Association of sex differences in dementia risk factors with sex differences in memory decline in a population-based cohort spanning 20–76 years

Anstey, Kaarin J.; Peters, Ruth; Mortby, Moyra E.; Kiely, Kim M.; Eramudugolla, Ranmalee; Cherbuin, Nicolas; Huque, Hamidul; Dixon, Roger A.

doi:10.1038/s41598-021-86397-7

Cited by 62 publications

(59 citation statements)

References 39 publications

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“…The elimination of the female memory advantage is particularly striking as larger episodic memory decline than average is a sign of Alzheimer's disease (12,13), and women are more likely than men to have Alzheimer's disease (1, 2, 3). The higher rates of Alzheimer's disease in women were previously contradicted by the finding of less episodic memory decline in women than men (6,7,8,9,10,11,27). We speculate that accounting for modifiable risk factors clarifies this contradiction.…”

Section: Discussionmentioning

confidence: 99%

“…In women, hypertension (6) and low education (20) are associated with greater episodic memory decline, and hypertension increases the likelihood of mild cognitive impairment (MCI; 21) and dementia (22,23,24). Diabetes is associated with greater cognitive impairment in women (25), and smoking is associated with greater episodic memory decline in men (6,26,27), but both factors have no sex-specific effects on general cognitive decline or dementia likelihood (24, 28). Depression is associated with greater cognitive decline and dementia in women on some studies (29,30), and on men in others (6,21).…”

Section: Some Individual Modifiable Risk Factors Differentially Influence Cognitive Decline and Riskmentioning

confidence: 99%

“…Diabetes is associated with greater cognitive impairment in women (25), and smoking is associated with greater episodic memory decline in men (6,26,27), but both factors have no sex-specific effects on general cognitive decline or dementia likelihood (24, 28). Depression is associated with greater cognitive decline and dementia in women on some studies (29,30), and on men in others (6,21).…”

Section: Some Individual Modifiable Risk Factors Differentially Influence Cognitive Decline and Riskmentioning

confidence: 99%

“…Recent calls highlight the need to study sex differences in dementia risk, based on findings that women are more likely than men to develop Alzheimer's disease (1,2,3), although these differences vary across populations (4,5). The higher prevalence of Alzheimer's disease in women is contradicted by findings of better memory for events (episodic memory) in women compared to men (6,7) and less age-related memory decline (6,7,8,9,10,11), despite greater episodic memory impairment than normal being a potential precursor to Alzheimer's disease and a defining feature of Alzheimer's disease (12,13). By contrast, no consistent sex differences occur in cognitive decline of other abilities impacted by Alzheimer's disease (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Sex differences and Modifiable Dementia Risk Factors Synergistically Influence Memory over the Adult Lifespan

LaPlume¹,

McKetton²,

Levine³

et al. 2021

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INTRODUCTION: More women than men develop Alzheimer’s disease, yet women show less age-related episodic memory decline, a contradiction that may be accounted for by modifiable risk factors for dementia. METHODS: Associations between sex, modifiable dementia risk factors, and cognition were measured in a cross-sectional online sample (n = 21,840, ages 18-89). RESULTS: Across four tests of associative memory and executive functions, only a Face-Name Association task revealed sex differences in age-related decline. Men had worse associative memory than women (the equivalent of four years of aging). Each additional risk factor had the equivalent of three and a half years of aging. Men had greater age-related decline in associative memory than women among those with no to one risk factors, but multiple risk factors eliminated the female advantage. DISCUSSION: Because the relationship between dementia risk factors and age-related memory decline differs for men and women, sex-specific dementia prevention approaches are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Some Individual Modifiable Risk Factors Differentially Influence Cognitive Decline and Riskmentioning

confidence: 99%

Section: Some Individual Modifiable Risk Factors Differentially Influence Cognitive Decline and Riskmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sex differences and Modifiable Dementia Risk Factors Synergistically Influence Memory over the Adult Lifespan

LaPlume¹,

McKetton²,

Levine³

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Sex differences have been observed in the prevalence and manifestation of a number of neurological and psychiatric diseases (Irvine et al, 2012, Eid et al, 2019). Females are more likely to be diagnosed with multiple sclerosis, major depressive disorder, and have a greater lifetime risk of Alzheimer’s Disease compared to males, whereas males are more likely to be diagnosed with autism spectrum disorder, attention and hyperactivity disorder, and Parkinson’s Disease (Gillies et al 2014; Mauvais-Jarvis et al, 2020; Gutiérrez-Lobos et al, 2002; Liu et al, 2019; Anstey et al, 2021; Nebel et al, 2018). Even in diseases that do not show strong sex differences in prevalence, age of disease onset or manifestation can be different between the sexes (Häfner et al, 1992; Liu and Mager, 2016).…”

Section: Introductionmentioning

confidence: 99%

Harnessing the Power of Sex Differences: What a Difference Ten Years Did Not Make

et al. 2021

Preprint

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Sex differences exist in a variety of neurological and psychiatric diseases in terms of prevalence, manifestation, and treatment but most past research has been conducted in males. Multiple mandates have been initiated across funding agencies (National Institute of Health, Horizon Europe, Canadian Institute for Health Research) and scientific publishers (Sex and Gender Equity in Research) for biomedical and clinical research to include both males and females in research and reporting. Although more studies are including males and females in their research there are issues in how studies are incorporating males and females in their experiments, as about a third of studies that use males and females do not report sample size and only half are conducting any analysis by sex. Furthermore, what has been lacking in the literature is a detailed assessment of not only how sex is reported in papers (e.g. sample sizes disclosed, balanced design, sex used consistently throughout the experiments) but also how the variable sex is included in any analyses (e.g. covariate). Here we investigated all papers in 2009 and 2019 in three high ranking journals for each of Neuroscience and Psychiatry. We found that there was a 30% increase in the percentage of papers that included both sexes from 2009 to 2019 such that 68% of studies in Neuroscience and Psychiatry used both males and females in 2019. Despite this increase, in 2019 only 19% of all studies used an optimal design for discovery of possible sex differences and only 5% analyzed with sex as a discovery variable. Of the studies that used males and females - 25% of studies do not disclose sample sizes, 36% of studies used an unbalanced design, and 15% of studies did not use both sexes consistently throughout the paper. The percentage of single sex papers remains unchanged across the ten years at 3% for female-only studies compared to 27% for male-only studies across both disciplines. Neuroscience had fewer papers that analyzed by sex at 20% compared to 61% of Psychiatry papers. We hope that these data will make it evident that more needs to be done to improve the inclusion of males and females in future studies to improve the health of men and women.

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Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers

et al. 2023

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ImportanceThe association between hypertension developed before midlife and late-life brain health is understudied and, because of the cardioprotective benefits of estrogen before menopause, may differ by sex.ObjectiveTo assess the association of early adulthood hypertension and blood pressure (BP) change with late-life neuroimaging biomarkers and examine potential sex differences.Design, Setting, and ParticipantsThis cohort study used data from the Study of Healthy Aging in African Americans (STAR) and Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, which were harmonized longitudinal cohorts of racially and ethnically diverse adults aged 50 years and older from the San Francisco Bay area and Sacramento Valley in California. The STAR was conducted from November 6, 2017, to November 5, 2021, and the KHANDLE study was conducted from April 27, 2017, to June 15, 2021. The current study included 427 participants from the KHANDLE and STAR studies who received health assessments between June 1, 1964, and March 31, 1985. Regional brain volumes and white matter (WM) integrity were measured via magnetic resonance imaging between June 1, 2017, and March 1, 2022.ExposuresHypertension status (normotension, transition to hypertension, and hypertension) and BP change (last measure minus first measure) were assessed at 2 multiphasic health checkups (MHCs; 1964-1985) in early adulthood (ages 30-40 years).Main Outcomes and MeasuresRegional brain volumes and WM integrity were measured using 3T magnetic resonance imaging and z standardized. General linear models adjusted for potential confounders (demographic characteristics and study [KHANDLE or STAR]) were used to assess the association of hypertension and BP change with neuroimaging biomarkers. Sex interactions were tested.ResultsAmong 427 participants, median (SD) ages were 28.9 (7.3) years at the first MHC, 40.3 (9.4) years at the last MHC, and 74.8 (8.0) years at neuroimaging. A total of 263 participants (61.6%) were female and 231 (54.1%) were Black. Overall, 191 participants (44.7%) had normotension, 68 (15.9%) transitioned to hypertension, and 168 (39.3%) had hypertension. Compared with participants who had normotension, those who had hypertension and those who transitioned to hypertension had smaller cerebral volumes (hypertension: β = −0.26 [95% CI, −0.41 to −0.10]; transition to hypertension: β = −0.23 [95% CI, −0.44 to −0.23]), with similar differences in cerebral gray matter volume (hypertension: β = −0.32 [95% CI, −0.52 to −0.13]; transition to hypertension: β = −0.30 [95% CI, −0.56 to −0.05]), frontal cortex volume (hypertension: β = −0.43 [95% CI, −0.63 to −0.23]; transition to hypertension: β = −0.27 [95% CI, −0.53 to 0]), and parietal cortex volume (hypertension: β = −0.22 [95% CI, −0.42 to −0.02]; transition to hypertension: β = −0.29 [95% CI, −0.56 to −0.02]). Participants with hypertension also had smaller hippocampal volume (β = −0.22; 95% CI, −0.42 to −0.02), greater ventricular volumes (lateral ventricle: β = 0.44 [95% CI, 0.25-0.63]; third ventricle: β = 0.20 [95% CI, 0.01-0.39]), larger free water volume (β = 0.35; 95% CI, 0.18-0.52), and lower fractional anisotropy (β = −0.26; 95% CI, −0.45 to −0.08) than those who had normotension. Holding hypertension status constant, a 5-mm Hg increase in systolic BP was associated with smaller temporal cortex volume (β = −0.03; 95% CI, −0.06 to −0.01), while a 5-mm Hg increase in diastolic BP was associated with smaller parietal cortex volume (β = −0.06; 95% CI, −0.10 to −0.02). The negative association of hypertension and BP change with regional brain volumes appeared stronger in men than women for some regions.Conclusions and RelevanceIn this cohort study, early adulthood hypertension and BP change were associated with late-life volumetric and WM differences implicated in neurodegeneration and dementia. Sex differences were observed for some brain regions whereby hypertension and increasing BP appeared more detrimental for men. These findings suggest that prevention and treatment of hypertension in early adulthood is important for late-life brain health, particularly among men.

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Association of sex differences in dementia risk factors with sex differences in memory decline in a population-based cohort spanning 20–76 years

Cited by 62 publications

References 39 publications

Sex differences and Modifiable Dementia Risk Factors Synergistically Influence Memory over the Adult Lifespan

Sex differences and Modifiable Dementia Risk Factors Synergistically Influence Memory over the Adult Lifespan

Harnessing the Power of Sex Differences: What a Difference Ten Years Did Not Make

Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers

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