Decline In Healthy Older Adults Research Articles

Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task.

Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.

Cardiovascular Disease Risk Scores and Risk of Cognitive Decline and Dementia in Older Men and Women

AbstractBackgroundRisk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia in older adults who do not have a history of CVD remains unclear. The aim of this study was to determine whether CVD risk scores are associated with subsequent cognitive decline and dementia in initially healthy older men and women.MethodParticipants were from a prospective cohort of 19,114 individuals aged 65+ years without prior CVD event or major cognitive impairment. The Atherosclerotic Cardiovascular Disease risk score (ASCVDRS) and the Framingham risk score (FRS) were calculated at baseline, with women and men analysed separately due to large differences in overall level of CVD risk. Dementia was adjudicated by clinical experts according to DSM‐IV criteria. Cognitive decline was defined as a >1.5 SD decline in cognitive score from their own baseline value on any of the four cognitive tests looking at global cognition, episodic memory, psychomotor speed or verbal fluency.ResultOver a median follow‐up of 6.4 years, 4,325 individuals had cognitive decline and 850 individuals developed dementia. ASCVDRS, was associated with dementia and cognitive decline, in men and women, whether considered as a continuous measure and as tertiles. For example, men and women in the highest ASCVDRS tertile had a 41% and 45% increased risk of dementia compared to the lowest tertile respectively (HR [95%CI] men: 1.41 [1.08,1.85], women: 1.45 [1.11,1.89]). However, higher FRS was not associated with incident dementia and only associated with an increased risk of cognitive decline among women (FRS continuous: 1.08 [1.01,1.26]; highest vs. lowest tertiles: 1.13 [1.01‐1.26]).ConclusionThese results provide some evidence for ASCVDRS as a measure of shared CVD risk factors for identifying/predicting risk of dementia and cognitive decline in healthy older adults regardless of sex. Further research is needed to confirm the findings and to validate these results in more heterogeneous populations.

Time-Based and Event-Based Prospective Memory in Mild Cognitive Impairment and Alzheimer's Disease Patients: A Systematic Review and Meta-analysis.

Prospective memory (PM) is the ability to remember to perform planned actions in a future moment and it is of fundamental importance for an independent and autonomous lifestyle from development to late adulthood. Deficits in episodic memory and executive functions, which are involved in PM are characteristic features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Considering that the number of older adults is drastically increasing over the next decades, it is of great interest to understand how PM decline in healthy older adults and patients with different degree of cognitive decline. The present meta-analysis included 46 studies investigating PM performance in AD patients (17 studies) and people with MCI (24 studies); 5 studies included both clinical conditions in the same article. The 46 studies contributed a total of 63 independent samples and 129 effect sizes from 4668 participants (2115 patients and 2553 controls). Unlike previous reviews of the literature, our results with a larger and updated sample of studies confirmed lower PM abilities in AD compared to MCI and controls, although we did not observe conclusive differences between event-based and time-based PM in patients. Surprisingly, PM deficits shown by MCI and AD patients have decreased across years, in parallel to a reduction of the evidence of publication bias and an increase in the number of observations per task. We propose the use of more reliable research designs as one plausible explanation for the reduction of PM impairments.

The combined effect of β ‐amyloid and white matter hyperintensities on present and future executive function performance in cognitively normal older adults

AbstractBackgroundβ‐amyloid (Aβ) and White matter hyperintensities (WMH) are key drivers of cognitive decline in healthy older adults and both are considered biomarkers of preclinical dementia. Deficit in executive function (EF) linked to WMHs and Aβ burden, have been shown to predict the development of dementia. The present study aimed to explore the interactions of regional and global Aβ with WMH on baseline and longitudinal performance in EF in cognitively normal (CN) older adults.MethodGlobal and regional Standard Uptake Value ratios (SUVr) from Aβ‐PET, WMH volumes from MRI FLAIR images, and composite scores of EF at baseline and after approximately 2 years were analyzed across a sample of 714 clinically‐normal (Mini‐Mental State Examination (MMSE) ≥ 26), aged participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI2). We used multiple regression models including the interaction tem and main effects for Aβ and WMH to investigate the independent and combined associations of these pathologies with EF. Age, ApoE, education, baseline EF score, and time to follow up EF testing were entered as covariates in the regression models.ResultThe moderation regression analysis showed that additive effects on Aβ burden and WMH in relation to baseline EF with p value for the interaction term between the two pathologies 0.07, and significant interaction effects of global, frontal and cingulate Aβ burden, and WMH in relation to longitudinal EF performance with p values of 0.037, 0.03, and 0.032 respectively. The main effect from regression analysis demonstrated that baseline EF performance was predicted by the combination of Aβ burden and WMH, while Aβ burden was the only predictor for longitudinal EF performance.ConclusionThese data demonstrated that baseline Aβ and WMHs have both independent effects on EF scores at baseline and synergistic effects on longitudinal EF performance. The biological relationships and interplay between Ab and WMH responsible for the synergistic effects seen on longitudinal EF performance warrants further study.

Advanced Brain Age and Chronic Poststroke Aphasia Severity.

Chronic poststroke language impairment is typically worse in older individuals or those with large stroke lesions. However, there is unexplained variance that likely depends on intact tissue beyond the lesion. Brain age is an emerging concept, which is partially independent from chronologic age. Advanced brain age is associated with cognitive decline in healthy older adults; therefore, we aimed to investigate the relationship with stroke aphasia. We hypothesized that advanced brain age is a significant factor associated with chronic poststroke language impairments, above and beyond chronologic age, and lesion characteristics. This cohort study retrospectively evaluated participants from the Predicting Outcomes of Language Rehabilitation in Aphasia clinical trial (NCT03416738), recruited through local advertisement in South Carolina (US). Primary inclusion criteria were left hemisphere stroke and chronic aphasia (≥12 months after stroke). Participants completed baseline behavioral testing including the Western Aphasia Battery-Revised (WAB-R), Philadelphia Naming Test (PNT), Pyramids and Palm Trees Test (PPTT), and Wechsler Adult Intelligence Scale Matrices subtest, before completing 6 weeks of language therapy. The PNT was repeated 1 month after therapy. We leveraged modern neuroimaging techniques to estimate brain age and computed a proportional difference between chronologic age and estimated brain age. Multiple linear regression models were used to evaluate the relationship between proportional brain age difference (PBAD) and behavior. Participants (N = 93, 58 males and 35 females, average age = 61 years) had estimated brain ages ranging from 14 years younger to 23 years older than chronologic age. Advanced brain age predicted performance on semantic tasks (PPTT) and language tasks (WAB-R). For participants with advanced brain aging (n = 47), treatment gains (improvement on the PNT) were independently predicted by PBAD (T = -2.0474, p = 0.0468, 9% of variance explained). Through the application of modern neuroimaging techniques, advanced brain aging was associated with aphasia severity and performance on semantic tasks. Notably, therapy outcome scores were also associated with PBAD, albeit only among participants with advanced brain aging. These findings corroborate the importance of brain age as a determinant of poststroke recovery and underscore the importance of personalized health factors in determining recovery trajectories, which should be considered during the planning or implementation of therapeutic interventions.

Surgical Hospitalization Is Not Associated With Cognitive Trajectory Over 6Years in Healthy Older Australians.

The aim was to investigate the association of cognitive trajectories and overnight surgical hospitalization in older adults, while controlling for and comparing to the association with acute medical hospitalizations. This is a secondary analysis of data from a population-based, longitudinal cohort study of older Australians. Cognition was assessed with 4 biennial waves of prospective neuropsychological data from 1026 Sydney Memory and Aging Study participants age 70 to 90years at baseline. Hospitalization exposure was obtained from 10years of electronically linked data from the New South Wales Admitted Patient Data Collection. Latent growth curve modeling estimated global cognition z-score baseline and slope over 6years, and the effects of contemporaneous surgical and medical hospitalization predictors while controlling for potential demographic and comorbidity confounders. After controlling for confounding variables, this analysis showed that overnight surgical hospitalizations were not associated with worse baseline global cognition or accelerated cognitive decline over 6years. This was despite this cohort having more surgeries and more complex surgeries compared with Australian data for overnight hospitalizations in over 70-year-olds. Conversely, recent medical hospitalizations were associated with accelerated cognitive decline. This analysis finds that surgery and anesthesia are unlikely to be risk factors for medium to long-term global cognitive decline in healthy older adults, while controlling for contemporaneous medical hospitalizations. These findings are contrary to prior conclusions from several surgical studies that may have been impeded by insufficient comparison groups. They are, however, consistent with recent population-based studies suggesting surgery has minimal association with cognitive decline in the medium to long-term. Future research needs to clarify the association of surgical hospitalization with the full spectrum of cognitive outcomes including subjective cognitive complaints and dementia, and importantly, how these cognitive outcomes correlate with clinically significant functional changes.

Mediation of perceived stress and cortisol in the association between neuroticism and global cognition in older adults: Alongitudinal study.

Neuroticism has been associated with a greater dementia risk, but its association with cognitive decline in healthy older adults remains unclear. Stress has been proposed as one of the mechanisms that could explain this relationship. Our aim was to analyse, in healthy older people, the mediating role of perceived stress and the Hypothalamic-Pituitary-Adrenal (HPA) axis in the association between neuroticism and global cognition. At Waves 1 and 2 (4-year follow-up), 87 older people (49.4% women; M age=65.08, SD=4.54 at Wave 1) completed a neuropsychological battery and the Perceived Stress Scale (PSS), and provided saliva samples on two (Wave 1) and three (Wave 2) consecutive days to measure the wake-to-bed slope. In Wave 2, neuroticism was assessed with the NEO-Five-Factor Inventory. PSS, but not the wake-to-bed slope, mediated the negative associations between neuroticism and global cognition (Waves 1, 2 and change). Regarding gender differences, PSS (Waves 1, 2 and change) and the wake-to-bed slope (Wave 2 and change) mediated these associations in men. Our results suggest that perceived stress and HPA-axis dysregulation could act as mechanisms underlying the association between neuroticism and cognitive functioning and decline, at least in older men.

A Systematic Review and Meta-Analysis of Transcranial Direct Current Stimulation to Remediate Age-Related Cognitive Decline in Healthy Older Adults.

BackgroundTranscranial direct current stimulation (tDCS) has been proposed as a possible method for remediating age-associated cognitive decline in the older adult population. While tDCS has shown potential for improving cognitive functions in healthy older adults, stimulation outcomes on various cognitive domains have been mixed.MethodsA systematic search was performed in four databases: PubMed, EMBASE, Web of Science, and PsychInfo. Search results were then screened for eligibility based on inclusion/exclusion criteria to only include studies where tDCS was applied to improve cognition in healthy older adults 65 years and above. Eligible studies were reviewed and demographic characteristics, tDCS dose parameters, study procedures, and cognitive outcomes were extracted. Reported effect sizes for active compared to sham group in representative cognitive domain were converted to Hedges’ g.Main ResultsA total of thirteen studies involving healthy older adults (n=532, mean age=71.2+5.3 years) were included in the meta-analysis. The majority of included studies (94%) targeted the prefrontal cortex with stimulation intensity 1–2 mA using various electrode placements with anodes near the frontal region. Across all studies, we found Hedges’ g values ranged from −0.31 to 1.85 as reported group effect sizes of active stimulation compared to sham.ConclusionWhile observed outcomes varied, overall findings indicated promising effects of tDCS to remediate cognitive aging and thus deserves further exploration. Future characterization of inter-individual variability in tDCS dose response and applications in larger cohorts are warranted to further validate benefits of tDCS for cognition in healthy older adults.

Egg intake moderates the rate of memory decline in healthy older adults.

Eggs contain important compounds related to enhanced cognition, but it is not clear if egg consumption, as a whole, has a direct impact on memory decline in older adults. This study aimed to determine whether egg intake levels predict the rate of memory decline in healthy older adults after sociodemographic and dietary controls. We conducted a secondary analysis of data from 470 participants, age 50 and over, from the Biospsychosocial Religion and Health Study. Participants completed a food frequency questionnaire, which was used to calculate egg intake and divide participants into Low (<23 g/week, about half an egg), Intermediate (24-63 g/week, half to 1½ eggs) and High (≥63 g/week, about two or more eggs) tertiles. Participants were administered the California Verbal Learning Test - 2nd Edition (CVLT-II) Short Form in 2006-2007, and 294 of them were again tested in 2010-2011. Using linear mixed model analysis, no significant cross-sectional differences were observed in CVLT-II performance between egg intake levels after controlling for age, sex, race, education, body mass index, cardiovascular risk, depression and intake of meat, fish, dairy and fruits/vegetables. Longitudinally, the Intermediate egg group exhibited significantly slower rates of decline on the CVLT-II compared to the Low egg group. The High egg group also exhibited slower rates of decline, but not statistically significant. Thus, limited consumption of eggs (about 1 egg/week) was associated with slower memory decline in late life compared to consuming little to no eggs, but a dose-response effect was not clearly evident. This study may help explain discrepancies in previous research that did not control for other dietary intakes and risk factors.

Schizophrenia polygenic risk predicts general cognitive deficit but not cognitive decline in healthy older adults

There has been a long argument over whether schizophrenia is a neurodegenerative disorder associated with progressive cognitive impairment. Given high heritability of schizophrenia, ascertaning if genetic susceptibility to schizophrenia is also associated with cognitive decline in healthy people would support the view that schizophrenia leads to an accelerated cognitive decline. Using the population representative sample of 6817 adults aged >50 years from the English Longitudinal Study of Ageing, we investigated associations between the biennial rate of decline in cognitive ability and the schizophrenia polygenic score (SZ-PGS) during the 10-year follow-up period. SZ-PGS was calculated based on summary statistics from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Cognition was measured sequentially across four time points using verbal memory and semantic fluency tests. The average baseline verbal memory was 10.4 (SD = 3.4) and semantic fluency was 20.7 (SD = 6.3). One standard deviation (1-SD) increase in SZ-PGS was associated with lower baseline semantic fluency (β = −0.25, 95%CI = −0.40 to −0.10, p = 0.002); this association was significant in men (β = −0.36, 95%CI = −0.59 to −0.12, p = 0.003) and in those who were aged 60–69 years old (β = −0.32, 95%CI = −0.58 to −0.05, p = 0.019). Similarly, 1-SD increase in SZ-PGS was associated with lower verbal memory score at baseline in men only (β = −0.12, 95%CI = −0.23 to −0.01, p = 0.040). However, SZ-PGS was not associated with a greater rate of decline in these cognitive domains during the 10-year follow-up. Our findings highlight that while genetic susceptibility to schizophrenia conveys developmental cognitive deficit, it is not associated with an ongoing cognitive decline, at least in later life. These results do not support the neo-Kraepelinian notion of schizophrenia as a genetically determined progressively deteriorating brain disease.

Good test-retest reliability of a paired-pulse transcranial magnetic stimulation protocol to measure short-interval intracortical facilitation.

Transcranial magnetic stimulation (TMS) is used frequently to study human physiology, including the indirect-wave (I-wave) circuits generating short-interval intracortical facilitation (SICF). Growing evidence implicates SICF in plasticity and motor learning, suggesting that SICF is likely of functional relevance in both health and disease. To date, test-retest reliability has not been established for measures of SICF: given the clear potential of SICF to be used as a diagnostic tool, it is critical to establish the reliability of the paired-pulse TMS protocol to measure SICF. We investigated the test-retest reliability of SICF measured using paired-pulse TMS. SICF was measured in two sessions in 20 young adults using single- and paired-pulse TMS. Single-pulse TMS was set at an intensity that elicited MEPs of 1mV (SI1mV) and paired-pulse TMS was set with the first stimulus at SI1mV, the second stimulus (S2) 90% of resting motor threshold (RMT), and a total of 20 interstimulus intervals (ISI; 1.1-4.9ms with a 0.2ms step). Large intraclass correlation coefficients (ICC) indicate good test-retest reliability between sessions for all SICF peaks (ICCs ranging from 0.73 to 0.79). The ISI at which SICF was maximal within individuals was consistent at all three peaks across both experimental sessions. Results showed good test-retest reliability of SICF at all three peaks when using a standard paired-pulse protocol to measure SICF. This finding suggests that paired-pulse TMS can be used to reliably probe the excitability of the interneuronal circuits that generate SICF. This provides a strong platform for future research to investigate the functional role of I-wave circuitry, including the role of I-wave circuitry in motor control decline in healthy older adults and individuals with movement disorders.

The Role of Resting-State Network Functional Connectivity in Cognitive Aging.

Aging is associated with disruptions in the resting-state functional architecture of the brain. Previous studies have primarily focused on age-related declines in the default mode network (DMN) and its implications in Alzheimer’s disease. However, due to mixed findings, it is unclear if changes in resting-state network functional connectivity are linked to cognitive decline in healthy older adults. In the present study, we evaluated the influence of intra-network coherence for four higher-order cognitive resting-state networks on a sensitive measure of cognitive aging (i.e., NIH Toolbox Fluid Cognition Battery) in 154 healthy older adults with a mean age of 71 and education ranging between 12 years and 21 years (mean = 16). Only coherence within the cingulo-opercular network (CON) was significantly related to Fluid Cognition Composite scores, explaining more variance in scores than age and education. Furthermore, we mapped CON connectivity onto fluid cognitive subdomains that typically decline in advanced age. Greater CON connectivity was associated with better performance on episodic memory, attention, and executive function tasks. Overall, the present study provides evidence to propose CON coherence as a potential novel neural marker for nonpathological cognitive aging.

Mindwandering propensity modulates episodic memory consolidation

Research into strategies that can combat episodic memory decline in healthy older adults has gained widespread attention over the years. Evidence suggests that a short period of rest immediately after learning can enhance memory consolidation, as compared to engaging in cognitive tasks. However, a recent study in younger adults has shown that post-encoding engagement in a working memory task leads to the same degree of memory consolidation as from post-encoding rest. Here, we tested whether this finding can be extended to older adults. Using a delayed recognition test, we compared the memory consolidation of word–picture pairs learned prior to 9 min of rest or a 2-Back working memory task, and examined its relationship with executive functioning and mindwandering propensity. Our results show that (1) similar to younger adults, memory for the word–picture associations did not differ when encoding was followed by post-encoding rest or 2-Back task and (2) older adults with higher mindwandering propensity retained more word–picture associations encoded prior to rest relative to those encoded prior to the 2-Back task, whereas participants with lower mindwandering propensity had better memory performance for the pairs encoded prior to the 2-Back task. Overall, our results indicate that the degree of episodic memory consolidation during both active and passive post-encoding periods depends on individual mindwandering tendency.

Prevention of Cognitive Decline in Healthy Older Adults: An Integrative Review

Prevention of Cognitive Decline in Healthy Older Adults: An Integrative Review

Influence of working memory and executive function on stair ascent and descent in young and older adults

This study assessed the influence of attention division, working memory and executive function on stair ascent and descent in young and older adults. Twenty young (25.5 ± 2.1 yrs) and 20 older adults (68.4 ± 5.4 yrs) ascended and descended a 3-step staircase with no simultaneous cognitive task (single-motor task) or while performing a cognitive task (dual-task condition). The cognitive task involved either 1) recalling a word list of the subject's word-span minus 2 words (SPAN-2) to assess the attention division effect, 2) a word list of subject's word-span (SPAN-O) to assess the working memory effect, or 3) recalling in alphabetical order, a word list of the subject's word-span (SPAN-A) to assess the executive function effect. Word-span corresponds to the longest string of words that can be recalled correctly. The duration of ascent and descent of stairs was used to assess the cognitive-motor interaction.Stair ascent and descent duration did not differ between age groups for the single-motor task, and was similar between single-motor task and SPAN-2 in both groups (p > 0.05). In contrast, stair ascent and descent duration increased with SPAN-O compared with SPAN-2 for both groups (p < 0.01). Stair ascent (p = 0.017) and descent (p = 0.008) were longer in SPAN-A than SPAN-O only in older adults.Healthy aging was not associated with a decrease in the capacity to perform motor-cognitive dual tasks that involved ascending and descending of stairs when the cognitive task only required working memory. However, the decrease in dual-task performance involving executive functioning may reflect a subclinical cognitive decline in healthy older adults.

Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936.

ObjectivesIn this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes.MethodsWe used data from the Lothian Birth Cohort 1936 (n at Waves 1–3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes.ResultsBaseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load.ConclusionsOur results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.

Strategies for Preventing Cognitive Decline in Healthy Older Adults

Many advances have been made in the understanding of age-related changes in cognition. As research details the cognitive and neurobiological changes that occur in aging, there is increased interest in developing and understanding methods to prevent, slow, or reverse the cognitive decline that may occur in normal healthy older adults. The Institute of Medicine has recently recognized cognitive aging as having important financial and public health implications for society with the increasing older adult population worldwide. Cognitive aging is not dementia and does not result in the loss of neurons but rather changes in neurotransmission that affect brain functioning. The fact that neurons are structurally intact but may be functionally affected by increased age implies that there is potential for remediation. This review article presents recent work using medication-based strategies for slowing cognitive changes in aging. The primary method presented is a hormonal approach for affecting cognition in older women. In addition, a summary of the work examining modifiable lifestyle factors that have shown promise in benefiting cognition in both older men and women is described. Much work remains to be done so that evidence-based recommendations can be made for slowing cognitive decline in healthy older adults. The success of some of these methods thus far indicates that the brains of healthy older adults are plastic enough to be able to respond to these cognitive decline prevention strategies, and further work is needed to define the most beneficial methods.

U.S. GERIATRIC INTERVENTION STUDY TO PREVENT COGNITIVE IMPAIRMENT AND DISABILITY (U.S.-FINGER)

Lifestyle interventions focused on combining healthy nutrition, physical activity, and social and intellectual challenge may represent a promising therapeutic strategy to protect brain health. The recent results of the population-based 2-year clinical trial, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), indicated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of heart health risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. As yet, there are no pharmacological treatment options that can rival this effect. Thus, there is an urgent need to expand this work to test the generalizability, adaptability, and sustainability of their findings in diverse and global populations. The U.S. Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (US-FINGER) trial builds on lessons learned from FINGER and will test a 2-year multi-site and community-based multidomain intervention of physical activity, nutritional guidance, cognitive training and social activities, and management of medical co-morbidities in asymptomatic older adults aged 60–79 years. Study candidates will be identified through medical history to assess dementia risk using an algorithm that includes vascular and other established predictors. Family history of dementia and physical activity level will also be queried using follow-up questionnaires for those identified through the algorithm. A cognitive composite score focused on episodic memory and executive function will serve as the primary outcome. An overview of the study design, target population and recruitment approach, interventions, outcomes, and implementation strategies for US-FINGER will be discussed. In the absence of other effective treatment options and in the wake of promising findings from FINGER, there is a pressing need to replicate FINGER in diverse and larger populations. US-FINGER hopes to expand the scientific footprint of the Finnish study and test the generalizability, adaptability, and sustainability of a multidomain behavioral intervention to effectively prevent cognitive decline and progression to Alzheimer's dementia.

LASTING IMPROVEMENT OF ASSOCIATIVE MEMORY IN OLDER ADULTS THROUGH TRANSCRANIAL MAGNETIC STIMULATION

AbstractAssociative memory is one of the cognitive domains most vulnerable to cognitive aging. Repetitive transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation method to enhance cognition. Multiple-session rTMS has been used as neurological assistant treatment for MCI and AD patients. However, whether rTMS could ameliorate memory decline in healthy older adults remains unknown. The dorsolateral prefrontal cortex (DLPFC) is critically involved in associative memory, and is accessible by the rTMS. Hence we wondered whether application of rTMS to the DLPFC improve associative memory in older adults. In addition, we were also concerned about the lasting effects of memory improvement after the rTMS.Here we applied ten sessions of rTMS (10 Hz) to the right DLPFC of normal older adults in a double blind design with well-matched experimental and sham groups. The cognitive performances including executive function, working memory, and associative memory were assessed before and after the rTMS or sham stimulation. In addition, the follow-up assessment of the cognitive performances was examined one month after the last session of stimulation. Results showed that rTMS selectively improved associative memory performance. Importantly, the memory enhancement persisted one month after the brain stimulation. Our findings offer a promising neuroenhancement technique to counteract cognitive aging in the healthy aging people.

Individual Differences in Cognitive Function in Older Adults Predicted by Neuronal Selectivity at Corresponding Brain Regions.

Relating individual differences in cognitive abilities to neural substrates in older adults is of significant scientific and clinical interest, but remains a major challenge. Previous functional magnetic resonance imaging (fMRI) studies of cognitive aging have mainly focused on the amplitude of fMRI response, which does not measure neuronal selectivity and has led to some conflicting findings. Here, using local regional heterogeneity analysis, or Hcorr, a novel fMRI analysis technique developed to probe the sparseness of neuronal activations as an indirect measure of neuronal selectivity, we found that individual differences in two different cognitive functions, episodic memory and letter verbal fluency, are selectively related to Hcorr-estimated neuronal selectivity at their corresponding brain regions (hippocampus and visual-word form area, respectively). This suggests a direct relationship between cognitive function and neuronal selectivity at the corresponding brain regions in healthy older adults, which in turn suggests that age-related neural dedifferentiation might contribute to rather than compensate for cognitive decline in healthy older adults. Additionally, the capability to estimate neuronal selectivity across brain regions with a single data set and link them to cognitive performance suggests that, compared to fMRI-adaptation—the established fMRI technique to assess neuronal selectivity, Hcorr might be a better alternative in studying normal aging and neurodegenerative diseases, both of which are associated with widespread changes across the brain.