Sex differences in Alzheimer risk

Mosconi, Lisa; Berti, Valentina; Quinn, Crystal; McHugh, Pauline; Petrongolo, Gabriella; Varsavsky, Isabella; Osorio, Ricardo S.; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S.; Leon, Mony J. de; Brinton, Roberta Dı́az

doi:10.1212/wnl.0000000000004425

Cited by 221 publications

(194 citation statements)

References 43 publications

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“…These abnormalities included reduced CMRglc, increased Aβ accumulation, and gray and white matter loss in key brain regions for AD, such as parieto-temporal, posterior cingulate, and frontal cortices. Biomarker deficits were most pronounced in postmenopausal women, intermediate in perimenopausal women, and lowest in premenopausal women (9). …”

Section: Imaging the Menopausal Brainmentioning

confidence: 98%

“…Both postmenopausal and perimenopausal groups exhibited AD biomarker abnormalities as compared to age-matched men (9). These abnormalities included reduced CMRglc, increased Aβ accumulation, and gray and white matter loss in key brain regions for AD, such as parieto-temporal, posterior cingulate, and frontal cortices.…”

Section: Imaging the Menopausal Brainmentioning

confidence: 99%

“…Recent translational brain imaging studies have found that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity (including reduced glucose metabolism and mitochondrial function) and increased brain amyloid-beta deposition (Aβ, a hallmark of AD pathology) as compared to premenopausal women and age-matched men (8, 9). These findings substantiate the eclipsing effects of endocrine aging on chronological aging in the female’s brain several years, if not decades, before possible clinical symptoms emerge and the progressively increased risk of AD in women due to MT (6).…”

Section: Alzheimer’s Disease Risk and Female-specific Hormonal Changesmentioning

confidence: 99%

“…Recent brain imaging studies have investigated AD risk during endocrine transition states in clinically and cognitively normal women and men to characterize sex-dependent emergence of an AD endophenotype, characterized by Aβ deposition (11C-PiB PET), glucose hypometabolism (18F-FDG PET) and brain atrophy (MRI) (9). …”

Section: Imaging the Menopausal Brainmentioning

confidence: 99%

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Female Sex and Alzheimer’s Risk: The Menopause Connection

et al. 2018

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Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer’s disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.

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Section: Imaging the Menopausal Brainmentioning

confidence: 98%

Section: Imaging the Menopausal Brainmentioning

confidence: 99%

Section: Alzheimer’s Disease Risk and Female-specific Hormonal Changesmentioning

confidence: 99%

Section: Imaging the Menopausal Brainmentioning

confidence: 99%

See 2 more Smart Citations

Female Sex and Alzheimer’s Risk: The Menopause Connection

et al. 2018

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“…Females exhibit an AD endophenotype characterized by the brain hypometabolism, loss of gray and white matter, and elevated depositions of Aβ [47, 48]. Therefore, females experience higher age-specific AD death rates [49].…”

Section: Endocrinal Dysregulations In the Ad Pathophysiologymentioning

confidence: 99%

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad

Fatima

Mondal³

2019

Neuropsychobiology

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Alzheimer’s disease (AD), the commonest progressive neurodegenerative disorder of the brain, is clinically characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies suggest a relationship between the endocrinal dysregulation and the neuronal loss during the AD pathology. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis regulating circulating levels of glucocorticoid hormones has been implicated in the pathophysiology of AD. Likewise, dysregulated insulin signaling, impaired glucose uptake and insulin resistance are some of the prime factors in the onset/progression of AD. In this review, we have discussed the changes in HPA and HPG axes, implicated insulin resistance/signaling and glucose regulation during the onset/progression of AD. Therefore, simultaneous detection of these endocrinal markers in the early or presymptomatic stages may help in the early diagnosis of AD. This evidence for implicated endocrinal functions supports the fact that modulation of endocrinal pathways can be used as therapeutic targets for AD. Future studies need to determine how the induction or inhibition of endocrinal targets could be used for predictable neuroprotection in AD therapies.

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Association of Bilateral Salpingo-Oophorectomy Before Menopause Onset With Medial Temporal Lobe Neurodegeneration

et al. 2019

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Key Points Question Do women who underwent bilateral salpingo-oophorectomy before menopause show greater medial temporal lobe structural changes, β-amyloid accumulation, and white matter lesion load on neuroimaging later in life compared with a control group? Findings In this case-control study, women with bilateral salpingo-oophorectomy before menopause had smaller amygdala volumes, thinner parahippocampal-entorhinal cortices, and lower entorhinal white matter fractional anisotropy values compared with control participants. Meaning Abrupt hormonal changes associated with bilateral salpingo-oophorectomy in premenopausal women may lead to medial temporal lobe structural abnormalities later in life; because alterations in structural imaging biomarkers of the medial temporal lobe neurodegeneration may precede clinical symptoms of dementia, longitudinal follow-up of this cohort with cognitive testing is necessary.

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Sex differences in Alzheimer risk

Cited by 221 publications

References 43 publications

Female Sex and Alzheimer’s Risk: The Menopause Connection

Female Sex and Alzheimer’s Risk: The Menopause Connection

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Association of Bilateral Salpingo-Oophorectomy Before Menopause Onset With Medial Temporal Lobe Neurodegeneration

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