Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis

Wu, Minghua; Li, Min; Yuan, Jun; Liang, Shuli; Chen, Zhaoyao; Ye, Min; Ryan, Paul M.; Clark, Cain C. T.; Tan, Shing Cheng; Rahmani, Jamal; Varkaneh, Hamed Kord; Bhagavathula, Akshaya Srikanth

doi:10.1016/j.phrs.2020.104693

Cited by 41 publications

(42 citation statements)

References 64 publications

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“…Other work suggests that HRT does not prevent cognitive decline (Henderson et al, 2016) and that long-term HRT may slightly increase risk for dementia (Savolainen-Peltonen et al, 2019;Wu et al, 2020). Indeed, a randomized, double-blinded placebo controlled trial of HRT (specifically, conjugated equine estrogens) in 95 recently postmenopausal women (ages 42-56) showed decreases in whole brain volume, increased ventricle expansion, and increased white matter hyperintensity volume over 48 months of HRT compared to the placebo group.…”

Section: Exogenous Sources Of Estrogen and Progesteronementioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen

Tubi

Bright

et al. 2021

Human Brain Mapping

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Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population-based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex-specific phenotypes in major brain diseases.

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Section: Exogenous Sources Of Estrogen and Progesteronementioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen

Tubi

Bright

et al. 2021

Human Brain Mapping

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“…85 A recent meta-analysis supported an association between hormone replacement therapy and AD with all-cause dementia. 86 In PSP, only one study from the ENGENE-PSP study investigated an association between lifetime estrogen exposure and PSP, suggesting a potential protective role of estrogen replacement therapy in PSP (OR = 0.52; 95% CI = 0.30-0.92; p = 0.03). 87 Further studies are needed to determine the effects of sex hormones, specifically exogenous estrogen, in PSP.…”

Section: Drugsmentioning

confidence: 99%

Environmental Risk Factors for Progressive Supranuclear Palsy

Park¹,

Ilango²,

Litvan³

2021

JMD

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Typically, progressive supranuclear palsy (PSP) is clinically characterized by slow vertical saccades or supranuclear gaze palsy, levodopa-resistant parkinsonism with predominant axial symptoms, and cognitive executive impairment. Over the past decades, various PSP phenotypes, including PSP with predominant parkinsonism, PSP with corticobasal syndrome, PSP with progressive gait freezing, and PSP with predominant frontal dysfunction, have been identified from pathologically confirmed cases. Expanding knowledge led to new diagnostic criteria for PSP that with increased disease awareness led to increased PSP prevalence estimates. The identification of environmental and modifiable risk factors creates an opportunity to intervene and delay the onset of PSP or slow disease progression. To date, despite the increasing number of publications assessing risk factors for PSP, few articles have focused on environmental and lifestyle risk factors for this disorder. In this article, we reviewed the literature investigating the relationship between PSP and several environmental and other modifiable lifestyle risk factors. In our review, we found that exposures to toxins related to diet, metals, well water, and hypertension were associated with increased PSP risk. In contrast, higher education and statins may be protective. Further case-control studies are encouraged to determine the exact role of these factors in the etiopathogenesis of PSP, which in turn would inform strategies to prevent and reduce the burden of PSP.

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“…Due to the small number of participants on HRT, we were unable to examine any potential effects of medication. Future studies with a larger number of participants on HRT could examine the role of either testosterone or estrogen therapies on relationships between brain integrity and metabolic function using a similar statistical technique to our analysis as research studies on HRT to protect against neurocognitive decline have shown mixed findings (LeBlanc et al, 2001;Wu et al, 2020). Somewhat challenging to interpret is the high level of betweenness of systolic blood pressure for females.…”

Section: Potential Mechanismsmentioning

confidence: 99%

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

Foret

Dekhtyar

Cole

et al. 2021

Front. Aging Neurosci.

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Hypothesis-driven studies have demonstrated that sex moderates many of the relationships between brain health and cardiometabolic disease, which impacts risk for later-life cognitive decline. In the present study, we sought to further our understanding of the associations between multiple markers of brain integrity and cardiovascular risk in a midlife sample of 266 individuals by using network analysis, a technique specifically designed to examine complex associations among multiple systems at once. Separate network models were constructed for male and female participants to investigate sex differences in the biomarkers of interest, selected based on evidence linking them with risk for late-life cognitive decline: all components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia); neuroimaging-derived brain-predicted age minus chronological age; ratio of white matter hyperintensities to whole brain volume; seed-based resting state functional connectivity in the Default Mode Network, and ratios of N-acetyl aspartate, glutamate and myo-inositol to creatine, measured through proton magnetic resonance spectroscopy. Males had a sparse network (87.2% edges = 0) relative to females (69.2% edges = 0), indicating fewer relationships between measures of cardiometabolic risk and brain integrity. The edges in the female network provide meaningful information about potential mechanisms between brain integrity and cardiometabolic health. Additionally, Apolipoprotein ϵ4 (ApoE ϵ4) status and waist circumference emerged as central nodes in the female model. Our study demonstrates that network analysis is a promising technique for examining relationships between risk factors for cognitive decline in a midlife population and that investigating sex differences may help optimize risk prediction and tailor individualized treatments in the future.

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Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis

Cited by 41 publications

References 64 publications

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Environmental Risk Factors for Progressive Supranuclear Palsy

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

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