Examining the relationship between brain activation and proxies of disease severity using quantile regression in individuals at risk of Alzheimer's disease.

Previous studies have reported a pattern of hyperactivation in the pre-dementia phase of Alzheimer's disease (AD), followed by hypoactivation in later stages of the disease. This pattern was modeled as an inverse U-shape function between activation and markers of disease severity. In this study, we used quantile regression to model the association between task-related brain activation in AD signature regions and three markers of disease severity (hippocampal volume, cortical thickness, and associative memory). This approach offers distinct advantages over standard regression models as it analyzes the relationship between brain activation and disease severity across various levels of brain activation. Participants were 54 older adults with subjective cognitive decline+ (SCD+) or mild cognitive impairment (MCI) from the CIMA-Q cohort. The analysis revealed an inverse U-shape quadratic function depicting the relationship between disease severity markers and the activation of the left superior parietal region, while a linear relationship was observed for activation of the hippocampal and temporal regions. Quantile differences were observed for temporal and parietal activation, with more pronounced effects observed in the higher quantiles of activation. When comparing quantiles, we found that higher quantile of activation featured a greater number of individuals with SCD+ compared to mild cognitive impairment (MCI). Results are globally consistent with the presence of an inverse-U shape function of activation in relation to disease severity. They study also underscores the utility of employing quantile regression modeling as the modeling approach revealed the presence of non-homogeneous effects across various quantiles.

Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study.

Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia. Methods: This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points. Results: HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males. Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

Normative Data for the Judgment of Line Orientation Test (Long and Short Forms) in the Quebec-French Population Aged between 50 and 89 Years.

The Judgment of Line Orientation (JLO) Test of Benton assesses visuospatial processing without requiring motor skills. The test is frequently used in geriatric or brain-injured populations. As with other cognitive tests, performance on the JLO test may vary according to age, level of education, sex, and cultural background of individuals. The present study aimed to establish normative data for a short (15 items) and a long (30 items) form of the JLO. The sample for the short and long forms comprised 198 and 260 individuals, respectively, aged 50-89 years. All participants were French-speaking people from the province of Quebec, Canada. Using regression-based norming, the effects of age, years of formal education, and sex on JLO performance were estimated. The normative adjustment of the JLO short and long forms considered the weight of each predictor on test performance. Results indicated that JLO performance was positively associated with years of formal education and male sex, whereas it was negatively associated with age. Accordingly, normative data were generated using Z-scores and adjusted scaled scores derived from the regression equations. To conclude, the present norms will ease the detection of visuospatial impairment in French-Quebec middle-aged and older adults.

The SPECTRA Study: Validating a New Memory Training Program based on the Episodic Specificity Induction to Promote Transfer in Older Adults.

Some complex cognitive activities impacted by aging (future thinking, problem-solving, creative thinking) have been shown to rely on episodic retrieval, suggesting that cognitive interventions aiming to improve retrieval have the potential to induce transfer effects to these activities. Prior studies have shown that a brief one-session technique called Episodic Specificity Induction (ESI) can transiently improve episodic retrieval and induce transfer effects to complex tasks that rely on episodic retrieval in older adults. In the present proof-of-concept study, we assessed whether a training program consisting of repeated practice of the ESI technique can improve episodic retrieval and transfer to complex tasks. Fifteen healthy older adults completed a six-session intervention where they received repeated ESI practice. Before and after the intervention, nearest transfer effects were assessed using free recall, near transfer effects using recognition and associative recognition, and far-transfer effects using mean-ends problem-solving and divergent creative thinking. Before the intervention, typical ESI effects were observed (better performance after an ESI than after a control task), indicating that the ESI operated as expected in our sample. When examining the intervention effects, performance was increased after the intervention on free recall and recognition (nearest- and near-transfer) as well as problem-solving and divergent creative thinking (far transfer). These results indicate that an intervention relying on the ESI technique can produce both near and far transfer. These findings support the use of the ESI in the design of interventions that could improve retrieval and have a broad impact on a range of complex tasks.

Using co-creation focus groups to customise a remote multidomain programme designed to increase dementia literacy.

OBJECTIVES: To adapt the content and functionalities of Brain Health PRO, a web-based multidomain program designed to increase dementia literacy, to the context and needs of users, providers and community organisations across Québec, Canada. DESIGN: Five consecutive qualitative co-creation focus group sessions 30-90 min in duration each, exploring potential barriers and facilitators to usability, accessibility, comprehensibility, participant recruitment and retention. SETTING: Virtual meetings. PARTICIPANTS: A 15-member team based in Québec and Ontario, Canada, consisting of 9 researchers (including a graduate student and the project coordinator), representing occupational therapy, sensory rehabilitation, neuropsychology, psychology, health science and research methods, 3 informal caregivers of older adults living with cognitive decline and 3 members of the Federation of Quebec Alzheimer Societies. DATA ANALYSIS: Session recordings were summarised through both qualitative description and thematic analysis. RESULTS: The synthesised recommendations included adjustments around diversity, the complexity and presentation styles of the materials, suggestions on refining the web interface and the measurement approaches; it influenced aspects of participant recruitment, retention efforts and engagement with the content of Brain Health PRO. CONCLUSIONS: Co-creation in dementia prevention research is important because it involves collaboration between researchers, community support and service providers, and persons with lived experience as care providers, in the design and implementation of clinical studies. This approach helps to ensure that the content and presentation of educational material is relevant and meaningful to the target population and those involved in its delivery, and it leads to a greater understanding of their needs and perspectives.

Web-based cognitive assessment in older adults: Where do we stand?

PURPOSE OF REVIEW: The use of digital tools for remote cognitive measurement of older adults is generating increasing interest due to the numerous advantages offered for accessibility and scalability. However, these tools also pose distinctive challenges, necessitating a thorough analysis of their psychometric properties, feasibility and acceptability. RECENT FINDINGS: In this narrative review, we present the recent literature on the use of web-based cognitive assessment to characterize cognition in older adults and to contribute to the diagnosis of age-related neurodegenerative diseases. We present and discuss three types of web-based cognitive assessments: conventional cognitive tests administered through videoconferencing; unsupervised web-based assessments conducted on a computer; and unsupervised web-based assessments performed on smartphones. SUMMARY: There have been considerable progress documenting the properties, strengths and limitations of web-based cognitive assessments. For the three types of assessments reported here, the findings support their promising potential for older adults. However, certain aspects, such as the construct validity of these tools and the development of robust norms, remain less well documented. Nonetheless, the beneficial potential of these tools, and their current validation and feasibility data, justify their application [see Supplementary Digital Content (SDC), http://links.lww.com/CONR/A69 ].

Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.

BACKGROUND: Subjective cognitive decline (SCD) was proposed to identify older adults who complain about their memory but perform within a normal range on standard neuropsychological tests. Persons with SCD are at increased risk of dementia meaning that some SCD individuals experience subthreshold memory decline due to an underlying progression of Alzheimer's disease (AD). OBJECTIVE: Our main goal was to determine whether hippocampal volume and APOE4, which represent typical AD markers, predict inter-individual differences in memory performance among SCD individuals and can be used to identify a meaningful clinical subgroup. METHODS: Neuropsychological assessment, structural MRI, and genetic testing for APOE4 were administered to one hundred and twenty-five older adults over the age of 65 from the CIMAQ cohort: 66 SCD, 29 individuals with mild cognitive impairment (MCI), and 30 cognitively intact controls (CTRLS). Multiple regression models were first used to identify which factor (hippocampal volume, APOE4 allele, or cognitive reserve) best predicted inter-individual differences in a Face-name association memory task within the SCD group. RESULTS: Hippocampal volume was found to be the only and best predictor of memory performance. We then compared the demographic, clinical and cognitive characteristics of two SCD subgroups, one with small hippocampal volume (SCD/SH) and another with normal hippocampal volume (SCD/NH), with MCI and CTRLS. SCD/SH were comparable to MCI on neuropsychological tasks evaluating memory (i.e., test of delayed word recall), whereas SCD/NH were comparable to CTRLS. CONCLUSION: Thus, using hippocampal volume allows identification of an SCD subgroup with a cognitive profile consistent with a higher risk of conversion to AD.

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

BACKGROUND: Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. OBJECTIVES: To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. SETTING: University hospital. METHODS: A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. RESULTS: The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). CONCLUSIONS: The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Social Isolation of Older Adults Living in a Neighbourhood of Montreal: A Qualitative Descriptive Study of the Perspectives of Older Adults and Community Stakeholders.

The purpose of this study was to describe the social isolation of older adults in the Côte-des-Neiges neighbourhood (Montreal, Canada) from the perspectives of older adults and community stakeholders. To do so, a descriptive qualitative study was conducted, involving community-dwelling older adults and a variety of key stakeholders from the neighbourhood. Seven focus groups were held, with a total of 37 participants. Focus group transcripts were analyzed using the approach of Miles, Huberman, and Saldaña. Participants reported that social isolation of older adults is characterized by gaps in social interactions (scarcity of social interactions, lack of social support, and unsatisfying relationships) as well as by low social participation that can be depicted in three ways: (1) exclusion by society, (2) self-restriction of participation, and (3) low eagerness to socialize. This study highlights that there is a diversity in how social isolation of older adults manifests itself. It can be the result of a deliberate choice (or not), as well as being desired (or not). These aspects of the phenomenon of social isolation of older adults are still not well described. However, they offer relevant avenues for rethinking approaches to intervention development.

Trajectories of psychological distress during the COVID-19 pandemic among community-dwelling older adults in Quebec: A longitudinal study.

OBJECTIVE: The COVID-19 pandemic and its associated public health measures may increase the risk for psychological distress among vulnerable older adults. This longitudinal study aimed to identify predictors of psychological distress trajectories among community-dwelling older adults in Quebec, Canada. METHODS: The study spanned four time points across 13 months and three waves of the COVID-19 pandemic. The sample included 645 community-dwelling older adults ages 60 years and older in Quebec. Participants completed telephone-based interviews that included the Kessler 6-item Psychological Distress Scale (K6) to assess psychological distress at each time point as well as information on socioeconomic, medical, psychological and COVID-19 related factors. Group-based trajectory modelling was used to identify distinct trajectories of psychological distress across time. RESULTS: Three group-based trajectories of psychological distress were identified: the resilient (50.5%), reactive (34.9%), and elevated distress groups (14.6%). Individuals with mobility issues, insomnia symptoms, COVID-19 related acute stress, general health anxiety, increased loneliness symptoms, and those unable to use technology to see others were more likely to be in the reactive and elevated groups than the resilient group. Those with past mental health problems had uniquely increased odds of being in the reactive group compared to the resilient group. Individuals living in poverty and those who reported taking psychotropic medication had increased odds of being in the elevated distress group compared to the resilient group. CONCLUSION: These findings characterized distinct trajectories of psychological distress in older adults and identified risk factors for elevated distress levels.

Pre-frail older adults show improved cognition with StayFitLonger computerized home-based training: a randomized controlled trial.

Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether remote intervention is beneficial for older adults who are vulnerable or at risk of cognitive decline. In a 26-week multi-site, home-based, double-blind, randomized controlled trial, 120 cognitively healthy older adults (75 robust, 45 pre-frail; age range = 60-94) recruited from Switzerland, Canada, and Belgium were randomized to receive either the StayFitLonger (SFL) computerized multidomain training program or an active control intervention. Delivered on tablets, the SFL intervention combined adapted physical exercises (strength, balance, and mobility), cognitive training (divided attention, problem solving, and memory), opportunities for social and contributive interactions, and psychoeducation. The active control intervention provided basic mobilization exercises and access to video games. Cognitive outcomes were global cognition (Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults; ZAVEN), memory, executive function, and processing speed. Linear mixed model analyses indicated improved performance on the ZAVEN global cognition score in the SFL group but not in the active control group. Stratified analyses by frailty status revealed improved ZAVEN global cognition and processing speed scores following SFL in the pre-frail group but not in the robust group. Overall, the study indicates that a computerized program providing a multidomain intervention at home can improve cognition in older adults. Importantly, pre-frail individuals, who are at higher risk of cognitive decline, seem to benefit more from the intervention. Trial registration: ClinicalTrials.gov, NCT037519 Registered on January 22, 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04237519 .

Activation changes induced by cognitive training are consistent with improved cognitive reserve in older adults with subjective cognitive decline.

Functional magnetic resonance imaging (fMRI) was used to assess the effect of cognitive training on brain activation as a function of the learning phase and level of education. Forty older adults with subjective cognitive decline (SCD) received 6 1-hour memory training sessions with the method of loci. Brain imaging (N = 29) was measured during word list encoding and retrieval before training (PRE), after 3 training sessions (POST3), and after 6 training sessions (POST6). Participants showed increased activation of the left inferior pre-frontal gyrus from PRE to POST6 during encoding and reduced bilateral frontostriatal activation from PRE to POST3 during retrieval, regardless of education. Activation changes from PRE to POST3 varied as a function of education in 2 regions of the right temporal lobe: participants with lower education showed increased activation, while those with higher education showed decreased activation. These regions were initially less active in people with lower education. Results suggest a strategic shift in people with lower education and expertise building in those with higher education, along with a restoration of initial education-related differences.

Normative data for the story recall subtest of the BEM-144 in the Quebec-French population aged 50 years and over.

OBJECTIVE: The story recall subtest of the Batterie d'Efficience Mnésique (BEM-144) is a verbal episodic memory test that assesses immediate and episodic memory. Variables such as age, sex, and education level can impact performance on this type of memory test, as can cultural differences. Therefore, the purpose of this study was to establish normative data for the story recall subtest of the BEM-144 in the elderly French-Quebec population. METHOD: The normative sample consisted of 260 healthy individuals aged 50-90 years, all from the province of Quebec, Canada. Analyses were performed to estimate the association between age, sex, and education level on one hand, and immediate and delayed recall performance, on the other hand. RESULTS: The results show that all sociodemographic variables are significantly associated with story recall performance. Normative data are proposed in the form of regression equations. CONCLUSIONS: Overall, these norms will be beneficial for the evaluation and detection of episodic memory impairment in middle-aged and older adults.

Putting music to trial: Consensus on key methodological challenges investigating music-based rehabilitation.

Major advances in music neuroscience have fueled a growing interest in music-based neurological rehabilitation among researchers and clinicians. Musical activities are excellently suited to be adapted for clinical practice because of their multisensory nature, their demands on cognitive, language, and motor functions, and music's ability to induce emotions and regulate mood. However, the overall quality of music-based rehabilitation research remains low to moderate for most populations and outcomes. In this consensus article, expert panelists who participated in the Neuroscience and Music VII conference in June 2021 address methodological challenges relevant to music-based rehabilitation research. The article aims to provide guidance on challenges related to treatment, outcomes, research designs, and implementation in music-based rehabilitation research. The article addresses how to define music-based rehabilitation, select appropriate control interventions and outcomes, incorporate technology, and consider individual differences, among other challenges. The article highlights the value of the framework for the development and evaluation of complex interventions for music-based rehabilitation research and the need for stronger methodological rigor to allow the widespread implementation of music-based rehabilitation into regular clinical practice.

Sex differences in patterns of associative memory-related activation in individuals at risk of Alzheimer's disease.

The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how relationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in understanding the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.

Multidomain trials to prevent dementia: addressing methodological challenges.

BACKGROUND: Multidomain trials to prevent dementia by simultaneously targeting multiple risk factors with non-pharmacological lifestyle interventions show promise. Designing trials to evaluate the efficacy of individual interventions and their combinations is methodologically challenging. Determining the efficacy is, nevertheless, important to individuals, payers, and for resource allocations to support intervention implementation. MAIN BODY: The central rationale for seminal trials improving cardiovascular health or reducing falls risk in older adults is that multifactorial conditions may be amenable to improvement by simultaneously targeting multiple modifiable risk factors. Similar reasoning underlies lifestyle interventions to reduce dementia risk using combinations of physical exercise, cognitive training, diet, amelioration of vascular-metabolic risk factors, and improving sleep quality. Randomizing individuals with at least two modifiable risk factors to "standardly tailored" interventions to mitigate their risk factors, versus a comparator arm, will yield an unbiased estimate of the cumulative average effect of modifying more versus fewer risk factors. The between-group difference in the cognitive primary outcome will reflect both the main effects of the mitigated risk factors, as well as their synergistic effects. However, given the positive trial results, there are inherent challenges in quantifying post hoc which components, or combination of components, were responsible for improvements in cognition. Here, we elaborate on these methodological challenges and important considerations in using a standardly tailored design with two arms (one consisting of multidomain interventions tailored to participants' risk profiles and another consisting of active control conditions). We compare this approach to fully factorial designs and highlight the disadvantages and advantages of each. We discuss partial solutions, including analytical strategies such as risk reduction scores that measure reductions in the number or severity of risk factors in each study arm. Positive results can support the causal inference that between-group differences in the primary cognitive outcome were due to risk factor modification. CONCLUSION: Standardly tailored designs are pragmatic and feasible evaluations of multidomain interventions to reduce dementia risk. We propose sensitivity and exploratory analyses of between-group reductions in the severity of risk factors, as a methodology to bolster causal inferences that between-group differences in the primary cognitive outcome are due to the risk factors modified.

Mechanisms of processing speed training and transfer effects across the adult lifespan: protocol of a multi-site cognitive training study.

BACKGROUND: In recent years, cognitive training has gained popularity as a cost-effective and accessible intervention aiming at compensating for or even counteracting age-related cognitive declines during adulthood. Whereas the evidence for the effectiveness of cognitive training in general is inconsistent, processing speed training has been a notable successful exception, showing promising generalized benefits in untrained tasks and everyday cognitive functioning. The goal of this study is to investigate why and when processing speed training can lead to transfer across the adult lifespan. Specifically, we will test (1) whether training-induced changes in the rate of evidence accumulation underpin transfer to cognitive performance in untrained contexts, and (2) whether these transfer effects increase with stronger attentional control demands of the training tasks. METHODS: We will employ a multi-site, longitudinal, double-blinded and actively controlled study design with a target sample size of N = 400 adult participants between 18 and 85 years old. Participants will be randomly assigned to one of three processing speed training interventions with varying attentional control demands (choice reaction time, switching, or dual tasks) which will be compared to an active control group training simple reaction time tasks with minimal attentional control demands. All groups will complete 10 home-based training sessions comprising three tasks. Training gains, near transfer to the untrained tasks of the other groups, and far transfer to working memory, inhibitory control, reasoning, and everyday cognitive functioning will be assessed in the laboratory directly before, immediately after, and three months after training (i.e., pretest, posttest, and follow-up, respectively). We will estimate the rate of evidence accumulation (drift rate) with diffusion modeling and conduct latent-change score modeling for hypothesis testing. DISCUSSION: This study will contribute to identifying the cognitive processes that change when training speeded tasks with varying attentional control demands across the adult lifespan. A better understanding of how processing speed training affects specific cognitive mechanisms will enable researchers to maximize the effectiveness of cognitive training in producing broad transfer to psychologically meaningful everyday life outcomes. Trial registration Open Science Framework Registries, registration https://doi.org/10.17605/OSF.IO/J5G7E ; date of registration: 9 May 2022.

Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex.

BACKGROUND: Omega-3 (n-3) PUFAs are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodologic issues, including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier. OBJECTIVES: This study evaluated the association between serum n-3 PUFAs and performance across 4 cognitive domains, overall and by sex, while controlling for other LCFAs. METHODS: In total, 386 healthy older adults (aged 77.4 ± 3.8 y; 53% females) from the Quebec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and nonverbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs. RESULTS: Higher n-3 PUFA concentrations were associated with better nonverbal memory and processing speed in fully adjusted models not including other LCFAs (ßs of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (ßs of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (ßs of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of EPA, whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and nonverbal episodic memory in females and with better executive functioning and processing speed in males. CONCLUSIONS: These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.