Impaired perceptual discrimination of complex objects in older adults at risk for dementia.

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into "at-risk" (score <26; n = 15) and "healthy" (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at-risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD.

Aging Enhances Neural Activity in Auditory, Visual, and Somatosensory Cortices: The Common Cause Revisited.

In humans, age-related declines in vision, hearing, and touch coincide with changes in amplitude and latency of sensory-evoked potentials. These age-related differences in neural activity may be related to a common deterioration of supra-modal brain areas (e.g., PFC) that mediate activity in sensory cortices or reflect specific sensorineural impairments that may differ between sensory modalities. To distinguish between these two possibilities, we measured neuroelectric brain activity while 37 young adults (18-30 years, 18 males) and 35 older adults (60-88 years, 20 males) were presented with a rapid randomized sequence of lateralized auditory, visual, and somatosensory stimuli. Within each sensory domain, we compared amplitudes and latencies of sensory-evoked responses, source activity, and functional connectivity (via phase-locking value) between groups. We found that older adults' early sensory-evoked responses were greater in amplitude than those of young adults in all three modalities, which coincided with enhanced source activity in auditory, visual, and somatosensory cortices. Older adults also showed stronger neural synchrony than young adults between superior prefrontal and sensory cortices; and in older adults, the degree of phase synchrony was positively correlated with the magnitude of source activity in sensory areas. Critically, older adults who showed enhanced neural activity in one sensory domain also showed enhanced activity in other modalities. Together, these findings support the common cause hypothesis of aging and highlight the role of prefrontal regions in exerting top-down control over sensory cortices.SIGNIFICANCE STATEMENT A prominent theory of aging posits that age-related declines in sensory processing across domains are related to a single common neurobiological mechanism. However, the neural evidence supporting this common cause hypothesis has remained elusive. Our study revealed robust age-related changes in three sensory domains across a range of neural metrics. Importantly, older adults who showed increased neural activity within one sensory domain also showed enhanced neural activity in the other two sensory modalities. No such relation among activity in sensory cortices was observed in young adults. Age-related increases in neural activity in sensory cortices coincided with enhanced neural synchrony between the PFC and sensory cortices, underlining the importance of the PFC in regulating sensory processing.

The potential roles of excitatory-inhibitory imbalances and the repressor element-1 silencing transcription factor in aging and aging-associated diseases.

Disruptions to the central excitatory-inhibitory (E/I) balance are thought to be related to aging and underlie a host of neural pathologies, including Alzheimer's disease. Aging may induce an increase in excitatory signaling, causing an E/I imbalance, which has been linked to shorter lifespans in mice, flies, and worms. In humans, extended longevity correlates to greater repression of genes involved in excitatory neurotransmission. The repressor element-1 silencing transcription factor (REST) is a master regulator in neural cells and is believed to be upregulated with senescent stimuli, whereupon it counters hyperexcitability, insulin/insulin-like signaling pathway activity, oxidative stress, and neurodegeneration. This review examines the putative mechanisms that distort the E/I balance with aging and neurodegeneration, and the putative roles of REST in maintaining neuronal homeostasis.

Household physical activity is positively associated with gray matter volume in older adults.

BACKGROUND: Total physical activity is positively associated with brain volume and cognition in older adults. While we have ample evidence that recreational physical activity influences brain health, the contributions of other daily activities are less understood. In particular, the associations between household physical activity and brain health in older adults is underexplored. The purpose of this study was to identify associations between household physical activity, brain volume, and cognition in a sample of cognitively unimpaired older adults. METHODS: We report data from 66 cognitively unimpaired older adults (71 ± 4 years) who participated in a health evaluation, cognitive assessment, and structural brain imaging. Physical activity was assessed using the Phone-FITT questionnaire and separated into household and recreational physical activity. We quantified whole brain volume, gray matter volume, and white matter volume, and assessed cognitive performance in four domains: memory, working memory/attention, processing speed, and executive function. Associations between physical activity, brain volume, and cognition were investigated in an omnibus approach using two multivariate analysis of variance (MANOVA) models. The first model assessed the associations between physical activity and brain volume adjusting for age, sex, Framingham Risk score (FRS) and intracranial volume. The second model assessed the associations between physical activity and overall cognitive performance adjusting for age, sex, FRS and education. Post hoc regression analyses were conducted to investigate significant MANOVA results. We also conducted further regression analyses to investigate associations with hippocampal and frontal lobe volume. RESULTS: Household, but not recreational, physical activity was positively associated with brain volume measurements (F = 3.07, p = .035), specifically gray matter volume (t = 2.51, p = .015). Further exploratory analyses identified that household physical activity was associated with hippocampal (p = .015) and frontal lobe (p = .010) volume. No significant relationships were observed between household or recreational physical activity and cognition. CONCLUSION: Time spent engaging in household physical activity was positively associated with brain volume, specifically gray matter volume, in older adults. Highlighting the benefits associated with household chores may motivate older adults to be more active by providing a more attainable, low risk form of physical activity.

Inhibitory Control Deficits in Individuals with Amnestic Mild Cognitive Impairment: a Meta-Analysis.

Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer's disease that is characterized by impairments in episodic memory. Recent evidence has shown that inhibitory control is also impaired in aMCI. The aim of the present meta-analysis was to quantify inhibitory control ability in individuals with aMCI by examining performance across a range of well-defined inhibition paradigms that tapped into one of three inhibitory control subtypes (i) interference control (e.g., Stroop task), (ii) response inhibition (e.g., Go/Nogo task), or (iii) inhibition of cognitive sets (Wisconsin Card Sort Task). Reference databases (PsychINFO, PubMed, and Web of Science) were searched for studies comparing individuals with aMCI to healthy controls on behavioural measures of inhibition. Across 70 effect sizes involving 2184 adults with aMCI and 3049 controls, overall inhibition deficits of moderate magnitude (g = -0.73) were found among individuals with aMCI. Inhibition deficits were moderate in size regardless of inhibitory control subtype: interference control (g = -0.74), response inhibition (g = -0.71), inhibition of cognitive sets (g = -0.76). Subgroup analyses revealed that Stroop outcome measure (reaction time vs. accuracy) and recruitment source (clinical vs. community) moderated interference control deficits. Together these findings support a generalized inhibition deficit in aMCI, and suggest that inhibition tasks should be included routinely in neuropsychological test batteries to provide a more comprehensive overview of executive dysfunction in aMCI.

Sex differences in the relationship between dietary pattern adherence and cognitive function among older adults: findings from the NuAge study.

BACKGROUND: Consumption of a prudent dietary pattern rich in healthy nutrients is associated with enhanced cognitive performance in older adulthood, while a Western dietary pattern low in healthy nutrients is associated with poor age-related cognitive function. Sex differences exist in dietary intake among older adults; however, there is a paucity of research examining the relationship between sex-specific dietary patterns and cognitive function in later life. METHODS: The current study aimed to investigate sex differences in the relationship between sex-specific dietary pattern adherence and global cognitive function at baseline and over a 3-year follow-up in 1268 community-dwelling older adults (Mage = 74 years, n = 664 women, n = 612 men) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). A 78-item Food Frequency Questionnaire was used to estimate dietary intake over the previous year. Sex-specific dietary pattern scores were derived using principal component analysis. Global cognition was assessed using the Modified Mini-Mental State Examination (3MS). RESULTS: Adjusted linear mixed effects models indicated that a healthy, prudent dietary pattern was not associated with baseline cognitive performance in men or women. No relationship was found between Western dietary pattern adherence and baseline cognitive function in women. Among men, adherence to an unhealthy, Western dietary pattern was associated with poorer baseline cognitive function (ß = - 0.652, p = 0.02, 95% CI [- 1.22, - 0.65]). No association was found between prudent or Western dietary patterns and cognitive change over time in men or women. CONCLUSIONS: These findings highlight the importance of conducting sex-based analyses in aging research and suggest that the relationship between dietary pattern adherence and cognitive function in late life may be sex-dependent.

Cardiovascular risk and encoding-related hippocampal connectivity in older adults.

BACKGROUND: Cardiovascular conditions contribute to brain volume loss, reduced cerebrovascular health, and increased dementia risk in aging adults. Altered hippocampal connectivity has also been observed in individuals with cardiovascular conditions, yet the functional consequences of these changes remain unclear. In the present study, we collected functional magnetic resonance imaging data during memory encoding and used a psychophysiological interaction analysis to examine whether cardiovascular burden, indexed using the Framingham risk score, was associated with encoding-related hippocampal connectivity and task performance in cognitively-intact older adults between 65 and 85 years of age. Our goal was to better understand the early functional consequences of vascular and metabolic dysfunction in those at risk for cognitive decline. RESULTS: High Framingham risk scores were associated with lower total brain volumes. In addition, those with high Framingham risk scores showed an altered relationship between left hippocampal-medial prefrontal coupling and task performance compared to those with low Framingham risk scores. Specifically, we found a significant interaction of Framingham risk and learning on connectivity between the left hippocampus and primarily left midline prefrontal regions comprising the left ventral anterior cingulate cortex and medial prefrontal cortex. Those with lower Framingham risk scores showed a pattern of weaker connectivity between left hippocampal and medial prefrontal regions associated with better task performance. Those with higher Framingham risk scores showed the opposite pattern; stronger connectivity was associated with better performance. CONCLUSIONS: Findings from the current study show that amongst older adults with cardiovascular conditions, higher Framingham risk is associated with lower brain volume and altered left hippocampal-medial prefrontal coupling during task performance compared to those with lower Framingham risk scores. This may reflect a compensatory mechanism in support of memory function and suggests that older adults with elevated cardiovascular risk are vulnerable to early Alzheimer disease-like dysfunction within the episodic memory system.

State of the science on mild cognitive impairment (MCI).

Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects 10-15% of the population over the age of 65. The failure of drug trials in Alzheimer's disease (AD) treatment has shifted researchers' focus toward delaying progression from MCI to dementia, which would reduce the prevalence and costs of dementia profoundly. Diagnostic criteria for MCI increasingly emphasize the need for positive biomarkers to detect preclinical AD. The phenomenology of MCI comprises lower quality-of-life, greater symptoms of depression, and avoidant coping strategies including withdrawal from social engagement. Neurobiological features of MCI are hypoperfusion and hypometabolism in temporoparietal cortices, medial temporal lobe atrophy particularly in rhinal cortices, elevated tau and phosphorylated tau and decreased Aß42 in cerebrospinal fluid, and brain Aß42 deposition. Elevated tau can be identified in MCI, particularly in the entorhinal cortex, using positron emission tomography, and analysis of signal complexity using electroencephalography or magnetoencephalography holds promise as a biomarker. Assessment of MCI also relies on cognitive screening and neuropsychological assessment, but there is an urgent need for standardized cognitive tests to capitalize on recent discoveries in cognitive neuroscience that may lead to more sensitive measures of MCI. Cholinesterase inhibitors are frequently prescribed for MCI, despite the lack of evidence for their efficacy. Exercise and diet interventions hold promise for increasing reserve in MCI, and group psychoeducational programs teaching practical memory strategies appear effective. More work is needed to better understand the phenomenology and neurobiology of MCI, and how best to assess it and delay progression to dementia.

Effects of Question Framing on Self-Reported Memory Concerns across the Lifespan.

Background/Study Context: Evidence regarding whether there is an age-related increase in subjective memory concerns is mixed. The goal of this study was to investigate whether calling to mind specific instances of memory failures affects the likelihood that individuals report being concerned about their memory. METHODS: Young, middle-aged, and older individuals responded to statements that probed general memory concerns (e.g., I am concerned about my memory) before or after probing the frequency of memory difficulties in specific everyday situations (e.g., I forget appointments). RESULTS: We found no relationship between age and memory concern, and older compared to younger adults reported having fewer everyday memory failures. Furthermore, individuals of all ages were more likely to report being concerned about their memory if asked before relative to after rating the frequency of specific everyday memory failures. CONCLUSION: Increasing age is associated with fewer reported difficulties with specific everyday memory situations, but people of all ages display anchoring effects on memory concern based on realistic occurrences of remembering. Our findings have implications for the measurement of self-reported memory as they show that the order of questions can influence responding.

Effect of conceptual and lexical errorless versus trial-and-error learning in amnestic mild cognitive impairment.

Errorless learning (EL), involving presenting the target information during encoding, is generally considered effective for teaching information to memory-impaired populations. However, evidence suggests that trial-and-error learning (TEL) can benefit healthy older adults' memory when guesses are conceptually related to the target. To determine whether TEL can benefit persons with mild cognitive impairment (aMCI), 24 participants with aMCI were given cues associated with nine target words. Half the sample received Conceptual cues (e.g., "beverage") and the other half received Lexical cues (e.g., SC_______). All underwent an EL study phase, in which the target was presented immediately after the cue, and a TEL phase, in which they made guesses from the cue before the target was presented. Cued recall was tested immediately and 24 h later. At immediate but not 24-h delayed recall, EL targets were better remembered than TEL targets in both conditions. Verbal memory performance appeared to explain why certain individuals benefited more from EL relative to TEL, while semantic memory performance appeared to explain why some people benefited more from conceptual than lexical errors. Thus, EL-based memory intervention for aMCI is likely to be more effective than TEL, particularly to the extent that semantic or episodic memory is affected.

Response Time Consistency Is an Indicator of Executive Control Rather than Global Cognitive Ability.

OBJECTIVES: Intraindividual variability increases with age, but the relative strength of association with cognitive domains is still unclear. The objective of this study was to examine the relation between cognitive domains and the shape and spread of response time (RT) distributions as indexed by intraindividual standard deviation (ISD), and ex-Gaussian parameters (µ, σ, τ). METHODS: Healthy adults (40 young [aged 18-30 years], 40 young-old [aged 65-74 years], and 41 old-old [aged 75-85 years]) completed neuropsychological testing and a touch-screen attention task from which ISD and ex-Gaussian parameters were derived. The relation between RT performance and cognitive domains (memory, processing speed, executive functioning) was examined with structural equation modeling (SEM), and the predictive power of RT distribution indices over age was investigated with linear regression. RESULTS: ISD, µ, and τ, but not σ, showed a linear increase with age group. An SEM showed that independent of age, τ was most strongly associated with executive functioning, while µ exhibited less critical associations. Linear regression indicated that µ and τ explained a significant portion of variance in processing speed and executive ability in addition to age group. Memory was more parsimoniously predicted by age, without any significant contribution of ex-Gaussian parameters. CONCLUSIONS: The findings suggest that exceptionally slow responses convey attention lapses through wavering of cognitive control, which strongly correspond to executive functioning tests. General slowing and extremely slow responses predicted processing speed and executive performance beyond age group, indicating that RT metrics are sensitive to differences in cognitive ability. (JINS, 2018, 24, 456-465).

Learning from your mistakes: does it matter if you're out in left foot, I mean field?

Studies have shown that generating errors prior to studying information (pencil-?) can improve target retention relative to passive (i.e., errorless) study, provided that cues and targets are semantically related (pencil-ink) and not unrelated (pencil-frog). In two experiments, we manipulated semantic proximity of errors to targets during trial-and-error to examine whether it would modulate this error generation benefit. In Experiment 1, participants were shown a cue (band-?) and asked to generate a related word (e.g., drum). Critically, they were given a target that either matched the semantic meaning of their guess (guitar) or mismatched it (rubber). In Experiment 2, participants studied Spanish words where the English translation either matched their expectations (pariente-relative) or mismatched it (carpeta-folder). Both experiments show that errors benefit memory to the extent that they overlap semantically with targets. Results are discussed in terms of the retrieval benefits of activating related concepts during learning.

The benefits of errorless learning for people with amnestic mild cognitive impairment.

The aim of this study was to explore whether errorless learning leads to better outcomes than errorful learning in people with amnestic mild cognitive impairment (MCI), and to examine whether accuracy in error recognition relates to any observed benefit of errorless over errorful learning. Nineteen participants with a clinical diagnosis of amnestic MCI were recruited. A word-list learning task was used and learning was assessed by free recall, cued recall and recognition tasks. Errorless learning was significantly superior to errorful learning for both free recall and cued recall. The benefits of errorless learning were less marked in participants with better error recognition ability. Errorless learning methods are likely to prove more effective than errorful methods for those people with MCI whose ability to monitor and detect their own errors is impaired.

Cognitive Contributors to Multiple Errands Test (MET) Performance.

OBJECTIVE: The Multiple Errands Test (MET) was designed to measure the effect of executive dysfunction on everyday life activities, but little is known about the cognitive requirements for successful performance. This study's objective was to investigate cognitive functions associated with successful MET performance, specifically, the Baycrest-MET. METHOD: Correlation analysis examined relationships between Baycrest-MET performance and neuropsychological functioning in participants with acquired brain injury (ABI; N = 27). RESULTS: The association of tasks omitted with executive function (EF) accounted for 15.2%-42.3% of the variance; the association of tasks omitted with attention and processing speed, for 16.8%-24.0%; and the association of tasks omitted and total rule breaks with visuospatial memory, for 18.5%-31.4%. CONCLUSION: Poor performance on the Baycrest-MET in people with ABI is associated with impairments of EF, attention, memory, and processing speed. Different patterns of performance may arise from different constellations of impairments.

Negative Emotional Verbal Memory Biases in Mild Cognitive Impairment and Late-Onset Depression.

OBJECTIVE: Early and preferential targeting of limbic structures by Alzheimer disease (AD)-related pathology suggests emotion dysregulation may serve as a marker of AD risk. We studied emotional verbal memory in two groups at risk for AD, amnestic mild cognitive impairment (aMCI) and late-onset depression (LOD), to test the hypothesis that aMCI and LOD would be characterized by a negative bias in emotional memory, whereas cognitively normal (CN) adults would show the "positivity effect" associated with healthy aging. METHODS: Participants completed a novel test of emotional verbal memory, the Emotional Verbal Learning Test (EVeLT), consisting of a 15-item list of words with positive, negative, or neutral valence. Recall as a function of group and valence was analyzed using mixed analysis of variance. Spearman's rho was used to examine associations between EVeLT, mood, and executive function. MCI and CN participants had no current or past history of mood or anxiety disorders. aMCI participants met neuropsychological criteria for single-domain aMCI (sd-aMCI). LOD developed their first episode of depression at ≥60 years of age. RESULTS: CN adults recalled more positive words, whereas sd-aMCI and LOD adults recalled more negative, relative to neutral, words on the EVeLT. Positive emotional memory and negative attitudes regarding self were inversely correlated in CN adults. CONCLUSION: sd-aMCI and LOD groups show negative emotional memory biases, consistent with our hypothesis that emotion dysregulation is a signature of AD risk.

Clinicians' perceptions of the clinical utility of the Multiple Errands Test for adults with neurological conditions.

This study examined the clinical utility of the Multiple Errands Test (MET) from the perspective of clinicians. Employing a qualitative descriptive design, in-depth semi-structured interviews were conducted with eight occupational therapists. Participants had an average of 12 years clinical experience and their experience using the MET varied. Interviews were transcribed and analysed using framework analysis. Three dominant themes emerged from the data. Theme 1 was that clinicians value the MET because it reflects real-life functioning. Clinicians perceived the MET to be a unique assessment collecting data on functional performance, and sensitive to higher level cognitive deficits. Theme 2 was that the MET could be used flexibly depending on one's rehabilitation goals. Clinicians employed the MET as an assessment to inform the direction of treatment and as a component of their intervention. Theme 3 was that the MET is a challenging assessment requiring buy in and commitment from therapists. This study is the first to report clinicians' perspectives of the clinical utility of the MET. It reinforces the importance of ecologically valid tests, and augments existing research evaluating psychometric properties of the MET by describing how the MET has been employed in rehabilitation settings to improve health outcomes for adults with neurological conditions.

Reliability and construct validity of a revised Baycrest Multiple Errands Test.

Surprisingly few ecologically-valid assessments of executive function exist, but the Baycrest Multiple Errands Test (BMET) shows promise in identifying executive impairment. The goal of the present study was to develop both a revised version of the assessment (BMET-R), to improve the test's ability to discriminate between patients and healthy participants, and an alternate form of the BMET-R to permit repeat testing. Sixteen individuals with acquired brain injury (ABI) due to stroke or trauma and 16 healthy participants completed a series of neuropsychological assessments, questionnaires, the BMET-R and its alternate form (in counterbalanced order). The results of the study indicated that participants with ABI omitted more tasks, broke more rules, and were less efficient than healthy participants on both the revised BMET-R and its alternate form. Moreover, significant correlations were found between the two versions of the BMET-R for task completions, omissions, errors, rule breaks and inefficiencies but few significant correlations were observed between the BMET-R versions and measures of executive dysfunction in everyday life. These results indicate that the two versions of the BMET-R are able to dissociate the performance of participants with ABI from that of healthy participants. However, despite overlaps in performance and correlations between the two versions of the BMET-R, they did not identically assess executive deficits. This suggests that caution should be used when constructing and validating alternate versions of performance-based assessments.

Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network.

PURPOSE: White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH. MATERIALS AND METHODS: Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation. RESULTS: VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2 = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2) = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs. CONCLUSION: In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation.

Nutrition risk and cognitive performance in community-living older adults without cognitive impairment: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

Malnutrition is correlated with poor cognition; however, an understanding of the association between nutrition risk, which precedes malnutrition, and cognition is lacking. This study aimed to determine if nutrition risk measured with the SCREEN-8 tool is associated with cognitive performance among cognitively healthy adults aged 55+, after adjusting for demographic and lifestyle covariates. Sex- and age-stratified analyses were also explored. Baseline data from the Canadian Longitudinal Study on Aging was used. Cognition was determined using a 6-measure composite score based on four executive functions and two memory tasks, taking into account age, sex, and education. Multivariable linear regression was performed while adjusting for body mass index (BMI), lifestyle, and health covariates in the entire sample (n = 11 378) and then stratified by sex and age. Approximately half of participants were female (54.5%) aged 65+ (54.1%). Greater nutrition risk was associated with poorer cognitive performance in the entire sample (F[1, 11 368] = 5.36, p = 0.021) and among participants aged 55-64 (n = 5227; F[1, 5217] = 5.45, p = 0.020). Sex differences in lifestyle and health factors associated with cognition were apparent, but nutrition risk was not associated with cognition in sex-stratified models. Based on this analysis, there may be an association between nutrition risk and cognitive performance in older adults. When screening for either cognitive impairment or nutrition risk, complementary assessments for these conditions is warranted, as early intervention may provide benefit.

The Role of the Gut Microbiome in Diet and Exercise Effects on Cognition: A Review of the Intervention Literature.

Interest in the gut-brain axis and its implications for neurodegenerative diseases, such as Alzheimer's disease and related dementias, is growing. Microbial imbalances in the gastrointestinal tract, which are associated with impaired cognition, may represent a therapeutic target for lowering dementia risk. Multicomponent lifestyle interventions are a promising dementia risk reduction strategy and most often include diet and exercise, behaviors that are also known to modulate the gut microbiome. A better understanding of the role of the gut microbiome in diet and exercise effects on cognition may help to optimize these lifestyle interventions. The purpose of this review is to summarize findings from diet and exercise interventions that have investigated cognitive changes via effects on the microbiome. We aim to discuss the underlying mechanisms, highlight current gaps in the field, and provide new research directions. There is evidence mainly from rodent studies supporting the notion that microbiota changes mediate the effects of diet and exercise on cognition, with potential mechanisms including end-product metabolites and regulation of local and systemic inflammation. The field lacks whole diet and exercise interventions, especially those involving human participants. It is further limited by heterogeneous rodent models, outcome assessments, and the absence of proper mediation analyses. Trials including older adults with dementia risk factors, factorial designs of diet and exercise, and pre and post measures of microbiota, end-product metabolites, and inflammation would help to elucidate and potentially leverage the role of the microbiome in lowering dementia risk through lifestyle modification.