in women, but not men. How prediabetes influences underlying pathology and cognitive outcomes across different dementia subtypes is unknown. To fill this gap in knowledge, we investigated the impact of diet-induced prediabetes and biological sex on cognitive function and neuropathology in mouse models of AD and MxD. Male and female 3xTg-AD mice received a sham (AD model) or unilateral common carotid artery occlusion surgery to induce chronic cerebral hypoperfusion (MxD model). Mice were fed a control or high fat (HF; 60% fat) diet for 3 months prior to behavior assessment. In both sexes, HF diet elicited a prediabetic phenotype (impaired glucose tolerance) and weight gain. In females, but not males, metabolic consequences of a HF diet were more severe in AD or MxD mice compared to WT. In both sexes, HF-fed AD or MxD mice displayed deficits in spatial memory in the Morris water maze (MWM). In females, but not males, HF-fed AD and MxD mice also displayed impaired spatial learning in the MWM. In females, but not males, AD or MxD caused deficits in activities of daily living, regardless of diet. Astrogliosis was more severe in AD and MxD females compared to males. Further, HF diet caused greater accumulation of amyloid beta in MxD females compared to MxD males. In females, but not males, more severe glucose intolerance (prediabetes) was correlated with increased hippocampal microgliosis. In conclusion, high fat diet had a wider array of metabolic, cognitive, and neuropathological consequences in AD and MxD females compared to males. These findings shed light on potential underlying mechanisms by which prediabetes may lead to earlier dementia onset in women.

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Section: Neuropathology Findingssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 94%

Section: Surgical Model Of Mxdmentioning

confidence: 99%

Section: Surgical Model Of Mxdmentioning

confidence: 99%

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High fat diet exacerbates cognitive decline in mouse models of Alzheimer’s disease and mixed dementia in a sex-dependent manner

Gannon

Robison

Salinero

et al. 2021

Preprint

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“…The effect of metabolic disease on VCID risk is even greater for women compared to men. In line with this clinical data, using mouse models of metabolic disease (chronic high fat diet) and VCID (chronic cerebral hypoperfusion), we have found that high-fat diet causes greater metabolic impairment and a wider array of cognitive deficits in middle-aged females compared to males [37]. We have found that metabolic disease severity is more strongly associated with white matter damage, astrogliosis [38], and reduced neurogenesis [39] in females compared to males.…”

Section: Kristen L Zuloagasupporting

confidence: 72%

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

et al. 2021

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White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [ 1 ] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting was held virtually on March 3–4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust–sponsored workshops (Barone et al. in J Transl Med 14:1–14, [ 2 ]; Sorond et al. in GeroScience 42:81–96, [ 3 ]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.

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Personalized nutrition for dementia prevention

Samieri

Yassine

Lent

et al. 2021

Alzheimer's & Dementia

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The role of nutrition has been investigated for decades under the assumption of onesize-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts.

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

Cited by 30 publications

References 68 publications

High fat diet exacerbates cognitive decline in mouse models of Alzheimer’s disease and mixed dementia in a sex-dependent manner

High fat diet exacerbates cognitive decline in mouse models of Alzheimer’s disease and mixed dementia in a sex-dependent manner

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

Personalized nutrition for dementia prevention

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