Amanda Carneiro Rodrigues

Background: Sex-specific vulnerability to Alzheimer's disease (AD) has been increasingly recognized, with menopause representing a decisive neuroendocrine transition. Estrogen and progesterone modulate synaptic plasticity, glucose metabolism, and amyloid-tau homeostasis, yet the impact of their decline and replacement remains controversial. AD biomarkers provide objective means to assess menopausal hormone therapy (MHT) mechanistic effects beyond cognitive endpoints. Objective: To determine how MHT influences validated AD biomarkers in peri- and postmenopausal women. Methods: A systematic review was conducted following PRISMA guidelines (PROSPERO CRD420251149404). PubMed, Embase, Web of Science, and Cochrane Library were searched through September 2025 for interventional and observational studies evaluating MHT and AD biomarkers after non-surgical menopause. Eligible biomarkers included cerebrospinal fluid (CSF) and plasma markers, and amyloid-, tau- or FDG-PET imaging. Study quality was assessed using RoB-2 and ROBINS-I tools, and evidence certainty with GRADE. Results: Fourteen studies met inclusion criteria. Early or continuous transdermal 17β-estradiol was linked with lower CSF and plasma p-tau181 and preserved glucose metabolism in AD-vulnerable cortical regions. Neuroimaging studies showed decreased amyloid deposition and sustained metabolic benefits years after discontinuation. Conversely, oral conjugated equine estrogens and estrogen-progestin regimens led to neutral or unfavorable biomarker trends, particularly when initiated more than five years after menopause. Conclusions: MHT's effects on AD biomarkers depend on timing, formulation and hormonal composition. Early transdermal estradiol appears to reinforce neuroprotective biomarker profiles, whereas delayed or combined therapies may nullify these benefits. Genotype-stratified trials with harmonized biomarker reports are needed to define optimal neuroprotective windows for women.

Background: Dementia contributes to morbidity and mortality in aging populations, with infectious diseases as frequent terminal events. In Brazil, data on causes of death in dementia and hospital-based end-of-life care are limited. Objective: To describe causes of death, clinical characteristics, and pharmacological treatment patterns during the last month of life among patients with dementia hospitalized in a geriatric hospital in São Paulo, Brazil. Methods: This retrospective observational study included all patients with clinically diagnosed dementia who died between 2015 and 2023 in a specialized geriatric hospital. Demographic, clinical, and pharmacological data were extracted from electronic medical records. Causes of death were classified using ICD-10 codes. Associations between dementia subtypes and infection-related deaths were evaluated using logistic regression adjusted for age, sex, and comorbidities. Statistical analyses were performed using R, with p < 0.05 considered significant. Results: A total of 122 patients were included (mean age 83.6 ± 7.4 years; 61.5% female). Alzheimer's disease was the most frequent subtype (52.5%), followed by vascular (26.2%) and mixed dementia (21.3%). Infectious diseases accounted for 67.2% of deaths, mainly pneumonia (48.3%) and sepsis (18.9%). Antibiotics were prescribed in 76.2% of cases, and antipsychotics in 58.1%. Palliative care measures were documented in 41.0% of cases. Conclusions: Infectious diseases were the most frequent causes of death among hospitalized patients with dementia, with high antibiotic use and limited palliative care documentation. These findings indicate the need for integrated end-of-life protocols and improved recognition of palliative needs.