Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias: The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil.

OBJECTIVE: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. METHODS: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. RESULTS: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. CONCLUSION: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

Bearded capuchin monkeys as a model for Alzheimer's disease.

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread ß-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of ß-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease.

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia.

Mental disorders are highly prevalent and important causes of medical burden worldwide. Co-occurrence of neurological and psychiatric symptoms are observed among mental disorders, representing a challenge for their differential diagnosis. Psychiatrists and neurologists have faced challenges in diagnosing old adults presenting behavioral changes. This is the case for early frontotemporal dementia (FTD) and bipolar disorder. In its initial stages, FTD is characterized by behavioral or language disturbances in the absence of cognitive symptoms. Consequently, patients with the behavioral subtype of FTD (bv-FTD) can be initially misdiagnosed as having a psychiatric disorder, typically major depression disorder (MDD) or bipolar disorder (BD). Bipolar disorder is associated with a higher risk of dementia in older adults and with cognitive impairment, with a subset of patients presents a neuroprogressive pattern during the disease course. No mendelian mutations were identified in BD, whereas three major genetic causes of FTD have been identified. Clinical similarities between BD and bv-FTD raise the question whether common molecular pathways might explain shared clinical symptoms. Here, we reviewed existing data on clinical and molecular similarities between BD and FTD to propose biological pathways that can be further investigated as common or specific markers of BD and FTD.