Evaluation of Selective Survival and Sex/Gender Differences in Dementia Incidence Using a Simulation Model

Shaw, Crystal; Hayes‐Larson, Eleanor; Glymour, M. Maria; Dufouil, Carole; Hohman, Timothy J.; Whitmer, Rachel A.; Kobayashi, Lindsay C.; Brookmeyer, Ron; Mayeda, Elizabeth Rose

doi:10.1001/jamanetworkopen.2021.1001

Cited by 29 publications

(35 citation statements)

References 44 publications

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“…264 Recent studies have supported the notion that selection bias contributes to reports of sex and gender differences in Alzheimer's dementia. 273 More research is needed to support this interpretation.…”

Section: Differences Between Women and Men In The Prevalence And Risk...mentioning

confidence: 99%

“…278,279 Other societal gender differences may also be at play, such as differences in occupational attainment between men and women, with a recent study showing that women who participated in the paid workforce earlier in life had better cognitive outcomes after age 60. [280][281][282] It is unclear whether genetic risk operates differently in women and men in the development of, or susceptibility to, Alzheimer's pathology. 283 A number of studies have shown that the APOE-e4 genotype, the best known common genetic risk factor for Alzheimer's dementia, may have a stronger association with Alzheimer's dementia 284,285 and neurodegeneration 286 in women than in men.…”

Section: Differences Between Women and Men In The Prevalence And Risk...mentioning

confidence: 99%

“…A study using Framingham Heart Study data suggested that men in the study appear to have a lower risk for dementia due to “survival bias,” in which the men who survived to age 65 or beyond and were included in the study were the ones with a healthier cardiovascular risk profile (men have a higher rate of death from cardiovascular disease in middle age than women) and thus a lower risk for dementia 264 . Recent studies have supported the notion that selection bias contributes to reports of sex and gender differences in Alzheimer's dementia 273 . More research is needed to support this interpretation.…”

Section: Prevalencementioning

confidence: 99%

“…Interestingly, European studies have found that the relationship of lower education with dementia outcomes may be stronger in women than men 278,279 . Other societal gender differences may also be at play, such as differences in occupational attainment between men and women, with a recent study showing that women who participated in the paid workforce earlier in life had better cognitive outcomes after age 60 280–282 …”

Section: Prevalencementioning

confidence: 99%

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2022 Alzheimer's disease facts and figures

2022

Alzheimer's & Dementia

1,559

664

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This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. The Special Report discusses consumers' and primary care physicians' perspectives on awareness, diagnosis and treatment of mild cognitive impairment (MCI), including MCI due to Alzheimer's disease. An estimated 6.5 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available. Alzheimer's disease was officially listed as the sixth-leading cause of death in the United States in 2019 and the seventh-leading cause of death in 2020 and 2021, when COVID-19 entered the ranks of the top ten causes of death. Alzheimer's remains the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. More than 11 million family members and other unpaid caregivers provided an estimated 16 billion hours of care to people with Alzheimer's or other dementias in 2021. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $271.6 billion in 2021. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes -costs that have been aggravated by COVID-19. Members of the dementia care workforce have also been affected by COVID-19. As essential care workers, some have opted to change jobs to protect their own health and the health of their families. However, this occurs at a time when more members of the dementia care workforce are needed. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are almost three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 22 times as great. Total payments in 2022 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $321 billion. A recent survey commissioned by the Alzheimer's Association revealed several barriers to consumers' understanding of MCI. The survey showed low awareness of MCI among Americans, a reluctance among Americans to see their doctor after noticing MCI symptoms, and persistent challenges for primary care physicians in diagnosing MCI. Survey results indicate the need to improve MCI 700

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Section: Differences Between Women and Men In The Prevalence And Risk...mentioning

confidence: 99%

Section: Differences Between Women and Men In The Prevalence And Risk...mentioning

confidence: 99%

Section: Prevalencementioning

confidence: 99%

Section: Prevalencementioning

confidence: 99%

See 2 more Smart Citations

2022 Alzheimer's disease facts and figures

2022

Alzheimer's & Dementia

1,559

664

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“…The UK dementia report states that more females have AD and that this trend is likely to remain with a F:M ratio of approximately 2 to 1 in the projected dementia incidence for 2051 [ 13 ]. Although it has been recently reported that selective survival may contribute to sex/gender differences in dementia incidence, this does not preclude the additional contributions from biological mechanisms [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort

Xu¹,

Green²,

Kim³

et al. 2021

Biomedicines

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Background: physiological differences between males and females could contribute to the development of Alzheimer’s Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites’ discriminatory performance in AD. Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046). Conclusions: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.

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