Luciana Mascarenhas Fonseca

Objectives: The objective of this study is to investigate functional, cognitive, physical and nutritional outcomes in adults with intellectual disabilities (IDs), comparing individuals with and without Down syndrome from São Paulo, Brazil, and to evaluate the associations of group, degree of disability, age and sex with these outcomes. Additionally, we hypothesized that individuals with Down syndrome would present greater vulnerability to cognitive and physical decline compared to those with ID of other aetiologies. Method: This cross‐sectional observational study included 52 adults with ID divided into two groups: (1) 24 participants with Down syndrome (ID‐DS) and (2) 28 participants with non‐DS aetiologies (ID‐nonDS). Assessments included sociodemographic and clinical data; functional independence measure (FIM); physical performance (handgrip strength, 30‐s sit‐to‐stand test, gait speed test and MiniBESTest); nutritional status (Mini Nutritional Assessment [MNA]); cognitive function (Cambridge Cognitive Examination for Mental Disorders of the Elderly–Down Syndrome [CAMCOG‐DS]); cognitive decline (Informant Questionnaire on Cognitive Decline in the Elderly [IQCODE]); and functional activities (Pfeffer Questionnaire [QPAF]). Data were obtained through self‐report whenever possible, and proxy report (caregivers) when necessary, based on participants' communication abilities. Results: Compared with the ID‐nonDS group, the ID‐DS group demonstrated significantly poorer learning ( β = −2.56; p = 0.049) and remote memory performance ( β = −1.18; p = 0.011), a nonsignificant trend towards lower handgrip strength ( β = −4.68; p = 0.051) and more falls ( β = −0.39; p = 0.050). Sex and degree of disability were associated with several outcomes, whereas age showed no significant effect. Conclusion: Adults in the ID‐DS group exhibited cognitive and physical profiles suggestive of increased vulnerability to age‐related functional impairment compared with adults with other forms of ID. These findings should be interpreted cautiously due to the cross‐sectional design and sample size limitations. Replication in larger samples will be necessary to confirm these observations.

INTRODUCTION: Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of early AD‐related changes but remains understudied in DS. METHODS: Adults from the Alzheimer's Biomarker Consortium–DS (ABC‐DS) study ( N = 460, mean age 43.3 years; 45.7% female) were included. Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction. RESULTS: Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition. Exploratory analyses suggested sex‐specific interactions with tau outcomes. DISCUSSION: IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment.

Intraindividual cognitive variability (IICV) is a promising measure for early identification of dementia risk. Fewer studies have assessed IICV using high-frequency digital cognitive assessment or in populations with medical conditions. We aimed to characterize associations between IICV for reaction time and accuracy with plasma biomarkers of neurodegeneration (phosphorylated tau 181, phosphorylated tau 217, β-amyloid 42/40 ratio, glial fibrillary acidic protein, and neurofilament light chain) in individuals with Type 1 diabetes. We analyzed data from 114 participants from the Glycemic Variability and Fluctuations in Cognitive Status in Adults With Type 1 Diabetes study who provided blood samples (M = 48.9 years, range = 19-84). Cognition was assessed digitally at baseline and three times daily for 15 days via ecological momentary assessment. Hierarchical linear regression models examined associations between biomarkers and IICV, adjusting for demographics, glycemic variability, mean cognition, and nephropathy. Multiple testing correction used Benjamini-Hochberg. IICVs for reaction time at baseline and across repeated assessments were correlated and associated with β-amyloid 42/40, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau 217 (small to moderate effect size, p < .05), but associations did not remain significant after adjustment. Exploratory analyses indicated interactions with age and sex. IICV for accuracy was not associated with any biomarker. Although associations between IICV and plasma biomarkers were not robust after full adjustment, exploratory analyses suggested potential interactions with age and sex. The sample was predominantly non-Hispanic White, limiting the generalizability of our findings. These findings support continued investigation of digital IICV as a dynamic marker of early cognitive vulnerability. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Unquestionably, with the increase in life expectancy, dementia has become a significant health issue in Down syndrome (DS). However, in at least a subset of these individuals, cognitive aging can be considered normal, with absence of dementia symptoms even in the presence of Alzheimer's neuropathology. Therefore, it is essential to understand the complex interactions between risk and protective factors for dementia in this population. Studies are needed to address and elucidate those factors that may improve resilience against cognitive deterioration. Cognitive reserve (CR) is a theoretical construct proposed to explain variability in responses despite similar brain insults. Research addressing CR proxies in people with intellectual disability is limited; evidence is mostly derived from literature reviews or extrapolations from other populations. The present study aims to explore the association between specific proxies of CR and the occurrence of cognitive decline and dementia among adults with DS. Two complementary methodologies were adopted: a retrospective and observational study and a cross‐sectional study involving aging adults with DS. Severe levels of intellectual disability and older age were associated with a higher prevalence of cognitive decline or dementia. We observed a correlation between some proxies of CR. Previous engagement in occupational activities was correlated with regular school attendance, and higher parental education was associated with increased literacy in individuals with Down syndrome. The level of intellectual disability was associated with cognitive decline. Previous engagement in occupational activities and regular school attendance were identified as factors that may be associated with the construct of cognitive reserve and deserve future investigation. Higher parental education was a potential parameter that appears to affect the literacy of their child with trisomy 21.

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.

Published Version: This article has been peer-reviewed and published in Alzheimer’s & Dementia. Please cite the published version:Fonseca LM, Beeri MS, Hawks ZW, Jung L, Cleveland M, Delgado N, Bulger J, Grinspoon E, Janess K, Sliwinski MJ, Weinstock RS, Chhatwal JP, Kivisäkk P, Germine LT, Chaytor NS. ATN blood biomarkers are related to digital cognitive assessment in type 1 diabetes. Alzheimers Dement (Amst). 2024 Oct 23;16(4):e70029. doi: 10.1002/dad2.70029. PMID: 39445343; PMCID: PMC11497176.https://doi.org/10.1002/dad2.70029INTRODUCTION, Associations between Amyloid-Tau-Neurodegeneration (ATN) plasma biomarkers and cognition have not been characterized in adults with type 1 diabetes (T1D).METHODS, Using data from participants in the Glycemic Variability and Fluctuations in Cognitive Status in Adults with T1D study (N=114), associations between phosphorylated tau (pTau)181, pTau217, β-amyloid 42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) and cognition measured by self-administered digital tests were investigated with adjustments for age, sex, education, comorbidities (e.g. kidney disease), and glycemic indices. RESULTS, Higher concentrations of pTau181 and GFAP were associated with slower responses on working memory tasks (pTau181: β=0.261 p=0.007; GFAP: β=0.175, p=0.036), and higher β-amyloid 42/40 ratio was associated with better vocabulary (β=0.260, p=0.009). Except for GFAP, these associations remained significant after adjustments. DISCUSION, Digital cognitive performance was associated with several ATN plasma biomarkers in T1D adults. Prospective studies are needed to understand the utility of these biomarkers in T1D.

Objective: Cognitive intra-individual variability (IIV) is a commonly used method to estimate how dispersed or inconsistent an examinee’s test scores are across measures that comprise a test battery, trial-by-trial responses on a single task, or across multiple testing sessions. Elevated IIV has been hypothesized to reflect a failure of executive control due to alterations in brain activity or central nervous system integrity. Measures of IIV have a rich history. Growing empirical evidence supports their construct validity and potential for research and clinical applications. However, guidelines for calculating, interpreting, and implementing IIV measures in clinical practice are lacking. Here, we outline the history of IIV and its use in clinical research, summarize metrics for its calculation, review psychometric limitations, and explore future avenues of investigation, with a specific focus on dispersion-based (i.e., variability across tasks) IIV. Methods: A narrative review and commentary on the literature. Conclusions: IIV reliably differentiates clinical populations from healthy groups and predicts disease progression, everyday functioning, and mortality. Questions pertaining to the optimal methodology for IIV, its cognitive architecture, and its incremental validity remain unanswered. We discuss the possibility of using IIV as an embedded measure of performance validity and in detecting pathologic change using ecological momentary assessments. The evidence suggests that IIV can be used as a method of neuropsychological inference. We conclude this review with recommendations for best practices for employing IIV measures in research.

INTRODUCTION: Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of glucose fluctuations on the aging brain remains unclear. We examined whether CVG is associated with plasma biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration. METHODS: Participants included N = 114 adults with type 1 diabetes assessed for processing speed and sustained attention using ecological momentary assessment (EMA) combined with continuous glucose monitoring (CGM). We characterized associations between CVG and amyloid beta (Aβ) 42/40, phosphorylated tau (p‐tau) 181 and 217, neurofilament light chain, and glial fibrillary acidic protein. RESULTS: CVG was associated with all plasma biomarkers, except Aβ 42/40. CVG for sustained attention exhibited strong associations with p‐tau biomarkers that persisted across covariate specifications. DISCUSSION: CVG may be a useful digital phenotype of AD. It remains unclear whether CVG contributes to versus arises from neurodegeneration. We consider possible mechanisms linking cognitive vulnerability and long‐term glucose variability to the development of neuropathology. Highlights: Cognitive vulnerability to glucose (CVG) may be a useful digital phenotype of neurodegeneration. We used cognitive ecological momentary assessment and continuous glucose monitoring to investigate CVG's associations with plasma biomarkers. Associations of CVG for sustained attention and phosphorylated tau 181 remained significant across covariates. We discuss possible mechanisms relating glucose variability, cognition, and neurodegeneration.

Inclusive research is a relatively new concept that has received attention in recent years as a scientific priority to respond to health disparities and maximize the practical implications of research. This approach involves a partnership between academics and the individuals who are experiencing the problem to be investigated. Despite the high incidence of dementia and asymptomatic Alzheimer’s disease in aging individuals with Down syndrome, inclusive research with this population or those with intellectual disability (ID) at risk of dementia is an area that is little approached and not well documented. Here, we describe the evolution of inclusive research on ID and dementia, some of the challenges and benefits of its implementation, and key aspects to consider when planning such studies. There is an urgent need for national and international guidelines to support inclusive research involving this population. Such frameworks should ensure accessibility, ethical rigor, the meaningful participation of co-researchers, ultimately advancing equity and scientific quality in this underrepresented field.