Early detection of possible cognitive decline (PwCD) is crucial for preserving function and independence in aging. Objective:To examine whether dual-task and functional assessment tools can help detect cognitive impairment in older adults without prior diagnosis of neurocognitive disorders. Methods:A cross-sectional study was conducted with healthy older adults (≥60 years). The following exclusion criteria were adopted: neurological diseases with motor deficits, severe functional limitations, mobility aid use, and inability to walk six meters unaided. Assessments included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Drawing Test (CDT), Verbal Fluency (VF), Pfeffer Functional Activities Questionnaire, Timed Up and Go (TUG), Sit-to-Stand Test (STS), Berg Balance Scale (BBS), Step Test, and dual-task TUG (TUGdt) using animal naming (TUGdt-NA) and serial subtraction (TUGdt-S7). Statistical analyses included t-tests, Mann-Whitney U, ꭓ2 tests, and logistic regression (p≤0.05). Results:Among 144 participants, 89 were classified as healthy and 55 as PwCD. Most were female (90.9%), black (57.7%), with an average of 11.04 years of education. Groups did not differ in age, gender, or comorbidities. The PwCD group had lower education (p=0.01), more black individuals (p=0.03), and scored significantly worse on all cognitive tests (p<0.0001) and TUGdt (NA: p=0.040; S7: time p=0.027; accuracy p<0.001). No differences were found in STS, Step Test, BBS, or total Pfeffer scores; however, the PwCD group showed greater instrumental activities of daily living (IADL) impairment. Conclusion:The ability to perform dual tasks appears to be associated with functional capacity.
ABSTRACT. Managing neuropsychiatric symptoms is crucial in dementia. The Neuropsychiatric Inventory-Distress (NPI-D) assesses caregiver distress, and the Zarit Burden Interview (ZBI) evaluates overall burden. Objective: This meta-regression examined the relationship between ZBI and NPI-D with NPI total scores to explore how burden relates to caregiver distress and neuropsychiatric symptoms. Methods: After a systematic review of studies addressing neuropsychiatric symptoms and caregivers’ burden in people with dementia, a meta-regression was conducted to examine the association between NPI-D and ZBI scores and NPI total scores. We used data from five studies reporting NPI-D scores and seven reporting ZBI scores. Single-arm meta-analyses for NPI-D, NPI total, and ZBI scores were performed using a random-effects model. Results: The random-effects model estimated a mean ZBI score of 23.76 [95% confidence interval - 95%CI 14.32-33.20, I2=100%, p=0]. NPI-D scores had a mean of 10.09 [95%CI 6.56-13.63, I2=96%, p<0.01], and the mean NPI total score was 21.84 [95%CI 19.31-24.38, I2=95%, p<0.01]. The meta-regression between NPI-D Mean and NPI total scores showed a statistically significant relationship, with a coefficient of 1.32 [95%CI 0.97-1.68, p=0.000], indicating a strong association between caregiver distress and neuropsychiatric symptoms. Conclusion: Single-arm studies suggest a positive relationship between neuropsychiatric symptoms and caregiver burden. The meta-regression analysis between NPI-D and NPI total demonstrates a significant link between caregiver distress and neuropsychiatric symptoms. Future studies should develop precise tools capturing caregivers’ challenges and burden. PROSPERO: CRD42024567953
ABSTRACT. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a valuable tool for molecular mapping in neurological disorders. This scoping review synthesized current evidence on its use in proteomic analysis of neural tissues in Alzheimer’s disease (AD). From 1,419 screened records, 26 studies met the inclusion criteria. Findings highlight MALDI-MS’s capacity to detect beta-amyloid (Aβ) proteoforms, and tau protein post-translational modifications linked to AD. Its high spatial resolution enables region-specific molecular profiling, enhancing understanding of AD pathophysiology and supporting early biomarker discovery. The review underscores the translational potential of MALDI-MS in advancing targeted therapeutic development.
ABSTRACT Functional decline in activities of daily living (ADL) is considered a marker of ageing and Alzheimer’s disease. However, there is a lack of performance-based instruments specifically designed to assess ADL in adults and older adults with Down syndrome. Objective: To describe the adaptation process of the Direct Assessment of Functional Status (DAFS) to assess the functional capacity of adults with Down syndrome. Methods: The Direct Assessment of Functional Status-Brazilian Version (DAFS-BR) was administered to 15 adults with Down syndrome (nine men and six women) who were divided into two diagnostic groups: stable cognition and suspected dementia or cognitive impairment. The process was conducted in two phases: phase one was characterized by an adaptation in the tasks. In phase two, (cultural and semantic) equivalences were verified, as well as structural aspects, including layout and instructions. This phase was essential for verifying the applicability and comprehensibility of newly adapted tasks Results: The DAFS-BR was adapted for the time orientation, communication (telephone use), moneyhandling skills, and shopping skills domains, considering the target population. Conclusion: The adaptation process of the DAFS-BR for people with Down syndrome was made considering linguistic, psychological, and cultural idiosyncrasies in the target population, with the input of experts with relevant experience in each domain. After psychometric studies, the Direct Assessment of Functional Status-Down Syndrome (DAFS-DS) could be considered the first ecological instrument for evaluating functional status in adults with Down syndrome in Brazil to enhance both clinical practice and research.
Emotional functioning plays a key role in well-being and healthy ageing. The Positive and Negative Affect Schedule (PANAS) is one of the most widely used tools to assess affective dimensions, but few studies have validated its psychometric properties in older adults in Argentina. Objective:To validate the factorial structure and psychometric properties of the PANAS in a sample of non-institutionalised older Argentine adults. Methods:A total of 206 participants aged 60-91 years completed the PANAS along with measures of emotional, psychological, and social well-being, life satisfaction, and depression. Confirmatory factor analysis was performed to test the bifactorial structure of positive affect (PA) and negative affect (NA), and reliability was assessed using Cronbach's α and McDonald's ω. Results:The two-factor model showed excellent fit to the data (Comparative Fit Index=0.98; Root Mean Square Error of Approximation=0.06), supporting the distinction between PA and NA. Internal consistency was high for both dimensions (α and ω>0.80). As expected, PA correlated positively with emotional and personal well-being and life satisfaction, whereas NA correlated negatively with these variables and positively with depressive symptoms. Conclusion:The findings confirm the validity and reliability of the PANAS in older Argentine adults. This instrument demonstrates a robust bidimensional structure and consistent associations with relevant psychological constructs, supporting its use for assessing affective dimensions in research and clinical contexts involving ageing populations.
Advances in healthcare have led to increased life expectancy among individuals with Down syndrome, resulting in a growing population of older adults within this group. As a result, the prevalence of cognitive decline and dementia has increased, largely due to the genetic predisposition of Down syndrome to early and significant accumulation of brain amyloid and intensified formation of neurofibrillary tangles. Early detection of functional alterations, particularly those related to gait and balance, may serve as a valuable clinical marker of emerging neurocognitive impairment. Objective:To synthesize the current evidence on the relationship between gait, cognitive decline, and dementia in adults and older adults with Down syndrome. Methods:A systematic search was conducted in the PubMed database in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Original observational studies evaluating gait, balance, or fall risk in relation to cognitive decline or dementia in adults with Down syndrome were included. Methodological quality was assessed using the Joanna Briggs Institute critical appraisal tools. Results:Thirty-seven records were identified, of which five original studies met the inclusion criteria. Overall, the findings suggest an association between gait alterations, balance, and cognitive decline in individuals with Down syndrome. Commonly reported abnormalities included reduced gait speed, increased gait variability, inconsistency in gait parameters, and impaired balance. However, heterogeneity in study design, different measurement protocols, and small sample sizes limited the comparability and generalizability of the results. Conclusion:Gait assessment holds promise as a non-invasive, accessible approach for early identification of cognitive decline in individuals with Down syndrome. Future research should prioritize longitudinal designs, standardized assessment protocols, and larger representative samples to inform targeted and evidence-based clinical interventions.
Aphasia is a neurological condition characterized by partial or total loss of verbal communication, most commonly caused by stroke. In hospital settings, brief and reliable tools are essential to identify and quantify aphasia early, enabling prompt diagnosis and appropriate rehabilitation planning. However, Brazil lacks language assessment instruments adapted for bedside use. Objective:To perform the cross-cultural adaptation and validation of the Bedside Language test for Brazilian Portuguese. Methods:The BL underwent translation, back-translation, expert review, and cultural adaptation. The final version was administered to 70 participants. Two evaluators applied the instrument on the same day to assess inter-rater reliability, and the same examiner reapplied it within two days to assess test-retest reliability. The Bedside Evaluation Screening Test (BEST-2) language test was also used for concurrent validity. Results:The Brazilian version of the BL demonstrated high internal consistency (Cronbach's alpha: spontaneous reading - LE=0.80; comprehension - CO=0.86; repetition - RE=0.95; writing - ES=0.73; overall=0.87), as well as satisfactory intra-rater (p=0.22) and inter-rater (p=0.77) reliability. It showed a strong correlation with the BEST-2 across all linguistic domains except writing. Conclusion:The Brazilian Portuguese version of the BL is a brief, valid, and reliable bedside screening tool for identifying aphasia in patients with ischemic stroke, supporting high-quality care in specialized stroke centers.
The rapid growth of India's elderly population necessitates understanding the determinants of cognitive health. Objective:This study examined the prevalence of cognitive impairment and its association with socio-demographic, health, and behavioural factors among community-dwelling older adults in urban Delhi. Methods:A community-based cross-sectional study was conducted from January to June 2023 among 290 adults aged ≥60 years in South-West Delhi, selected through multistage sampling. Data on socio-demographics, health status, and lifestyle were collected via structured interviews. Cognitive function was assessed using the Brief Interview for Mental Status (BIMS) and classified as intact, mild to moderate, or severe impairment. Principal Component Analysis (PCA) identified explanatory dimensions; multivariable ordinal logistic regression examined associations; and K-means clustering grouped participants by cognitive profiles. Results:Overall, 52.8% had intact cognition, 37.2% mild to moderate impairment, and 10% severe impairment. Severe impairment was most prevalent among those aged ≥81 years (61.5%) and with no formal education (55.2%), while intact cognition was highest among skilled workers (26.6%) and those with high school or higher education (43.8%). Significant factors included age, education, body mass index (BMI), physical activity, smoking, alcohol use, dietary intake, sleep quality, mental activity, and social engagement (all p<0.001). PCA yielded eight principal components capturing behavioral, health, and socio-demographic domains. K-means clustering identified two distinct cognitive profiles based on performance and associated factors. Conclusion:Cognitive status in older urban adults is shaped by modifiable health and lifestyle factors. Community-based interventions promoting physical activity, social participation, and healthy behaviors may help preserve cognition in aging populations.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease affecting various cognitive domains, requiring a holistic and integrated therapeutic approach. The treatment of AD goes beyond pharmacological interventions, also necessitating non-pharmacological therapies that can act synergistically, both with each other and with emerging pharmacological treatments, including new anti-amyloid therapies. These therapies aim to improve patients' quality of life and alleviate behavioral symptoms, such as agitation and depression, and delay disease progression. Current clinical and meta-analytic evidence suggests that these approaches can be effectively integrated with conventional treatment, offering a valuable alternative to enhance patients' overall well-being. However, further research is needed to deepen the understanding of the ideal combination of the new anti-amyloid therapies, to address the limitations of current evidence, and to robustly establish their effectiveness in the clinical context of AD, aiming to generate a broader and more lasting impact on disease treatment. This narrative review aims to synthesize the evidence on diverse non-pharmacological therapies for managing AD and discuss their practical implications for clinical care.
Othello syndrome (OS) is characterized by pathological jealousy toward one's spouse, usually marked by delusions of infidelity. We report the first case of OS in Brazil, similar to the case described by Alzheimer in 1906, in a 54-year-old right-handed patient diagnosed with Alzheimer's disease (AD). The diagnostic workup included a clinical history and a positive family history of dementia, the Clinical Dementia Rating (CDR) scale, the Edinburgh Handedness Inventory, and the Mini-Mental State Examination (MMSE). Electroencephalography revealed slow waves predominantly in the bilateral temporo-frontal regions. Cranial computed tomography showed diffuse cortico-subcortical atrophy compatible with the patient's age, as well as bilateral globus pallidus calcifications. Cerebral single-photon emission computed tomography revealed hypoperfusion in the medial frontal and bilateral temporal regions, more pronounced on the left - particularly in the inferomedial portion of the left temporal lobe - along with mild supratentorial ventricular dilatation. Postmortem examination revealed moderate bilateral fronto-temporo-parietal atrophy, and microscopy showed the presence of senile plaques and neurofibrillary tangles. We report an unusual case of OS as the initial clinical manifestation, later diagnosed as AD.
Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major contributors to dementia, with growing prevalence in Latin America. Evidence suggests that gut microbiota alterations may influence neurodegeneration, but data on Hispanic population are lacking. Objective:Characterize gut microbiota in individuals with AD, MCI, and controls in the Dominican Republic, exploring clinical, demographic, and dietary associations. Methods:Prospective-translational study including 88 participants aged ≥60 years. Performed clinical, cognitive, and functional assessments. Stool samples analyzed using 16S rRNA gene sequencing. Bioinformatic processing using Quantitative Insights into Microbial Ecology Version 2 (QIIME2) and R. Alpha and beta diversity, taxonomy, and differential abundance were evaluated. Dietary influences were assessed using PERMANOVA. Results:No significant differences in alpha diversity (Shannon index 4-5, Simpson index 0.94-0.99, p>0.05) or beta diversity (p>0.05) were observed between groups. Firmicutes (51.9%) and Bacteroidota (34.1%) dominated the microbiota. Higher Desulfobacterota abundance in MCI and AD (0.54 and 0.61%, respectively, vs. 0.34% in controls; p<0.05). The Firmicutes/Bacteroidota ratio was lower in men with MCI (1.09) compared to controls and AD (1.70). MCI and AD were associated with increased levels of the genera Bilophila, Odoribacter, and Parabacteroides (p<0.05) and reduced levels of Mitsuokella and Eubacterium ruminantium. Dietary interactions, e.g., mango, lettuce, and carrot, influenced specific taxa (p<0.05). Conclusion:This study pioneers gut microbiota characterization in AD and MCI in the Dominican Republic, identifying microbial alterations in cognitive impairment and highlighting regional dietary and ethnic factors. Longitudinal and multi-omics studies are warranted to clarify causality and therapeutic potential.
ABSTRACT Crossed aphasia is a rare form of aphasia in right-handed individuals with right-hemisphere lesions. We report a man aged 67 years who developed crossed aphasia after a right posterior cerebral artery infarction involving the occipital lobe, thalamus, and medial parietal lobe. Neurological and neuropsychological examinations revealed mild anomic aphasia with preserved repetition and comprehension, left homonymous hemianopia, unilateral spatial neglect, prosopagnosia, and no apraxia. Writing showed a marked script-specific dissociation: kana writing was intact, whereas kanji writing was severely impaired and dominated by recall-failure errors (>90%), with few orthographic or component errors. One-year follow-up using the same language and writing tasks demonstrated partial improvement in accuracy but a stable error profile dominated by recall failures. This rare case indicates that selective kanji agraphia can occur in crossed aphasia due to right-hemisphere lesions and suggests impaired access to the visual orthographic lexicon with atypical hemispheric lateralization of writing functions in Japanese.
ABSTRACT The study of subjective well-being (SWB) is fundamental to positive psychology, being considered a potential protective factor for health and the maintenance of cognitive reserve during aging. Despite international evidence, there are gaps in the Brazilian literature regarding how specific components of SWB relate to different cognitive domains. Objective: To analyze the relationship between subjective well-being and cognitive performance in cognitively healthy Brazilian older adults. Methods: A longitudinal study was conducted with 183 older adults (mean age 67.3 years). Scales for General Life Satisfaction (SGV), Domain-Referenced Life Satisfaction (SVRD), and the Positive and Negative Affect Scale were applied. Cognitive performance was assessed using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) and the Mini-Mental State Examination (MMSE). Data were analyzed via Spearman’s correlation matrix. Results: The sample showed a female predominance and high educational level (mean of 17 years). Participants exhibited high levels of SWB and good cognitive performance. General life satisfaction correlated positively with the MMSE and the attention/orientation domains of the ACE-R. Satisfaction with mental capacity (SVRD_Mental) showed a significant correlation with global performance in both cognitive tests. However, no significant correlations were found between affect states (positive or negative) and cognition in this sample. Conclusion: Healthy, highly educated older adults exhibit high levels of subjective well-being and satisfactory cognitive performance. The results reinforce the association between life satisfaction and cognitive reserve, suggesting that SWB may act as a marker of successful aging.
ABSTRACT Neuropsychiatric symptoms (NPS) are common in dementia and may hinder differential diagnosis between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD). Despite investigations of NPS and social cognition, particularly Theory of Mind (ToM) and emotion recognition, their precise, differential impact on social cognition in bvFTD versus AD remains less characterized. Objective: This study examined NPS in bvFTD and their association with social cognition, comparing results to AD. Methods: Patients with bvFTD (n=13) and AD (n=18) were assessed using neuropsychiatric and cognitive batteries measuring depression, anxiety, mania, and psychosis. Social cognition was evaluated with the Mini-Social and Emotional Assessment (mini-SEA), including the Faux-Pas test (ToM) and the Facial Emotion Recognition Test (FERT). Results: The groups did not differ in sex, education, or disease duration. Compared to AD, bvFTD patients had higher manic symptoms (p<0.001) and schizophrenia spectrum symptoms, particularly in negative (p<0.001) and resistance/hostility (p=0.034) symptoms. In bvFTD, depressive (p=0.020) and anxious (p=0.045) symptoms positively correlated with the Faux-Pas test, while positive psychotic symptoms correlated negatively (p=0.005). In AD, obsessive-compulsive (p=0.013) and disorganized psychotic symptoms (p=0.009) negatively correlated with the Faux-Pas test, while manic symptoms negatively correlated with the FERT (p=0.033). Conclusion: bvFTD patients displayed more schizophrenic and manic symptoms than AD, with NPS impacting social cognition differently in each condition.
ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia worldwide, creating substantial clinical and socioeconomic burdens. Randomized controlled trials (RCTs) provide the highest level of evidence to evaluate interventions, yet global publication trends and thematic evolution have not been systematically analyzed. Objective As far as we are aware, there has been no bibliometric analysis that has thoroughly assessed RCTs in AD, despite their pivotal influence on the development of treatment and prevention strategies. Therefore, in this study, we conducted a bibliometric mapping analysis of global RCTs on AD. Methods A bibliometric analysis of human RCTs on AD from September 2010 to September 2025 was conducted using PubMed and Web of Science. VOSviewer was employed for keyword co-occurrence, co-authorship mapping, and co-citation analyses to identify research themes, collaborations, and temporal trends. Results A total of 4,482 RCTs were identified, revealing five main themes: pharmacological interventions, lifestyle and prevention strategies, pathophysiological mechanisms, cognitive and behavioral interventions, and clinical trial methodology. After 2015, focus shifted from traditional pharmacology to multidomain, prevention-oriented, and precision-driven approaches. Emerging topics included digital health, gut microbiome, and machine learning. Collaboration networks highlighted the dominance of the US and Europe, with rapid growth in Asia and emerging regions. Conclusion Findings indicate a paradigm shift in AD RCTs toward integrative, technology-enabled designs, emphasizing both pharmacological and non-pharmacological strategies. These trends can guide future global research priorities and intervention development.
ABSTRACT With population aging, the prevalence of cognitive deficits increases, highlighting the importance of nonpharmacological interventions for promoting mental health in older adults. Objective: To evaluate the efficacy of a remote cognitive stimulation program (Mentes Ativas) in cognitively healthy older adults. Methods: The initial sample included 56 participants enrolled in the USP 60+ program at the School of Arts, Sciences, and Humanities of the University of São Paulo. For the final analyses, 22 participants who completed at least 80% of the sessions over a six-month period were assessed. Assessments included the Geriatric Depression Scale, Geriatric Anxiety Inventory, Cognitive Function Instrument, and Satisfaction with Life Scale. Data were collected at baseline and post-intervention and analyzed using non-parametric statistical tests. Results: There was a significant reduction in perceived subjective cognitive decline (mean score from 4.07 to 3.07; p=0.005) and in depressive symptoms (3.55 to 2.32; p=0.046), as well as a decrease in anxiety symptoms (5.88 to 3.95) and slight improvement in life satisfaction (7.59 to 7.95), although not statistically significant (p=0.132). Significant correlations were found among greater perceived cognitive decline, both depressive and anxiety symptoms, and with lower life satisfaction. Conclusion: The Mentes Ativas program may help promote cognitive and psychosocial improvements in older adults, reinforcing the role of cognitive interventions in promoting healthy aging.
ABSTRACT Vanishing white matter (VWM) disease is a leukodystrophy caused by mutations in EIF2B1–5 genes, which impair cellular stress responses and protein synthesis regulation, leading to astrocytic dysfunction and white matter degeneration. While typically a pediatric condition, adult-onset cases are increasingly recognized. We report a 39-year-old Brazilian woman with a six-year history of progressive cognitive decline, gait impairment, and rapid deterioration following an infection. Neurological examination revealed spastic tetraparesis and severe cognitive impairment. Brain magnetic resonance imaging (MRI) showed diffuse white matter abnormalities with cystic degeneration. Whole-exome sequencing identified a homozygous EIF2B3 c.260C>T (p.Ala87Val) variant, previously associated with a founder effect in Quebec but not reported in Brazil. This case highlights the phenotypic variability of VWM, stress-triggered exacerbations, and the importance of genetic testing in adult patients with cognitive decline. It also expands the genotypic diversity of VWM in Brazil and underscores the need for multidisciplinary care.
ABSTRACT The diagnosis of Alzheimer’s disease (AD) based on biomarkers of the pathological process represents a significant change from previous criteria, which required the presence of dementia for AD diagnosis. These new criteria create difficulties in disclosing the diagnosis of AD to asymptomatic individuals. A similar example exists in the history of cognitive and behavioral disorders, where the risk of developing dementia paralytica (DP), a form of neurosyphilis (NS), could be detected even in the asymptomatic phase. Treatment in this phase of DP or in its early symptomatic phase was successful due to the discovery of new therapeutic modalities and new evolutionary biomarkers, which are not yet widely available in AD. This type of biomarker was very important in NS and will certainly be in AD, allowing for faster and less expensive clinical trials.
