A Lifecourse Perspective on Female Sex-Specific Risk Factors for Later Life Cognition

Peterson, Amalia; Tom, Sarah E.

doi:10.1007/s11910-021-01133-y

Cited by 20 publications

(19 citation statements)

References 105 publications

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“…Top 30 features for the plasma and brain models intersect on 5-aminovaleric acid, methylhistidine metabolism, serotonin, trans-4-hydroxyproline, and on involvement of acylcarnitines, triglycerides, lysophosphatidylcholines, and cholesteryl esters. The models tend to better classify females in both tissue cohorts and given the incidence of AD is higher among females [ 34 ], this increase seems to be reflected in metabolism, although further study is needed to confirm this trend.…”

Section: Discussionmentioning

confidence: 99%

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Kalecky

German

Montillo

2022

JAD

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Background: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer’s disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. Objective: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. Methods: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer’s Research and Care Consortium – TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). Results: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75–88%); for females specifically, AUC = 88% (CI95 = 80–95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71–85%); for females AUC = 84% (CI95 = 74–92%). Conclusion: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.

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Section: Discussionmentioning

confidence: 99%

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Kalecky

German

Montillo

2022

JAD

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“…For instance, pregnancy events leave “residual signatures” on inflammatory markers, blood counts, and telomere length that could in turn influence immunologic and inflammatory trajectories over the life course, thereby altering the risk for dementia ( Cramer and Vitonis, 2017 ; Pollack et al, 2018 ). Pregnancy might also have an impact on women’s brain aging trajectories through modifying estrogen levels that may have direct and indirect effects on neurotransmitters, modulate neuronal structures, enhance synaptic plasticity, increase cerebral blood flow, and increase breakdown of β-amyloid precursors ( Genazzani et al, 2007 ; Naftolin et al, 2018 ; Peterson and Tom, 2021 ). It may also be attributable to various pregnancy-associated factors such as health, employment, and lifestyle during or after pregnancy ( Jang et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Associations of Parity With Change in Global Cognition and Incident Cognitive Impairment in Older Women

Zhou

Liu

Zou³

et al. 2022

Front. Aging Neurosci.

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BackgroundThe evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia.MethodsUsing the Women’s Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996–2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996–2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups.ResultsOver an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1–3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56–0.99) and 0.71 (0.53–0.96), respectively (P < 0.01). Similarly, a parity of 1–3 and ≥4 was related to slower cognitive decline (β = 0.164, 0.292, respectively, P < 0.05).ConclusionHigher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women.

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“…Given that estradiol and progesterone may enhance memory retention by altering synaptic plasticity in brain regions critical to memory processes (i.e., hippocampus and prefrontal cortex) (Foy et al, 2010 ; Frankfurt and Luine, 2015 ), sex differences may be driven by female sex hormones (Morse et al, 1986 ; Sandstrom and Williams, 2001 ). As we discuss in further detail below, fluctuations in estrogens and progesterone levels during the menstrual cycle, pregnancy, and menopause may result in changes in memory performance across the adult female lifespan and may account, in part, for the observed sex differences in ADRD prevalence in later life (Peterson and Tom, 2021 ).…”

Section: Sex Differences In Sleep Memory and Neural Plasticitymentioning

confidence: 99%

Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan

Harrington

Parisi

Duan

et al. 2022

Front. Aging Neurosci.

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As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer’s disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.

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A Lifecourse Perspective on Female Sex-Specific Risk Factors for Later Life Cognition

Cited by 20 publications

References 105 publications

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Associations of Parity With Change in Global Cognition and Incident Cognitive Impairment in Older Women

Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan

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