Drug Development.

Background: Recruiting and retaining older adults for clinical trials is challenging, especially in low-resource settings. Such challenges led to a systematic exclusion of such participants from clinical trials, compromising the generalizability of the results obtained in high income countries.

Objective: Here we describe the strategies we used in the PROAME study for recruiting and retaining illiterate older adults from low socioeconomical levels in a non-pharmacological trial.

Dementia Care Research and Psychosocial Factors.

Background: Education is a recognized modifiable dementia risk factor. To boost cognitive reserve and reduce dementia risk in Brazil's vulnerable populations, we conceived a literacy program (PROAME trial) targeting low-educated adults, aiming to explore how executive function and individual differences influence program effectiveness.

Method: We screened 130 adults, with 108 meeting enrollment criteria.

Dementia Care Practice.

Background: The COVID-19 pandemic in Ethiopia posed additional challenges to an already strained mental health service. Eka Kotebe Hospital, the second-largest mental health facility with a capacity of 175 beds, was transformed into a dedicated COVID-19 treatment center, leaving mental health service users, especially vulnerable elderly patients with cognitive impairments, without adequate support. I had the challenge to implement alternatives to provide mental health services coverage to underserved elderly population.

Sex and the Clock: Exploring Sex Differences in Chronotype and Circadian Preferences Among Cognitively Healthy Older Adults.

This study aimed to compare objective circadian rest-activity-rhythm (RAR) measures with self-reported circadian behavior and morning-evening preference in cognitively healthy older men and women. A total of 129 participants (ages 65-90) completed the Horne & Ostberg Morning-Eveningness Questionnaire (MEQ) and the Circadian Type Inventory (CTI) to assess their morning-evening preference and circadian traits, including rigidity, vigor, languidness, and flexibility. These subjective measures were compared to objective actigraphy data from a sub-cohort of 70 individuals who wore actigraphy watches for 24 hours a day over a 7-day period.

Hypertension may associate with cerebral small vessel disease and infarcts through the pathway of intracranial atherosclerosis.

Hypertension, a major modifiable risk factor for cardiovascular diseases, is linked to late-life neurocognitive disorders such as vascular dementia and Alzheimer's disease (AD). This study explores the associations between hypertension, intracranial atherosclerotic disease (ICAD), cerebral small vessel disease (cSVD), and Alzheimer's disease neuropathologic change (ADNC) in a large community-based autopsy study. This cross-sectional study used data from the Biobank for Aging Studies of the University of São Paulo Medical School.

Comprehensive mapping of synaptic vesicle protein 2A (SV2A) in health and neurodegenerative diseases: a comparative analysis with synaptophysin and ground truth for PET-imaging interpretation.

Synaptic dysfunction and loss are central to neurodegenerative diseases and correlate with cognitive decline. Synaptic Vesicle Protein 2A (SV2A) is a promising PET-imaging target for assessing synaptic density in vivo, but comprehensive mapping in the human brain is needed to validate its biomarker potential. This study used quantitative immunohistochemistry and Western blotting to map SV2A and synaptophysin (SYP) densities across six cortical regions in healthy controls and patients with early-onset Alzheimer's disease (EOAD), late-onset Alzheimer's disease (LOAD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-GRN).

Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics.

The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14 that are disease specific.

Health literacy, but not memory, is associated with hippocampal connectivity in adults with low levels of formal education.

Introduction: The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood.

Methods: Thirty-five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test).

The Association Between Neuropathological Lesions and Body Mass Index Is Independent of Cognitive Abilities.

Background: The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy studies are key to detecting preclinical neurodegenerative and cerebrovascular diseases that could be underlying weight changes.

Objective: We investigated the association between dementia-related brain lesions and BMI and evaluated whether the cognitive function was a mediator of this association.

Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?

A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier.

Comorbid neuropathology and atypical presentation of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.

Methods: We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.

Insufficient evidence for an association between iatrogenic Alzheimer's disease and cadaveric pituitary-derived growth hormone.

A Nature Medicine paper published in January 2024 describes eight cases of iatrogenic Alzheimer's disease in individuals who received cadaveric pituitary-derived human growth hormone. The paper's conclusions argue for the transmissibility of Alzheimer's disease, which, if true, would create a significant public health crisis. For example, neurosurgical practices would require substantial revision, and many individuals who have undergone neurosurgical procedures would now be at considerable risk of Alzheimer's disease.

iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.

Background: Tau post-translational modifications (PTMs) result in the gradual build-up of abnormal tau and neuronal degeneration in tauopathies, encompassing variants of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Tau proteolytically cleaved by active caspases, including caspase-6, may be neurotoxic and prone to self-aggregation. Also, our recent findings show that caspase-6 truncated tau represents a frequent and understudied aspect of tau pathology in AD in addition to phospho-tau pathology.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

Episodic memory improvement in illiterate adults attending late-life education irrespective of low socioeconomic status: insights from the PROAME study.

Unlabelled: The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

Introduction: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care.

Methods: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.

Results: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted.

SV2A PET imaging in human neurodegenerative diseases.

This manuscript presents a thorough review of synaptic vesicle glycoprotein 2A (SV2A) as a biomarker for synaptic integrity using Positron Emission Tomography (PET) in neurodegenerative diseases. Synaptic pathology, characterized by synaptic loss, has been linked to various brain diseases. Therefore, there is a need for a minimally invasive approach to measuring synaptic density in living human patients.