Higher Cognitive Performance Research Articles

Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis.

ObjectiveTo identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS).MethodsLinkage disequilibrium score regression and Mendelian randomization were applied in a large‐scale, data‐driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome‐wide association studies (GWASes) summary statistics from MR Base and LD‐hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed.ResultsWe have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest.InterpretationHere, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low‐desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470–481

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study.

BackgroundThere is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer’s disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging.MethodsWe included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity).FindingsYounger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without.ConclusionsResilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.

In Patients with Minor Beta-Thalassemia, Cognitive Performance Is Related to Length of Education, But not to Minor Beta-Thalassemia or Hemoglobin Levels

Objective: Thalassemia is one of the most frequent monogenic disorders, leading to impairment in the maturation and survival of red blood cells. The question examined here is whether, and if so, to what extent, people with beta-thalassemia might also be impaired in their cognitive functioning. Previous results in adults with beta-thalassemia showed cognitive impairment when compared to healthy controls. However, length of education was never taken into consideration as a possible confounder. Accordingly, the aim of the present study was to assess people with minor beta-thalassemia and compare them to healthy controls, while controlling for length of education. Method : A total of 25 adults (mean age: 29.36 years; 56% females) with beta-thalassemia and 25 healthy controls (mean age: 27.84 years; 72% females) took part in this cross-sectional study. They underwent cognitive testing (executive functions, attention, working memory), and their haemoglobin levels were assessed. Results: Cognitive performance did not significantly differ between patients with minor beta-thalassemia and healthy controls. Irrespective of group, higher cognitive performance was strongly associated with time spent in education. No gender differences were observed. Conclusion: Compared to healthy controls, cognitive performance was not impaired among patients with minor beta-thalassemia when length of education was introduced as a further co-variate. In both patients with minor beta-thalassemia and healthy controls, higher cognitive performance was associated with time spent for education. Health professionals should inform patients with minor beta-thalassemia that cognitive performance is related to the length of education and not to the health status of minor beta-thalassemia per se.

The association between sleep and dual-task performance in preterm and full-term children: an exploratory study

ObjectivesThe present study explored associations between sleep and children's dual-task performance using cognitive-motor dual tasks (eg, walking and talking). Previous research with older adults indicated correlations between higher gait variability and unfavorable sleep continuity variables. Based on this research, as a first objective, we investigated similar correlations in a sample of children. Second, we explored correlations between dual-task performance and dimensions of sleep architecture. Third, we tested moderating effects of prematurity on these associations. MethodsIn this study, 7-to 12-year-old children were tested in dual-task situations; of those, 39 were formerly preterm, and 59 were full-term born children. They were asked to walk and simultaneously perform different cognitive tasks. Gait was measured using an electronic walkway system. Sleep was measured using in–home sleep-electroencephalography. ResultsAfter accounting for age and cognition, regression analyses revealed correlations between a higher number of awakenings after sleep onset and lower dual-task performance; concerning sleep architecture, analyses revealed correlations between a higher amount of rapid-eye-movement (REM) sleep and lower gait variability. Furthermore, associations between a higher amount of slow wave sleep (SWS) and children's higher cognitive performance were found. Moderation analyses indicated no effects of prematurity. ConclusionsOur exploratory study suggests that a more disrupted sleep was related to children's poorer dual-task performance. Our findings support claims that REM sleep seems more related to performance in procedural tasks whereas SWS seems more related to performance in declarative tasks, suggesting that different sleep stages may support the processing of different performance types.

Ideal Cardiovascular Health and Cognitive Test Performance: Testing a Modified Index of Life's Simple 7 Among Older Chinese Adults.

Evidence suggests that cognitive decline in older adults is influenced by cardiovascular health (CVH), with metabolic and vascular mechanisms hypothesized to underlie the etiology of cognitive impairment. Research in high-income nations suggests that improved CVH is linked with decreased cognitive impairment risk, but it is unclear if this pattern is evident in low-income countries. Nationally-representative data collected in China were drawn from the World Health Organization's Study on global AGing and adult health Wave 1 (2007–2010; n = 11,295). Seven CVH factors were classified as “ideal” or “not ideal”: smoking and drinking frequency, body mass index, physical activity level, blood pressure, diet, and self-reported anxiety. Additionally, scores from five cognitive performance tests (immediate and delayed verbal recall, forward and backward digit span, verbal fluency) were used to create a composite cognitive function variable. Linear regression analyses tested whether ideal CVH measures were associated with higher composite cognitive performance, controlling for sociodemographic factors. As hypothesized, ideal CVH was generally associated with higher cognitive performance. Low anxiety levels and reliable access to sufficient food (including produce) were particularly associated with higher cognitive function. These results suggest early detection and controlling modifiable CVH risks may protect aging individuals in China from cognitive decline.

Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging

The default-mode network (DMN) is affected by advancing age, where particularly long-range connectivity has been consistently reported to be reduced as compared to young individuals. We examined whether there were any differences in the effects of intermittent theta-burst stimulation (iTBS) in DMN connectivity between younger and older adults, its associations with cognition and brain integrity, as well as with long-term cognitive status. Twenty-four younger and 27 cognitively normal older adults were randomly assigned to receive real or sham iTBS over the left inferior parietal lobule between two resting-state functional magnetic resonance imaging (rs-fMRI) acquisitions. Three years later, those older adults who had received real iTBS underwent a cognitive follow-up assessment. Among the younger adults, functional connectivity increased following iTBS in distal DMN areas from the stimulation site. In contrast, older adults exhibited increases in connectivity following iTBS in proximal DMN regions. Moreover, older adults with functional responses to iTBS resembling those of the younger participants exhibited greater brain integrity and higher cognitive performance at baseline and at the 3-year follow-up, along with less cognitive decline. Finally, we observed that ‘young-like’ functional responses to iTBS were also related to the educational background attained amongst older adults. The present study reveals that functional responses of the DMN to iTBS are modulated by age. Furthermore, combining iTBS and rs-fMRI in older adults may allow characterizing distinctive cognitive profiles in aging and its progression, probably reflecting network plasticity systems that may entail a neurobiological substrate of cognitive reserve.

Community-Based Activity and Sedentary Patterns Are Associated With Cognitive Performance in Mobility-Limited Older Adults.

Over the last few decades, considerable evidence shows that greater levels of aerobic exercise and cardiovascular fitness benefit cognitive performance. However, the degree to which free-living activity in community settings is related to cognitive performance remains unclear, particularly in older adults vulnerable to disability. Also, it is unknown whether the manner in which daily physical activity (PA) and sedentary time are accumulated throughout the day is associated with cognition. Cross-sectional associations between accelerometer-characterized PA and sedentary patterns and cognitive performance were examined in 1,274 mobility-limited older adults. Percent time spent in various bout lengths of PA (≥1, ≥2, and ≥5 min) and sedentary (≥1, ≥30, and ≥60 min) was defined as the number of minutes registered divided by total wear time × 100. Percent time was then tertiled for each bout length. Multiple linear regression models were used to estimate the associations between accelerometer bout variables and separate cognitive domains that included processing speed (Digit Symbol Coding; DSC), immediate and delayed recall (Hopkins Verbal Learning Test; HVLT), information processing and selective attention (Flanker), working memory (n-back), reaction time (switch and non-switch reaction time), and a composite score that averaged results from all cognitive tests. After adjusting for demographics, behavioral factors, and morbid conditions, more time spent in PA was associated with higher DSC for all bout lengths (p < 0.03 for all). Higher PA was associated with higher HVLT and global cognition scores but only for longer bout lengths (p < 0.05 for all). The association was largely driven by participants who spent the lowest amount of time performing activity while awake (p < 0.04). An inverse linear relationship was observed between total sedentary time and DSC (p = 0.02), but not for other measures of cognition. These results suggest that, while higher PA was associated with higher cognitive performance, PA’s association with memory was sensitive to bout duration. The time, but not the manner, spent in sedentary behaviors showed a minor association with executive function. Further research is warranted to characterize longitudinal changes in daily activity and sedentary patterns as potential biophysical markers of cognitive status in older adults.

DETERMINANTS OF 400 METERS TRAJECTORIES IN THE INCHIANTI-STUDY BY GENDER: WHAT DOES IT COUNT?

Background: The 400m test (400mT) is a reliable measure of mobility in highly performance subjects. It is a crucial aspect of an older individual’s capacity to maintain independence. The main purpose of the current work is to identify those modifiable factors able to preserve the ability in performing 400mT. Longitudinal data 9ys period from the InCHIANTI Study cohort will be considered. Methods: Latent Class Growth Curve models will be applied to identify two different profiles in performing 400mT. Elderly subjects with MMSE≥26 and no frail items will be considered. Predictors of 400mT were identified by logistic regression with backward stepwise approach by gender. Fit ability will be assessed by ROC curves. Separated analyses will be conducted by gender. Results: 363 participants (196M, age 70.8 ± 4.6, 167F, age 71.1 ± 4,7) were considered. Age (OR=0.72, OR=0.80), SPPB score (OR=3.74, OR=1.54) and physical activity (PA) moderate (OR=4.25, OR=3.48) were identified as possible predictors in both gender. MMSE (OR=1.56), TMT-A (OR=0.97), IL-6 (OR=0.73) and smoke (OR=0.30) seem to be characterized the men model, while hip flexion (OR=1.27), BMI (OR=0.80), Perdue (OR=1.38) and medications (OR=1.31) are women related predictors. AUC values derived are respectively 91.4% for men and 89.5% for women. Conclusions: Our results suggest two different risk profile by gender, even though PA and SPPB score are protective features in both men and women. High cognitive performance and low level of IL-6 counteract decline in 400mT in men, while in women maintenance of high muscle strength values and of good coordination are relevant.

Long-term cognitive trajectories and heterogeneity in patients with schizophrenia and their unaffected siblings.

ObjectiveThis study aimed to assess the heterogeneity and stability of cognition in patients with a non‐affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands.MethodAssessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group‐based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance.ResultsFive stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients’ alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003).ConclusionsThe cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes.

Cognitive screening of older adults using serious games: An empirical study

ObjectiveThe goal of the research is to develop three serious games using design for the older adult population, in order to evaluate the cognitive performance of older adults. Simultaneously, the games provide information about the cognitive performance of players with neurocognitive pathology that can be used by health care professionals in clinical monitoring. Subjects and methodsTwo groups of adults aged 50 years or more participated in the study. Group 1 was composed of 52 subjects with high cognitive performance attending a cultural academy and a senior university. Group 2 consisted in 51 patients with cognitive impairment recruited in the Old Age Psychiatric Unit of a university hospital. Each participant played the game and was assessed with a widely-used and well validated neuropsychological instrument (Montreal Cognitive Assessment – MoCA). Concurrent validity was tested for each cognitive domain with Spearman correlation coefficient. ResultsGroups 1 (Senior University) and 2 (Hospital) differed in relation to average age (64.8 vs. 76.5), proportion of female gender (80% vs. 74.1%), educational level and occupation. Subjects in Group 1 scored higher in all assessed cognitive domains and in total MoCA score (24.3 vs. 13.5). The overall game performance was better in Group 1 with the Maximum Level and Group 2 the Maximum Level correlated with all cognitive domains except for abstraction. ConclusionsThe research provides a useful case study in the development of Serious Games for cognitive screening, which can be used independently by players, repeatedly, as cognitive exercise. Thus, these Serious Games are relevant tools that can be used as a stimulus supplement (exercises) and continuous evaluation (normative tables) of the evolution of the players (older adult population), offering useful information (collecting and choosing the data to be analyzed) for follow-up by professionals involved in patient care.

Model of cognitive dynamics predicts performance on standardized tests

In the modern knowledge economy, success demands sustained focus and high cognitive performance. Research suggests that human cognition is linked to a finite resource, and upon its depletion, cognitive functions such as self-control and decision-making may decline. While fatigue, among other factors, affects human activity, how cognitive performance evolves during extended periods of focus remains poorly understood. By analyzing performance of a large cohort answering practice standardized test questions online, we show that accuracy and learning decline as the test session progresses and recover following prolonged breaks. To explain these findings, we hypothesize that answering questions consumes some finite cognitive resources on which performance depends, but these resources recover during breaks between test questions. We propose a dynamic mechanism of the consumption and recovery of these resources and show that it explains empirical findings and predicts performance better than alternative hypotheses. While further controlled experiments are needed to identify the physiological origin of these phenomena, our work highlights the potential of empirical analysis of large-scale human behavior data to explore cognitive behavior.

The Association between Lower Extremity Muscular Strength and Cognitive Function in a National Sample of Older Adults.

BackgroundWe evaluated the association between lower extremity muscular strength and cognition among older adults in the United States.MethodsData from the 1999–2002 National Health and Nutrition Examination Survey was used to identify 1508 older adults, between 60–85 years. Muscle strengthening activities were assessed via self-report. Participation in physical activity was determined from self-report data. The DSST was used to assess participant executive cognitive functioning tasks of pairing and free recall. A Kin-Com MP isokinetic dynamometer (Chatanooga Group Inc.) was used to assess lower extremity strength, expressed as absolute strength (N), relative strength (N/body weight in kg), and high (<245.75 N) vs. low (≤245.75 N) absolute strength based on the median levels of strength.ResultsLower extremity strength (β = 0.01; 95% CI: 0.0008–0.03; p = 0.039) was associated with higher cognitive performance, independent of age, muscle strengthening activities, physical activity and other covariates. In an adjusted multivariate logistic regression model, those with high (vs. low) strength had a 34% reduced odds of having low cognitive function (OR = 0.66; 95% CI: 0.46–0.93; p = 0.02).ConclusionIn this nationally representative sample of older adults, there was a positive association between elevated lower extremity muscular strength and cognitive functioning.

Aktywność fizyczna a kondycja psychiczna osób starszych

The aim of this article is to review current research on relationship between physical activity and chosen aspects of psychological status of elderly adults. Among many psychological aspects cognitive functions and anxiety and depression as emotional aspects were chosen. The results suggest that physical activity correlates with higher cognitive performance and lower rates of anxiety and depression.

Neurobiological findings associated with high cognitive performance in older adults: a systematic review.

We performed a systematic review using two major databases (MEDLINE and Web of Science) from January 2002 to November 2017. Quantitative analysis included nine of 4,457 studies and revealed that high-performing older adults have global preservation of the cortex, especially the anterior cingulate region, and hippocampal volumes larger than normal agers. Histological analysis of this group also exhibited decreased amyloid burden and neurofibrillary tangles compared to cognitively normal older controls. High performers that maintained memory ability after three years showed reduced amyloid positron emission tomography at baseline compared with high performers that declined. A single study on blood plasma found a set of 12 metabolites predicting memory maintenance of this group. Structural and molecular brain preservation of older adults with high cognitive performance may be associated with brain maintenance. The operationalized definition of high-performing older adults must be carefully addressed using appropriate age cut-off and cognitive evaluation, including memory and non-memory tests. Further studies with a longitudinal approach that include a younger control group are essential.

Plasma Concentrations of Lutein and Zeaxanthin, Macular Pigment Optical Density, and Their Associations With Cognitive Performances Among Older Adults

We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Higher MPOD at 0.5° was significantly associated with a higher composite z-score (β = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (β = 0.39, 95%CI 0.08-0.70), and higher IST (β = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (β = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (β = 0.12, 95%CI 0.01-0.23), along with higher IST (β = 1.02, 95%CI 0.002-2.04) and FCSRT (β = 1.55, 95%CI 0.41-2.69) performances. This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake.

F245. COGNITIVE RESERVE DIFFERENCE IN AFFECTIVE AND NONAFFECTIVE PSYCHOSIS

BackgroundThe cognitive reserve (CR) refers to the capacity of an adult brain to cope with pathology in order to minimize the symptoms (Stern, 2002). Recent studies have shown that CR is associated with clinical, functional and cognitive outcomes in patients with severe mental illness (de la Serna et al., 2013; Forcada et al., 2015; Anaya et al., 2016; Amoretti et al. ., 2016; Grande et al., 2017). Higher CR has been related to a later onset of psychosis, greater adherence and fewer psychotic symptoms (Barnett et al., 2006). However, there are no studies that evaluate longitudinally the role of CR depending on the diagnosis.The objective is to analyze the impact of CR according to the diagnosis and to study whether having a high CR may be associated with better clinical, functional and cognitive outcomes.MethodsWe gathered all the relevant clinical and sociodemographic data. All subjects were assessed clinically, neuropsychologically and functionally at baseline and after a two-year follow-up. To assess CR, three proxies have been integrated: premorbid IQ, years of education-occupation and leisure activities.To determine whether the level of CR was associated with clinical, functional and neuropsychological outcomes and whether it was different between diagnoses, a multivariate analysis of variance was used.Results285 DSM-IV patients with first episode of psychosis (FEP) were enrolled. The sample was divided into affective and non-affective groups.In the non-affective group, those with high CR are older and had a better socioeconomic status, better functioning and cognitive performance and lower symptoms, as well as a shorter duration of untreated psychosis (DUP) and a later age of onset. After 2 years of follow-up, they showed significant differences in all the cognitive domains evaluated, except for the executive functions.In the affective group, the patients with high and low CR showed differences in positive and manic symptoms, as well as in verbal memory at baseline. At 2 years of follow-up the differences were observed in functionality, positive and negative symptoms and in verbal memory. There were no significant differences in terms of age, gender, DUP, or age of onset, although significant differences were found in socioeconomic level (p = 0.038).DiscussionHigher CR can result in better recovery and functioning and in higher cognitive performance in patients with a FEP. Therefore, we propose that early interventions focused on the promotion of neuropsychological abilities and CR could reduce the harmful impact of this disease.However, it is necessary that these interventions should be personalized taking into account that CR plays a differential role according to the diagnosis.

Light Alcohol Consumption Does Not Protect Cognitive Function: A Longitudinal Prospective Study

Studies show that light to moderate alcohol consumption is related to better health and higher cognitive performance. However, it has been suggested that this association is caused by a systematic bias in the control group as many people abstain from drinking or quit because of health issues. Therefore, the group of non-drinkers is biased towards poor health and may not be suitable as a control group. The present study examined the effect of alcohol on cognitive performance while addressing this bias by excluding the non-drinkers. Thus, instead of comparing different levels of alcohol consumption to a non-drinking control group, a dose-response association was calculated between all levels of alcohol intake and cognitive performance. The study used information from a sample of people in the Swedish Twin Registry, who in their midlife (1967) participated in a survey on alcohol intake and 25 years later participated in a longitudinal study on cognitive aging (N = 486). The cognitive aging study took place on five occasions, at 2-year intervals, and included the Mini Mental State Examination (MMSE), tests of episodic memory, semantic memory and spatial ability. The association between midlife alcohol consumption and later cognitive performance was analyzed using growth curve models, adjusting for background variables. The findings showed that there was a significant negative dose-response association between alcohol intake in midlife and the MMSE, and the tests of episodic memory, such that higher intake in midlife was related to lower performance in old age. The associations between alcohol and semantic memory, and spatial ability respectively, were not significant. In contrast to findings from other studies, which show that low to moderate alcohol intake promotes cognitive function, the current study showed that alcohol intake was related to lower cognitive performance in a dose-response manner, even at low levels. The results from this study indicate that the observed benefits of moderate alcohol intake for cognitive function reported by others might be solely due to comparisons to an inappropriate control group, a group that is biased towards poor health. Hence, it is concluded that light alcohol intake may not protect cognitive function.

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

Operationalized definition of older adults with high cognitive performance.

ABSTRACTRecently, there has been an increasing number of studies on exceptional cognitive aging. Herein, we aim to objectively provide the operationalized characterization of older adults with unusually high memory ability. Some authors have defined them as “SuperAgers”, individuals aged 80 years or older with memory ability similar or superior to middle-aged subjects. On the other hand, the terminology “high-performing older adults” (HPOA) seems to appropriately conceptualize these individuals without exaggeration. A threshold for age is not a reliable criterion, but may be defined as 75 and 80 years of age for developing and developed countries, respectively. We propose that HPOA may exhibit episodic memory test scores equal to or greater than those of individuals aged 50-60 years, according to the validated tables for the respective country. This group must also have global cognition scores within expected average values for age and education. Executive functioning may play a central role in the exceptional memory performance of this group. Further studies are essential to confirm existing findings and may provide important evidence for cognitive aging theory and the neurobiology of dementia.

Individual-Specific Physical Activities on Cognitive Function among Older Adults

We evaluated the specific association between individual-specific physical activities and cognitive function among a national sample of the broader U.S. older adult population. Data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES) were used to identify 1,902 adults, between 60-85 years, with complete data on selected study variables. The DSST (Digit Symbol Substitution Test) was used to assess participant executive cognitive functioning. Individual specific physical activities were associated with higher cognitive performance. Weighted multivariable linear regressions showed bicycling (â= 4.3; 95% CI: -0.2-9.0; P=0.06), walking (â= 2.6; 95% CI: 0.3-4.9; P=0.02), yard work (â= 4.1; 95% CI: -0.1-8.4; P=0.05) and golf (â= 5.3; 95% CI: 1.3-9.3; P=0.01) were associated with higher cognitive functioning. However, when accounting for overall volume of physical activity, results showed the only activity that was statistically significantly associated with higher cognitive function was golf (â= 4.7; 95% CI: 0.6-8.7; P=0.02). In this nationally representative sample of adults, there was a positive association between engagement in individual-specific physical activities and cognitive function.