Lina Maria Zapata‐Restrepo

Biological aging clocks offer estimations of aging and dementia, yet scalability is limited. We introduce a large-scale, cross-national speech clock derived from 2928 individuals across five Latin American countries, spanning healthy controls (HCs), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and non-language/language-dominant frontotemporal dementia (nldFTD/ldFTD). Multimodal acoustic and linguistic features were trained with supervised models to estimate chronological age, generating speech age gaps (SAGs) as cross-sectional markers of deviations from chronological age, with positive values interpreted as relatively older-appearing speech profiles. SAGs differentiated diagnostic groups (HCs < patient groups, with AD < nldFTD < ldFTD). This pattern was associated with clinical/cognitive domains. SAGs correlated with phosphorylated tau (p-Tau217) in AD and social exposome in HCs and AD. Brain clocks (structural/functional/combined) were associated with SAG in AD, nldFTD, and ldFTD. Epigenetic age correlated with SAGs in HCs and AD across Hannum, Retroclock, and OMICmAge, whereas ldFTD associations were limited to Retroclock and OMICmAge. These results indicate that SAGs capture cross-sectional multilevel aging-related variation and may offer a scalable, culturally adaptable, low-cost biomarker candidate for research in underrepresented global settings.

Background: The global impact of COVID-19 restrictions on people with dementia (PWD) living at home and their informal caregivers has been described extensively. However, adoption of this knowledge into policy and practice is limited because of a lack of coordinated, inclusive, and regionally sensitive prioritization. Objective: To establish key regional research priorities for Europe and the Global South. Methods: Following consensus-based prioritization methods, we applied a three-step approach: 1) a systematic literature review to derive a list of topics describing how PWD and caregivers were impacted by the COVID-19 restrictions; 2) an online survey distributed to PWD, caregivers and health care professionals (HCP) across 14 countries asking respondents to select the 10 most important topics; and 3) an iterative consultation process with stakeholders from each country to translate the top-ranked topics into a research agenda. Results: We identified 51 quantitative and 18 qualitative relevant publications, from which we derived 38 topics. 29 PWD, 110 caregivers and 117 HCP across 14 countries prioritized these topics, which largely overlapped across stakeholder groups and countries. The top ranked priorities cluster into four themes: daily routine and physical function, mental health, disease progression, and access to care. The consultancy process with stakeholders resulted in three lines of research to address these themes: understanding mechanisms, designing and improving education, and information access. Conclusions: This research agenda offers a roadmap to guide future research and policy aimed at strengthening support for PWD and their caregivers in times of public health crises.

Background: Early‐onset Alzheimer's disease (EOAD) is a rare subtype of Alzheimer's, manifesting before age 65 and often linked to genetic mutations. This report describes the case of a 47‐year‐old Colombian man with EOAD and a novel pathogenic PSEN1 mutation, c.519G>T (p.Leu173Phe). Method: Case description. The patient presented with a one‐year history of progressive cognitive and behavioral decline, including memory impairment, disorientation, paranoia, and social withdrawal. A family history of EOAD in his mother and sister suggested a genetic etiology. Initial evaluations, including brain MRI and laboratory tests, were unremarkable, but neuropsychological testing and brain SPECT scan revealed significant cognitive deficits and hypoperfusion, consistent with EOAD. The patient experienced rapid progression of symptoms, including prosopagnosia, executive dysfunction, seizures, and behavioral disturbances. Despite symptomatic management with cholinesterase inhibitors, memantine, and antipsychotics, his condition deteriorated, culminating in severe dementia by age 55. Result: Whole‐genome analysis identified a novel likely pathogenic PSEN1 mutation (c.519G>T), which had not been previously reported. This variant, located in the third transmembrane domain of the PSEN1 protein, is hypothesized to disrupt γ‐secretase activity, contributing to EOAD pathogenesis. The case highlights the phenotypic variability associated with PSEN1 mutations, including cognitive and neuropsychiatric symptoms, seizures, and parkinsonism. It underscores the importance of genetic counseling and testing in suspected familial EOAD cases, particularly in populations with known genetic predispositions. Current treatments offer limited symptomatic relief, emphasizing the need for novel therapeutic approaches. Conclusion: This case of EOAD with a novel PSEN1 mutation highlights the importance of early genetic and neuropsychological evaluations for diagnosis and management. Collaborative research is essential to advance understanding and develop effective treatments for rare neurodegenerative diseases.

Early-onset Alzheimer’s disease (EOAD) is a rare form of dementia that often progresses more quickly than late-onset cases, and is more commonly associated with autosomal dominant mutations. A 47-year-old male presented with progressive cognitive and behavioral decline, a family history of EOAD, and was later found to have a novel pathogenic PSEN1 variant (c.519 G > T, p.Leu173Phe). Initial evaluations, including neuroimaging and laboratory tests, were unremarkable. Neuropsychological testing later revealed memory impairment, executive dysfunction, and neuropsychiatric symptoms. These features, alongside the identified mutation, are consistent with phenotypic presentations of EOAD involving the third transmembrane domain of PSEN1. Pharmacological treatment with cholinesterase inhibitors and antipsychotics yielded limited benefit. Notably, the extended follow-up time, of more than 10 years from the early symptomatic stage, is a unique and valuable feature of this case study, providing rare longitudinal insight into the natural course of genetically confirmed EOAD.

The rising prevalence of dementia, particularly in low-income and developing countries, highlights the urgent need for effective cognitive screening tools. However, the existing tools often fail to address the unique needs of low-educated and illiterate populations, leading to diagnostic disparities. This review aimed to evaluate cognitive screening tests and domains employed globally to detect mild cognitive impairment (MCI) and dementia in low-educated and illiterate older adults. Following the PRISMA guidelines, Searches were performed in Web of Science, Scopus, and PubMed, targeting studies from January 2000 to 2023 involving adults over 45 years old. Of 1611 studies identified, 27 met the inclusion criteria and underwent pair review. The results revealed that most studies preferred adapting the existing tools to local languages over developing culturally tailored instruments. Twelve cognitive tests specifically designed for low-educated populations were identified, with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) being the most utilized, despite their educational biases. Adjusting the cutoff points improved detection (e.g., MoCA: sensitivity 82.5%, specificity 82%). Notably, the Rowland Universal Dementia Assessment Scale (RUDAS) demonstrated superior performance for low-educated groups (sensitivity 89% and specificity 93%). The findings underscore the critical need for region-specific cognitive batteries that integrate functional assessments, ensuring equitable and accurate diagnosis across diverse educational backgrounds.

Obsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long‐sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans‐ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans‐ancestry genomic analyses to accelerate the identification of OCD risk loci, fine‐map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

While age-specific dementia prevalence is falling in many countries, several recent reviews estimate prevalence in Latin America to be higher than anywhere else in the world. This may be, in part, due to the high incidence of socioeconomic and health-related risk factors present in the region. However, growing evidence suggests that primary and secondary prevention via modifiable risk factors is possible, and that 40% of cases may be mitigated through interventions which target modifiable risk. This suggests that there may be significant scope for dementia risk reduction in this region. In June 2021, eight fellows from the Global Brain Health Institute (GBHI) hosted an expert consensus workshop on challenges and opportunities for brain health and dementia prevention in Latin America. The workshop brought together 16 experts in dementia, aging, and brain health from a range of professional backgrounds and geographical regions. From this workshop we collated an expert-led consensus regarding the practical challenges and opportunities implicit in embedding brain health and dementia prevention initiatives in the Latin American context. Here we discuss the outcomes of this workshop, highlighting several challenges and opportunities and discussing how these may be addressed.

Background: Psychiatric manifestations are common in the behavioral variant of frontotemporal dementia (bvFTD) with many patients misclassified with other psychiatric diagnoses. In this study, we described the initial neuropsychiatric symptoms and the psychiatric misdiagnoses in a diverse population of patients with probable bvFTD seen at a psychiatric public hospital in Colombia.Methods: We retrospectively reviewed the medical records of 28 patients who met diagnostic criteria for probable bvFTD based on a multidisciplinary evaluation. Neuropsychiatric symptoms were rated using the NPI. Initial psychiatric diagnoses were made using the DSM‐V. The bvFTD diagnostic criteria of the international consortium were used. Stata 16.1 and SPSS 27.0 were used for the statistical analysis.Results: Using the NPI, we found that the most common symptoms were apathy in both genders. Delusions were present in 60.7% and hallucinations in 39.2% of the sample. 71.4% of the patients were misdiagnosed with psychiatric disease and not with dementia. In women, the most frequent psychiatric diagnoses were depression (26.3%), and bipolar disorder (26.3%), while in men it was anxiety disorders (33.3%) and psychotic disorders (22.2%).Conclusion: Psychotic symptoms were higher in this sample than in previous studies. The presence of psychiatric symptoms and their possible overlap in patients with bvFTD make differential diagnosis difficult. The misdiagnosis could be related to factors such as a lack of knowledge about this type of dementia in the medical community. In the future, the implementation of specific biomarkers and genetic testing will help to improve the diagnosis of bvFTD.

Objective: To describe the demographic characteristics, initial psychiatric diagnoses, and the time to reach a diagnosis of probable behavioral variant frontotemporal dementia (bvFTD) in a public psychiatric hospital in Cali, Colombia.Methods: We retrospectively reviewed the medical records of 28 patients who were diagnosed with probable bvFTD based on a multidisciplinary evaluation that included a structural MRI, neuropsychological testing, functional assessment, and neurological exam. Prior to this evaluation, all patients were evaluated by a psychiatrist as part of their initial consultation at the hospital. The initial consultation included the Neuropsychiatric Inventory and diagnoses based on the DSM-V. Demographics, clinical features, and initial psychiatric misdiagnoses were extracted from clinical records and summarized in the full sample and by gender.Results: The study sample had a mean education of 10.0 years (SD = 4.9) and 68.0% were female. In the full sample, 28.6% were initially diagnosed with dementia, and 71.4% with a psychiatric disorder. The psychiatric diagnosis at initial consultation differed by gender. Women were most likely to be diagnosed with depression (26.3%) or bipolar disorder (26.3%), while the men were most likely to be diagnosed with anxiety (33.3%) or a psychotic disorder (22.2%). Psychotic symptoms were common (delusions, 60.7% and hallucinations, 39.3%), and the pattern of neuropsychiatric symptoms did not differ by gender.Conclusions: This is one of few case series of bvFTD in a Colombian population, where bvFTD is a recognizable and prevalent disorder. In this psychiatric hospital, the majority of patients with bvFTD were initially diagnosed with a primary psychiatric condition. There was a gender difference in psychiatric diagnosis, but not in neuropsychiatric symptoms. In this sample, the rate of psychiatric misdiagnosis, as well as the psychotic symptoms, were higher compared to rates described in other countries. These results highlight the need for interventions to improve bvFTD diagnosis in under-represented populations.