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.

Effect of High-Intensity Interval Training and Moderate-Intensity Continuous Training in People With Poststroke Gait Dysfunction: A Randomized Clinical Trial.

Background The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness (V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$) and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ and 6-minute walk distance (6MWD). Methods and Results In this 24-week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work-to-recovery protocols: 30:60 and 120:180 seconds. V̇O2 and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ and 6MWD. Assessors were blinded to the treatment group for V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait-economy, 10-meter gait-velocity, balance, stair-climb performance, strength, and quality-of-life. Among 47 participants randomized to either MICT (n=23) or HIIT (n=24) (mean age, 62±11 years; 81% men), 96% completed training. In intention-to-treat analysis, change in V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ for MICT versus HIIT was 2.4±2.7 versus 5.7±3.1 mL·kg-1·min-1 (mean difference, 3.2 [95% CI, 1.5-4.8]; P<0.001), and change in 6MWD was 70.9±44.3 versus 83.4±53.6 m (mean difference, 12.5 [95% CI, -17 to 42]; P=0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference, 2.07 mL·kg-1·min-1 [95% CI, 0.59-3.6]; P=0.008). No other between-group differences were observed. During V̇O2 monitoring at 8 and 24 weeks, MICT reached 84±14% to 87±18% of V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ while HIIT reached 101±22% to 112±14% of V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ (during peak bouts). Conclusions HIIT resulted in more than a 2-fold greater and clinically important change in V̇O2peak$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{peak}} $$ than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in ~3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03006731.

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.

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.

Effect of sex on the APOE4-aging interaction in the white matter microstructure of cognitively normal older adults using diffusion-tensor MRI with orthogonal-tensor decomposition (DT-DOME).

The influence of the apolipoprotein E ε4 allele (APOE4) on brain microstructure of cognitively normal older adults remains incompletely understood, in part due to heterogeneity within study populations. In this study, we examined white-matter microstructural integrity in cognitively normal older adults as a function of APOE4 carrier status using conventional diffusion-tensor imaging (DTI) and the novel orthogonal-tensor decomposition (DT-DOME), accounting for the effects of age and sex. Age associations with white-matter microstructure did not significantly depend on APOE4 status, but did differ between sexes, emphasizing the importance of accounting for sex differences in APOE research. Moreover, we found the DT-DOME to be more sensitive than conventional DTI metrics to such age-related and sex effects, especially in crossing WM fiber regions, and suggest their use in further investigation of white matter microstructure across the life span in health and disease.

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.

Strategy-training post-stroke via tele-rehabilitation: a pilot randomized controlled trial.

PURPOSE: Long-term limitations in social participation are common after stroke. Whether these can be attenuated through a tele-rehabilitation approach is unknown. We were particularly interested in examining transfer of learning effects which could result in broader improvements in social participation. METHODS: We adapted a strategy training rehabilitation approach (tele-CO-OP) for remote delivery. Participants with chronic stroke were randomized to receive the intervention (EXPT) or to a wait list (Control). Feasibility and acceptability were measured via attendance scores, satisfaction with the training and therapist evaluation of engagement with the training. The primary outcome measure was the Canadian Occupational Performance Measure (COPM), a standardized semi-structured interview which elicits difficulties in day-to-day life. RESULTS: Seventeen participants were randomized. Tele-CO-OP was found to be feasible and acceptable: participants reported high satisfaction and engagement, and missed few sessions. Large effect sizes for transfer of learning effects were observed in favor of receiving tele-CO-OP vs being waitlisted. Significant benefits were also conferred to the Control group following receipt of tele-CO-OP. The intervention also appeared to improve mood. CONCLUSIONS: This exploratory study demonstrates the feasibility and acceptability of tele-CO-OP and provides preliminary evidence for transfer of learning effects to untrained everyday social participation activities. Trial registration number: NCT02724813.

Stroke results in long-term limitations in social participation.The Cognitive Orientation to daily Occupational Performance (CO-OP) Approach provides a potential avenue for ameliorating these limitations.This pilot randomized controlled trial demonstrated that it is feasible to deliver tele-CO-OP and that positive benefits may accrue to those receiving the intervention for both trained and untrained activities.Tele-CO-OP is a promising intervention for addressing long-term participation limitations in individuals with chronic stroke.

Time of Day Effects on Inhibitory Functioning: Cognitive and Neural Evidence of Sundowning in Amnestic Mild Cognitive Impairment.

BACKGROUND: Amnestic mild cognitive impairment (aMCI), a prodromal phase of Alzheimer's disease (AD), is characterized by episodic memory dysfunction, but inhibitory deficits have also been commonly reported. Time of day (TOD) effects have been confirmed in 1) healthy aging on cognitive processes such as inhibitory control, and 2) on behavior in AD (termed the sundowning effect), but no such research has addressed aMCI. OBJECTIVE: The present study examined the impact of TOD on the behavioral and electrophysiological correlates of inhibition in 54 individuals with aMCI and 52 healthy controls (HCs), all of morning chronotype. METHODS: Participants were randomly assigned to complete two inhibition tasks (Go-NoGo and Flanker) during their optimal (morning) or non-optimal (evening) TOD, while electroencephalography was recorded. RESULTS: Both tasks elicited changes in N2 and P3 event-related potential (ERP) components, which commonly index inhibitory functioning. Analyses showed that the Go-NoGo difference in P3 amplitude was reduced in individuals with aMCI relative to HCs. Compared to HCs, the Flanker difference in P3 amplitude was also reduced and coincided with more errors in the aMCI group. Notably, these behavioral and ERP differences were exaggerated in the non-optimal TOD relative to the optimal TOD. CONCLUSION: Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI.

The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan.

Background: Reversible lifestyle behaviors (modifiable risk factors) can reduce dementia risk by 40%, but their prevalence and association with cognition throughout the adult lifespan is less well understood. Methods: The associations between the number of modifiable risk factors for dementia (low education, hypertension, hearing loss, traumatic brain injury, alcohol or substance abuse, diabetes, smoking, and depression) and cognition were examined in an online sample (N = 22,117, ages 18-89). Findings: Older adults (ages 66-89) had more risk factors than middle-aged (ages 45-65) and younger adults (ages 18-44). Polynomial regression revealed that each additional risk factor was associated with lower cognitive performance (equivalent to 3 years of aging), with a larger association as age increased. People with no risk factors in their forties to seventies showed similar cognitive performance to people 10 or 20 years younger with many risk factors. Interpretation: Modifiable dementia risk factors amplify lifespan age differences in cognitive performance.

Familiarity Deficits for Words and Objects in Amnestic Mild Cognitive Impairment in a Context Minimizing the Role of Recollection.

OBJECTIVES: Amnestic mild cognitive impairment (aMCI) is associated with cortical thinning in perirhinal and entorhinal cortices, key regions of the brain supporting familiarity. Individuals with aMCI demonstrate familiarity deficits in their behavior, often repeating questions in the same conversation. While familiarity deficits in healthy aging are minimal, past studies measuring familiarity in aMCI have mixed results, perhaps due to the influence of recollection. We therefore used a paradigm that minimized the influence of recollection, and hypothesized that familiarity would be impaired in aMCI relative to age-matched controls, but not in healthy older adults relative to younger adults. We also hypothesized that familiarity deficits in aMCI would be greater for objects than words because the perirhinal cortex plays a significant role in visual discrimination. METHODS: A sample of 36 younger adults, 38 cognitively intact older adults, and 30 older adults with aMCI made absolute frequency judgments for words and objects seen a variable number of times in an incidental encoding task. Estimates of familiarity were derived from correlating participants' frequency judgments with the actual frequency of presentation. RESULTS: Familiarity was largely spared in healthy aging, with minor deficits in familiarity for words. Familiarity deficits were evident in aMCI comparably for words and objects. DISCUSSION: The present research underscores the need to study familiarity in contexts minimizing recollection, particularly when comparing groups with different levels of recollection, and adds to our understanding of the phenomenology of aMCI. Familiarity deficits may provide an early biomarker of dementia risk.

The Effects of Aging and Time of Day on Inhibitory Control: An Event-Related Potential Study.

Time of day (TOD) influences on executive functions have been widely reported, with greater efficiency demonstrated at optimal relative to non-optimal TOD according to one's chronotype (i.e., synchrony effect). Older adults (OAs) show declines in inhibitory control and are more sensitive to the effects of circadian variation on executive functioning. To date, no studies have investigated the effects of TOD and aging on executive functioning using electrophysiological measures. The present study investigated the effects of aging and TOD on the neural correlates of inhibitory processing (N2 and P3) using event-related potentials (ERPs). Go-NoGo and Flanker tasks were administered to 52 OAs of morning chronotype and 51 younger adults (YAs) of afternoon-to-evening chronotype who were randomly assigned to morning or afternoon test sessions, with the optimal TOD for OAs in the morning and for YAs in the afternoon/evening. While behavioral results demonstrated no TOD effects, ERPs indicated synchrony effects. Both YAs and OAs showed greater modulation of Go-NoGo N2 and greater P3 amplitude during the non-optimal than optimal TOD, consistent with the synchrony effect. For the Flanker task, age differences in P3 amplitude were only apparent during the non-optimal TOD. These results suggest that processes associated with inhibitory control are differentially affected by TOD and aging, with age-related reductions in inhibitory efficiency during off-peak test times on measures of interference control. These findings highlight the sensitivity of ERPs to detect TOD effects in the absence of behavioral differences, confirm more pronounced TOD effects in OAs relative to YAs on ERP measures of interference control, and reinforce the need to assess and control for circadian typology in research studies.

Sex differences and modifiable dementia risk factors synergistically influence memory over the adult lifespan.

Introduction: More women than men develop Alzheimer's disease, yet women perform better and show less decline on episodic memory measures, a contradiction that may be accounted for by modifiable risk factors for dementia. Methods: Associations among age, sex, modifiable dementia risk factors, and cognition were measured in a cross-sectional online sample (n = 21,840, ages 18 to 89). Results: Across four tests of associative memory and executive functions, only a Face-Name Association task revealed sex differences in associative memory that varied by age. Men had worse memory than women (the equivalent of performing similar to someone 4 years older) across ages. Men had larger age differences than women (ie, worse memory in older ages) among people with no to one risk factor, but not those with multiple risk factors. Discussion: Because the relationship between dementia risk factors and age-related memory differences varies between men and women, sex-specific dementia prevention approaches are warranted.

Default Mode Network and Neural Phase Synchronization in Healthy Aging: A Resting State EEG Study.

Aging is associated with altered brain connectivity within the default mode network (DMN). Although research using functional magnetic resonance imaging has quantified age-related alterations in functional connectivity within this network during resting state, it is less clear how this may be reflected in electrophysiological measures, and how this relates to cognitive performance in older adults. The aim of this study was to quantify age differences in phase synchrony of the DMN during resting state, with particular focus on connectivity between the anterior node (i.e., medial prefrontal cortex, or mPFC) and other associated regions in this network. Electroencephalography was recorded from 55 younger adults (18-30 years, 28 females) and 34 older adults (64-88 years, 16 females) in two resting state conditions (eyes-open and -closed). Source-level functional connectivity was quantified using phase-locking value (PLV) with a spatial filter of six sources of interest, and were subjected to data-driven permutation testing between groups from 1 to 50 Hz. Older adults also completed tests of memory, language, executive functioning, and processing speed. Findings indicated decreased connectivity in the alpha2 range for older than younger adults between the mPFC and other DMN regions including the left angular gyrus and bilateral lateral temporal cortices, the latter of which were associated with lower performance in semantic fluency and executive functioning in older adults. Furthermore, greater PLV in theta and beta bands between the mPFC and posterior cingulate regions were found in older than younger adults. These results suggest age-related changes in DMN functional connectivity are non-uniform and frequency-dependent, and may reflect poorer performance in cognitive domains thought to decline with aging.

Occupational performance issues in older adults with subjective cognitive decline.

PURPOSE: To describe and categorize difficulties in daily activities of older adults with subjective cognitive decline (SCD) compared to individuals with mild cognitive impairment (MCI). METHODS: Deductive quantitative content analysis was used to classify reported issues in the performance of meaningful daily activities, in older adults with SCD (n = 67; age= 70 ± 6.3) or MCI (n = 42; age= 72 ± 6.6). The occupational performance issues were identified using the Canadian Occupational Performance Measure, a semi-structured interview, and categorised using the International Classification of Functioning, Disability and Health (ICF). RESULTS: Both groups identified issues in all nine ICF "Activities and Participation" domains, with no significant group effects on seven of them. The most frequently affected "Activities and Participation" domains in both groups were "Self-care" (e.g. exercise and diet); "Community, social and civic life" (e.g. social-leisure activities); and "General tasks and demands" (e.g. time management). Over 90% of the issues in both groups were described in the context of difficulties in "Mental functions" (e.g. memory and higher-level cognitive functions). CONCLUSIONS: Older adults with SCD, although independent, identified a variety of daily activities that they are not performing satisfactorily, remarkably similar in nature to the occupational performance issues described by older adults with MCI.Implications for RehabilitationOlder adults with SCD identified difficulties in performing social and leisure activities, maintaining healthy lifestyle behaviours, and managing multiple daily tasks.The daily challenges described by older adults with SCD are similar in nature to those identified by those with MCI.Older adults with SCD and MCI describe their daily challenges are related not only to memory problems, but also to executive dysfunction.Interventions for older adults with SCD should aim to improve self-identified problems in everyday functioning.

Reaction Time Intraindividual Variability Reveals Inhibitory Deficits in Single- and Multiple-Domain Amnestic Mild Cognitive Impairment.

OBJECTIVES: Amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease and other dementias, is characterized by episodic memory impairment. Recent evidence has shown inhibitory control deficits in aMCI, but the extent of these deficits across inhibitory domains (i.e., response inhibition and interference control) and aMCI subtypes (i.e., single vs multiple domain) remains unclear. Few studies have included reaction time intraindividual variability (RT IIV) in these efforts. The aim of this study was to compare response inhibition and interference control between aMCI subtypes using measures of accuracy, mean RT, and RT IIV. METHODS: We report data from 34 individuals with single-domain aMCI (sdaMCI, 66-86 years), 20 individuals with multiple-domain aMCI (mdaMCI, 68-88 years), and 52 healthy controls (HC, 64-88 years) who completed tasks of response inhibition (Go-NoGo) and interference control (Flanker). Group differences in accuracy, mean RT, and RT IIV were examined for both tasks. RESULTS: Individuals with mdaMCI had higher RT IIV than the other groups on both tasks. In RT IIV, we observed an interference control deficit in mdaMCI and sdaMCI relative to healthy controls, a finding not observed through accuracy or mean RT. DISCUSSION: RT IIV may detect subtle differences in inhibition deficits between aMCI subtypes that may not be evident with conventional behavioral measures. Findings support the supplementary use of RT IIV when assessing early executive function deficits.

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.

When I'm 64: Age-Related Variability in Over 40,000 Online Cognitive Test Takers.

OBJECTIVES: Age-related differences in cognition are typically assessed by comparing groups of older to younger participants, but little is known about the continuous trajectory of cognitive changes across age, or when a shift to older adulthood occurs. We examined the pattern of mean age differences and variability on episodic memory and executive function measures over the adult life span, in a more fine-grained way than past group or life-span comparisons. METHOD: We used a sample of over 40,000 people aged 18-90 who completed psychometrically validated online tests measuring episodic memory and executive functions (the Cogniciti Brain Health Assessment). RESULTS: Cognitive performance declined gradually over adulthood, and rapidly later in life on spatial working memory, processing speed, facilitation (but not interference), associative recognition, and set shifting. Both polynomial and segmented regression fit the data well, indicating a nonlinear pattern. Segmented regression revealed a shift from gradual to rapid decline that occurred in the early 60s. Variability between people (interindividual variability or diversity) and variability within a person across tasks (intraindividual variability or dispersion) also increased gradually until the 60s, and rapidly after. Confirmatory factor analysis revealed a single general factor (of variance shared between tasks) offered a good fit for performance across tasks. DISCUSSION: Life-span cognitive performance shows a nonlinear pattern, with gradual decline over early and mid-adulthood, followed by a transition in the 60s to notably accelerated, but more variable, decline. Some people show less decline than others, and some cognitive abilities show less within-person decline than others.

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.

Interindividual and intraindividual variability in amnestic mild cognitive impairment (aMCI) measured with an online cognitive assessment.

INTRODUCTION: Mean cognitive performance is worse in amnestic mild cognitive impairment (aMCI) compared to control groups. However, studies on variability of cognitive performance in aMCI have yielded inconclusive results, with many differences in variability measures and samples from one study to another. METHODS: We examined variability in aMCI using an existing older adult sample (n = 91; 51 with aMCI, 40 with normal cognition for age), measured with an online self-administered computerized cognitive assessment (Cogniciti's Brain Health Assessment). Our methodology extended past findings by using pure measures of variability (controlling for confounding effects of group performance or practice), and a clinically representative aMCI sample (reflecting the continuum of cognitive performance between normal cognition and aMCI). RESULTS: Between-group t-tests showed significantly greater between-person variability (interindividual variability or diversity) in overall cognitive performance in aMCI than controls, although the effect size was with a small to moderate effect size, d = 0.44. No significant group differences were found in within-person variability (intraindividual variability) across cognitive tasks (dispersion) or across trials of a response time task (inconsistency), which may be because we used a sample measuring the continuum of cognitive performance. Exploratory correlation analyses showed that a worse overall score was associated with greater inter- and intraindividual variability, and that variability measures were correlated with each other, indicating people with worse cognitive performance were more variable. DISCUSSION: The current study demonstrates that self-administered online tests can be used to remotely assess different types of variability in people at risk of Alzheimer`s. Our findings show small but significantly more interindividual differences in people with aMCI. This diversity is considered as "noise" in standard assessments of mean performance, but offers an interesting and cognitively informative "signal" in itself.