Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study

Shang, Xianwen; Hill, Edward; Zhu, Zhuoting; Kiburg, Katerina; Wang, Wei; Huang, Yu; Zhang, Xueli; Tang, Shulin; Hu, Yijun; Ge, Zongyuan; Yu, Honghua; He, Mingguang

doi:10.1186/s13195-022-01140-2

Cited by 8 publications

(3 citation statements)

References 47 publications

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“…1.198). In another study of UK Biobank data, men had a higher risk of all-cause, young-onset and late-onset dementias than women [13].…”

Section: Resultsmentioning

confidence: 95%

RPTOR is an Alzheimer’s Disease susceptibility gene associated with Alzheimer’s Disease risk factors BMI and infectious encephalitis

Lehrer,

Rheinstein

2023

Preprint

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Background: In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer's disease (AD) that was 31 times higher. In a previous study, we were able to confirm the association of viral encephalitis with AD and suggest that West Nile Virus infection is a significant AD risk factor. A genome wide association study (GWAS) with UK Biobank data revealed that the gene RAR Related Orphan Receptor B (RORB), previously linked to AD, is significantly associated with viral encephalitis. Methods: In the current study we used data from PheWeb to identify genes other than RORB that might be involved in both infectious encephalitis and AD. We used UK Biobank data to examine gene expression and phenotypic expression. Results: PheWeb identified additional genes associated with both infectious encephalitis and AD. RPTOR, a gene associated with the mTOR pathway, emerges as significant. Analyses of UK Biobank data reveal the impact of RPTOR on AD risk, with carriers of the minor allele A exhibiting decreased prevalence in subjects under age 55. Further analysis demonstrates that RPTOR genotypes influence Body Mass Index (BMI) in subjects of all ages, with carriers of the minor allele A having lower BMI. Logistic regression analyses confirm the association between reduced BMI and increased AD risk, along with the established factor of age. Conclusion: RPTOR may represent an early onset AD gene, though mTOR's role in AD and BMI is complex. Nevertheless, RPTOR and mTOR could represent potential therapeutic targets for AD.

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“…1.198). In another study of UK Biobank data, men had a higher risk of all-cause, young-onset and late-onset dementias than women [13].…”

Section: Resultsmentioning

confidence: 95%

RPTOR is an Alzheimer’s Disease susceptibility gene associated with Alzheimer’s Disease risk factors BMI and infectious encephalitis

Lehrer,

Rheinstein

2023

Preprint

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“…Most studies report that AD is more common in women; however, in the UKBB, AD is more common in men, which has been reported previously. In another study of UK Biobank data, men had a higher risk of all-cause, young-onset and late-onset dementias than women [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

RPTOR Is an Alzheimer’s Disease Susceptibility Gene Associated with the Risk Factors Body Mass Index and Infectious Encephalitis

Lehrer,

Rheinstein

2024

Journal of Alzheimer's Disease Reports

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Background: In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer’s disease (AD) that was 31 times higher. In a previous study, we were able to confirm the association of viral encephalitis with AD and suggest that West Nile Virus infection is a significant AD risk factor. A genome wide association study (GWAS) with UK Biobank data revealed that the gene RAR Related Orphan Receptor B (RORB) is significantly associated with viral encephalitis. Objective: To use data from the 8 PheWeb datasets to try to identify genes other than RORB that might be involved in both infectious encephalitis and AD. Methods: PheWeb includes data from UKBB and 5 other databanks. We used UK Biobank data to examine gene expression and phenotypic expression. Results: PheWeb identified additional genes associated with both infectious encephalitis and AD. RPTOR, a gene associated with the mTOR pathway, emerges as significant. Analyses of UK Biobank data reveal the impact of RPTOR on AD risk, with carriers of the minor allele A exhibiting decreased prevalence in subjects under age 55. Further analysis demonstrates that RPTOR genotypes influence body mass index (BMI) in subjects of all ages, with carriers of the minor allele A having lower BMI. Logistic regression analyses confirm the association between reduced BMI and increased AD risk, along with the established factor of age. Conclusions: RPTOR may represent an AD gene, though mTOR’s role in AD and BMI is complex. Nevertheless, RPTOR and mTOR could represent potential therapeutic targets for AD.

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“…In the UK Biobank study (N =5,117,381), 452 were noted to have young-onset dementia and 5476 to have late-onset dementia [28]. Health-related conditions explained 74% of the variance and was a stronger mediator for late-onset dementia.…”

Section: Negative Physical Predictorsmentioning

confidence: 99%

Dementia Disorders: A Narrative Review

Field

2024

J Clin Psychol Neurol

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This narrative review of research includes summaries of 40 papers on dementia disorders that were published during 2023. The publications of this period are primarily randomized controlled trials and systematic reviews/ meta-analyses of randomized controlled trials. A few of these are focused on the prevalence of dementia which approximated one per cent of the world’s population. Only a few studies focused on effects of dementia disorders including memory loss, discrimination, pain, depression and suicidality. Most of the studies addressed predictors of dementia disorders including neurotic personality, frequent tv/computer use and excessive exposure to metals. Loss of short-term memory and other negative experiences including negative life events, loneliness, stress and depression were also significant predictor variables in this recent literature. Physical conditions that were predictive of dementia included pain, hypertension, atrial fibrillation, multi-morbidities, inflammation, encephalitis and neuropathology. Potential underlying mechanisms included dysfunctional neurotransmitter systems (serotonergic, noradrenergic and dopaminergic) and gray matter loss in prefrontal, temporal and other regions associated with memory. Several research groups reported on effective interventions including a Mediterranean diet, plant-based diets, medicinal plants, psychedelics, second generation antidepressants, blood pressure medication, music therapy, aromatherapy and other alternative therapies. Methodological problems relate to the variability in the assessments of dementia disorders, the self-report measures and the cross-sectional data that are not definitive about directionality of predictors and effects of dementia disorders.

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Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study

Cited by 8 publications

References 47 publications

RPTOR is an Alzheimer’s Disease susceptibility gene associated with Alzheimer’s Disease risk factors BMI and infectious encephalitis

RPTOR is an Alzheimer’s Disease susceptibility gene associated with Alzheimer’s Disease risk factors BMI and infectious encephalitis

RPTOR Is an Alzheimer’s Disease Susceptibility Gene Associated with the Risk Factors Body Mass Index and Infectious Encephalitis

Dementia Disorders: A Narrative Review

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