Age-related Changes In Cognitive Function Research Articles

Connectome-based predictive modelling of ageing, overall cognitive functioning and memory performance.

Resting-state functional magnetic resonance imaging (rs-fMRI) and brain functional connectome (we use 'brain connectome' hereafter for simplicity) have advanced our understanding of the ageing brain and age-related changes in cognitive function. Previous studies have investigated the association among brain connectome and age, global cognition, and memory function separately. However, very few have predicted age, overall cognitive functioning and memory performance in a single study to better understand their complex relationship. In this cross-sectional study, we applied an exploratory, data-driven method to investigate the brain connectome markers that could predict ageing, overall cognitive functioning assessed as intelligence quotient (IQ, measured by Wechsler Memory Scale) and memory performance assessed as memory quotient (MQ, measured by Wechsler Memory Scale) in a carefully designed, multicentre, normal ageing cohort (n = 313). Our results showed that brain connectome could predict ageing and IQ, but the association with MQ was weak. We found that the connectivity with orbital frontal cortex was associated with both ageing and IQ. Mediation analysis further showed that the brain connectome mediated the relationship between age and overall cognitive functioning, suggesting a protective brain connectomic mechanism for maintaining normal cognitive functions during healthy ageing. This work may shed light on the potential neural correlates of healthy ageing, overall cognitive functioning and memory performance.

Cannabis Use and Age-Related Changes in Cognitive Function From Early Adulthood to Late Midlife in 5162 Danish Men.

Cannabis is by far the most widely used and abused drug listed on the Drug Enforcement Administration's Schedule I, which includes drugs with a high potential for abuse. There is evidence of short-term negative effects of cannabis use on cognition, but only a limited number of studies have explored the association between cannabis use and age-related cognitive decline. The aim of the present study was to investigate the relationship between cannabis use and age-related cognitive decline from early adulthood to late midlife. The study population consisted of 5162 men who had participated in Danish follow-up studies on cognitive aging. These studies included scores on the military intelligence test Børge Prien's Prøve from both the conscription assessment (mean age=20years; p1 and p99: 18 and 26years) and from the follow-up (mean age=64years; p1 and p99: 55 and 72years) as well as extensive data on lifestyle and health from the follow-up questionnaires. The association between cannabis use and age-related cognitive decline was investigated in linear regression models. Men with a history of cannabis use had less cognitive decline from early adulthood to late midlife compared to men without a history of cannabis use. Among cannabis users, neither age of initiation of cannabis use nor frequent use was significantly associated with a greater age-related cognitive decline. In a sample of more than 5000 men followed for a mean of 44years, we found no significant harmful effects of cannabis use on age-related cognitive decline.

Exploring the Influence of Fok1/Apa1 Polymorphic Variants on Adolescent Mental Health and Response to Vitamin D Supplementation in Embryonic Hippocampal Cell Lines.

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson's and Alzheimer's diseases. This study aimed to establish the association between Fok1/Apa1 polymorphic variants and anxious/depressive symptoms in nonclinical adolescents from central Italy, with the goal of identifying the risk of developing both symptoms. We found no significant difference in genotype distribution or dominant/recessive models of Fok1/Apa1 VDR polymorphic variants between subjects with anxious/depressive symptoms and controls. HN9.10e cell lines carrying the AA genotype for Fok1 and the CC genotype for Apa1 responded better to treatment with vitamin D3 than cell lines carrying the AG genotype for Fok1 and CA genotype for Apa1. Cell lines carrying the GG genotype for Fok1 and the AA genotype for Apa1 did not respond at all, suggesting avenues for future studies in both the general population and individuals with mental and/or neuropsychiatric disorders. These studies suggest that the level of response to vitamin D3 administered to prevent and/or treat mental or neurological disorders could depend on the polymorphic variants of the vitamin D receptor.

Individual features of the temporal dynamics of inhibitory processes in visual short-term memory depending on the content of stimuli and memorization training

Introduction. Age-related changes in cognitive functions are caused by various processes: degrading inhibitory control, decrease in the volume of working memory, or a slowdown in the speed of thought processes. However, there is no unanimous opinion on the dynamics of these processes and their interactions yet. Based on this, our research goal became finding the temporal dynamics and individual relationship of the effects of proactive interference (Retrival-Induced Forgeting (RIF)) and learning to remember (Retrieval-Based Learning (RBL)) depending on the content of the presented stimuli as well as the age-related specifics of memorization when training the short-term visual memory. Materials and methods. Memory training was carried out in a mode independently organized by the study participants using a computerized memorization program in a proactive interference model, including five sessions of visual presentation of stimuli. University students participated in the first part of the study, aimed at clarifying the meaning of the content of two different sets of stimuli, (220 people, 20.4 ± 1.9 years old), whereas second part aimed to determine the age-related characteristics of visual short-term memory training in a group of students, (70 subjects, 21.7±2.5 years) and a group of elderly women (25 subjects, 64.4±6.3 years). Research results. The results of the memory trace retrieval analysis showed that the RIF effect dominates over the RBL effect regardless of the content of the stimuli, but at different rates of its development depending on the set of stimuli used. With significant individual diversity in the combination of memory strategies, the RIF effect dominated at the initial stage of stimulus presentation (67.6% of cases) and gradually replaced by RBL (56.2% in the fifth run of the experiment). Analysis of age-related characteristics of the effectiveness of short-term visual memory training showed that when it is independently organized, maintaining activity is observed in 32% of university students and 50% in the elderly group. Along with this. Only average of ten approaches to complete this task accompanied by a further decrease in the number of training participants. Comparison of the results of the first three training sessions revealed a significant increase in the memory index in both groups compared to the initial value and the presence of a RIF effect with a further more rapid increase in the efficiency of memorization in students. Conclusion. Proactive interference while memorization of visual stimuli repeatedly presented in five sessions, appears regardless of their content, age of the subjects and memorization training. The efficiency of memorization due to training grows faster in the group of students and accompanied by the combination of the RIF and RBL effects that is characterized by individual diversity without a significant effect on the final result of the memory retrieval.

Longitudinal Sleep Patterns and Cognitive Impairment in Older Adults

Sleep disturbances and clinical sleep disorders are associated with all-cause dementia and neurodegenerative conditions, but it remains unclear how longitudinal changes in sleep impact the incidence of cognitive impairment. To evaluate the association of longitudinal sleep patterns with age-related changes in cognitive function in healthy older adults. This cross-sectional study is a retrospective longitudinal analyses of the Seattle Longitudinal Study (SLS), which evaluated self-reported sleep duration (1993-2012) and cognitive performance (1997-2020) in older adults. Participants within the SLS were enrolled as part of a community-based cohort from the Group Health Cooperative of Puget Sound and Health Maintenance Organization of Washington between 1956 and 2020. Data analysis was performed from September 2020 to May 2023. The main outcome for this study was cognitive impairment, as defined by subthreshold performance on both the Mini-Mental State Examination and the Mattis Dementia Rating Scale. Sleep duration was defined by self-report of median nightly sleep duration over the last week and was assessed longitudinally over multiple time points. Median sleep duration, sleep phenotype (short sleep, median ≤7 hours; medium sleep, median = 7 hour; long sleep, median ≥7 hours), change in sleep duration (slope), and variability in sleep duration (SD of median sleep duration, or sleep variability) were evaluated. Of the participants enrolled in SLS, only 1104 participants who were administered both the Health Behavior Questionnaire and the neuropsychologic battery were included for analysis in this study. A total of 826 individuals (mean [SD] age, 76.3 [11.8] years; 468 women [56.7%]; 217 apolipoprotein E ε4 allele carriers [26.3%]) had complete demographic information and were included in the study. Analysis using a Cox proportional hazard regression model (concordance, 0.76) showed that status as a short sleeper (hazard ratio, 3.67; 95% CI, 1.59-8.50) and higher sleep variability (hazard ratio, 3.06; 95% CI, 1.14-5.49) were significantly associated with the incidence of cognitive impairment. In this community-based longitudinal study of the association between sleep patterns and cognitive performance, the short sleep phenotype was significantly associated with impaired cognitive performance. Furthermore, high sleep variability in longitudinal sleep duration was significantly associated with the incidence of cognitive impairment, highlighting the possibility that instability in sleep duration over long periods of time may impact cognitive decline in older adults.

Epigenetic Age Acceleration and Chronological Age: Associations With Cognitive Performance in Daily Life.

DNA methylation-derived epigenetic clocks offer the opportunity to examine aspects of age acceleration (ie, the difference between an individual's biological age and chronological age), which vary among individuals and may better account for age-related changes in cognitive function than chronological age. Leveraging existing ambulatory cognitive assessments in daily life from a genetically diverse sample of 142 adults in midlife, we examined associations between 5 measures of epigenetic age acceleration and performance on tasks of processing speed and working memory. Covarying for chronological age, we used multilevel models to examine associations of epigenetic age acceleration (Horvath 1, Horvath 2, Hannum, PhenoAge, and GrimAge clocks) with both average level and variability of cognitive performance. Positive age acceleration (ie, epigenetic age greater than chronological age) was associated with poorer mean processing speed (Horvath 1 and 2) and working memory (GrimAge). Higher chronological age was also associated with poorer mean processing speed and working memory performance. Further, positive age acceleration was generally associated with greater intraindividual variability in working memory and processing speed tasks, whereas being chronologically older was associated with less intraindividual variability. Although further work is needed, our results indicate age acceleration effects have comparable or greater size as those for chronological age differences, suggesting that epigenetic age acceleration may account for additional risk and interindividual variation in cognitive performance above chronological age.

Does serum neurofilament light help predict accelerated cognitive ageing in unimpaired older adults?

Neurofilament light (NfL) is a blood biomarker of neurodegeneration. While serum NfL levels have been demonstrated to increase with normal ageing, the relationship between serum NfL levels and normal age-related changes in cognitive functions is less well understood. The current study investigated whether cross-sectional serum NfL levels measured by single molecule array technology (Simoa®) mediated the effect of age on cognition, measured by a battery of neuropsychological tests administered biannually for 8 years, in a cohort of 174 unimpaired older adults (≥50 years) from the Tasmanian Healthy Brain Project. Mediation analysis was conducted using latent variables representing cognitive test performance on three cognitive domains - episodic memory, executive function, and language (vocabulary, comprehension, naming). Cognitive test scores for the three domains were estimated for each participant, coincident with blood collection in 2018 using linear Bayesian hierarchical models. Higher serum NfL levels were significantly positively associated with age (p < 0.001 for all domains). Cognitive test scores were significantly negatively associated with age across the domains of executive function (p < 0.001), episodic memory (p < 0.001) and language (p < 0.05). However, serum NfL levels did not significantly mediate the relationship between age and cognitive test scores across any of the domains. This study adds to the literature on the relationship between serum NfL levels and cognition in unimpaired older adults and suggests that serum NfL is not a pre-clinical biomarker of ensuing cognitive decline in unimpaired older adults.

Frequency of cognitive impairment in older forensic inpatients: results of a pilot cross-sectional study

ABSTRACT The number of older inpatients in forensic hospitals is growing. Overall, complex needs in treatment are identified for this group, and differ significantly from those of younger forensic patients. To date, there has been little awareness of the relevance of age-related changes in cognitive function of older forensic patients. Data on the prevalence of cognitive disorders in older forensic inpatients are rare, and, for German forensic hospitals, completely lacking. Against this background, a pilot project was conducted in forensic departments of five Psychiatric hospitals in North Rhine Westphalia, Germany. Sociodemographics, crime-related characteristics and medical data of inpatients aged 60 years and older were collected. Established cognitive screening instruments were administered. 34 of 134 forensic patients aged 60–91 years participated in the study. Dependent on the instrument used, up to 65% showed impairment in global cognitive functioning and up to 68% showed executive dysfunctions. Our pilot data indicate that cognitive impairment in older forensic patients in Germany is more frequent than reported for the older general population in Germany. Based on the findings, the extent to which diagnostic routines should be implemented and the complex factors (e.g. the underlying mental illness) that need to be taken into account are discussed.

A pilot voxel-based morphometry study of older adults after the PICMOR intervention program

BackgroundAge-related decline in cognitive function, such as executive function, is associated with structural changes in the neural substrates, such as volume reductions in the lateral prefrontal cortex. To prevent or delay age-related changes in cognitive function, cognitive intervention methods that employ social activity, including conversations, have been proposed in some intervention studies. Interestingly, previous studies have consistently reported that verbal fluency ability can be trained by conversation-based interventions in healthy older adults. However, little is known about the neural substrates that underlie the beneficial effect of conversation-based interventions on cognitive function. In this pilot study, we aimed to provide candidate brain regions that are responsible for the enhancement of cognitive function, by analyzing structural magnetic resonance imaging (MRI) data that were additionally obtained from participants in our previous intervention study.MethodsA voxel-based morphometric analysis was applied to the structural MRI data. In the analysis, the regional brain volume was compared between the intervention group, who participated in a group conversation-based intervention program named Photo-Integrated Conversation Moderated by Robots (PICMOR), and the control group, who joined in a control program based on unstructured free conversations. Furthermore, regions whose volume was positively correlated with an increase in verbal fluency task scores throughout the intervention period were explored.ResultsResults showed that the volume of several regions, including the superior frontal gyrus, parahippocampal gyrus/hippocampus, posterior middle temporal gyrus, and postcentral gyrus, was greater in the intervention group than in the control group. In contrast, no regions showed greater volume in the control group than in the intervention group. The region whose volume showed a positive correlation with the increased task scores was identified in the inferior parietal lobule.ConclusionsAlthough definitive conclusions cannot be drawn from this study due to a lack of MRI data from the pre-intervention period, it achieved the exploratory purpose by successfully identifying candidate brain regions that reflect the beneficial effect of conversation-based interventions on cognitive function, including the lateral prefrontal cortex, which plays an important role in executive functions.Trial registrationThe trial was retrospectively registered on 7 May 2019 (UMIN Clinical Trials Registry number: UMIN000036667).

Older Victims of Mass Marketing Scams: An Analysis of Data Seized From Scammers

Mass marketing scams are some of the most common frauds in America, and include scams perpetrated through the mail. A growing body of research indicates that older adults face a greater risk of victimization due to age-related changes in cognitive functioning and social isolation, and may be more likely to fall victim repeatedly. The aim of this study is to determine the frequency of repeat mass marketing fraud (revictimization) among older adults and patterns of victimization associated with age, scam type, seasonality, and geography. We use two decades of non-public administrative data from the United States Postal Inspection Service (USPIS). These databases were seized during law enforcement investigations of mass mailing scam organizations and contain more than 2 million unique U.S. victims and their transactions with four different fraud organizations. Victims were matched across datasets using name, address, and a change of address file. We find that revictimization rates increase with age in psychic scams. The 10,000 victims who responded the most times (between 82 and 562 times) were 78 years old on average and suffered $4,700 in total losses per person. Other significant trends emerged for lottery and sweepstakes scams. Unlike prior fraud victimization studies, inferences on victim characteristics are based on actual victim experiences with fraud rather than hypothetical scenarios or surveys where victims must self-report fraud. Findings provide valuable policy-relevant information regarding older victims and the patterns of chronic victimization.

Interactive effects of age and inflammation on change in ecologically-assessed cognitive functioning

Inflammation has been implicated as a precursor to steeper declines in age-associated cognitive decline. Here we investigated biomarkers of peripheral inflammation [basal cytokines, stimulated cytokines (ex vivo), C-reactive protein (CRP)] as moderators of age-related changes in cognitive functioning. As part of the Effects of Stress on Cognitive Aging, Physiology, and Emotion (ESCAPE) study, participants (N = 233; 65% female; 63% Black, 25% Hispanic; 25-65 years of age) completed up to four instances of ambulatory cognitive testing per day across two weeks, over three waves of annual assessments. After each 2-week ecological momentary assessment (EMA) burst, blood was collected and assayed for inflammatory biomarkers. Performance on spatial working memory (mean Euclidean distance errors), processing speed (mean symbol search reaction time), and working memory (n-back test accuracy) tasks were averaged across all instances within an EMA burst. CRP and age interactively predicted change in spatial working memory (B = 0.003, [0.000, 0.005], t(133.60) = 2.350, p = 0.020) such that higher CRP at older ages (~60 years) was associated with a loss of the expected practice effects across waves; at younger ages, CRP did not relate to change in spatial working memory. In a similar fashion, basal (B = -0.002, [-0.004, -0.000], t(103.26) = -2.399, p = 0.018) and stimulated cytokine levels (B = -0.002, [-0.004, -0.000], t(126.65) = -2.183, p = 0.031) interacted with age to predict change in processing speed across waves. These results indicate that inflammation may be critically associated with changes in cognitive functioning in older mid-life adults.

Exploring awareness of age-related changes among over 50s in the UK: findings from the PROTECT study.

Older people describe positive and negative age-related changes, but we do not know much about what contributes to make them aware of these changes. We used content analysis to categorize participants' written comments and explored the extent to which the identified categories mapped onto theoretical conceptualizations of influences on awareness of age-related change (AARC). Cross-sectional observational study. The study sample comprised 609 UK individuals aged 50 years or over (mean (SD) age = 67.9 (7.6) years), enrolled in the PROTECT study. Between January and March 2019, participants provided demographic information, completed a questionnaire assessing awareness of age-related change (AARC-10 SF), and responded to an open-ended question asking them to comment on their responses. While some of the emerging categories were in line with the existing conceptual framework of AARC (e.g. experiencing negative changes and attitudes toward aging), others were novel (e.g. engagement in purposeful activities or in activities that distract from age-related thoughts). Analysis revealed some of the thought processes involved in selecting responses to the questionnaire items, demonstrating different ways in which people make sense of specific items. Results support the ability of the AARC questionnaire to capture perceived age-related changes in cognitive functioning, physical and mental health, and engagement in social activities and in healthy and adaptive behaviors. However, findings also suggest ways of enriching the theoretical conceptualization of how AARC develops and offer insights into interpretation of responses to measures of AARC.

Effects of a Tea Cultivar "MK5601" on Behaviors and Hippocampal Neurotrophin-3 Levels in Middle-Aged Mice.

Dietary factors are thought to play an important role in the prevention of cognition diseases and depression in late life. In the present study, we compared the effects between the theogallin-rich tea cultivar, "MK5601" and a common Japanese tea cultivar, "Yabukita" on behaviors and hippocampal neurotrophin levels in experimental animals. Middle-aged mice (aged 8 mo) were given either of the tea infusions or water ad libitum for 4 mo. In the novel object location test, the middle-aged mice drinking water or "Yabukita" performed worse than young mice (aged 2-3 mo) although the middle-aged mice drinking "MK5601" retained spatial memory at the same level as the young mice. We also found that the middle-aged mice drinking "MK5601" showed high levels of neurotrophin-3 in the hippocampus. In conclusion, the "MK5601" tea infusion appears to be effective in preventing age-related changes in cognitive function, as compared with a common Japanese tea cultivar.

Contemporary Approaches to the Study of Cognitive Aging

Cognitive aging research is gaining societal and practical importance because of population aging. Current research is focused on describing age differences and age-related changes in cognitive performance, understanding potential causes underlying these differences and changes, and identifying factors that promote maintenance of cognitive functioning in old age. The goal of this research group is to showcase new developments in research studying age differences in cognitive performance and longitudinal cognitive change in the second half of life. Hülür et al. examine associations between midlife occupational factors and trajectories of cognitive change using data from the German Interdisciplinary Longitudinal Study of Adult Development and Aging (ILSE). Luo et al. use 12-year longitudinal data from 499 older participants in ILSE to study bidirectional associations between social relationships and cognitive performance. Small et al. examine the correspondence between objective and subjective cognitive performance, and measures of fatigue and depressed mood in experience sampling data from breast cancer survivors. Haas et al. compare laboratory and at-home online assessments of cognitive status and prospective memory over the adult lifespan and evaluate the quality of self-administered tests. The discussion by Elizabeth Stine-Morrow will focus on how these approaches contribute to our understanding of processes of cognitive aging and how they can be utilized to promote maintenance of cognitive functioning in old age.

The impact of cognitive functioning on driving performance of older persons in comparison to younger age groups: A systematic review

Older drivers are at a severely higher risk for motor vehicle crash involvement. Due to the global aging of the population, this increased crash risk has a significant impact on society, as well as on an older individual’s quality of life. For this reason, there is a need for understanding how normal age-related changes in cognition and underlying brain dynamics impact driving performance to identify the functional and neurophysiological biomarkers that could be used to design strategies to preserve or improve safe driving behavior in older persons. This review provides an overview of the literature on age-related changes in cognitive functioning and brain dynamics that impact driving simulator performance of healthy persons. A systematic literature search spanning the last ten years was conducted, resulting in 22 eligible studies. Results indicated that various aspects of cognition, most importantly executive function, complex attention, and dual tasking, were associated with driving performance, irrespective of age. However, there was a distinct age-related decline in cognitive and driving performance. Older persons had a more variable, less consistent driving simulator performance, such as more variable speed adaptation or less consistent lane keeping behavior. Only a limited number of studies evaluated the underlying brain dynamics in driving performance. Therefore, future studies should focus on implementing neuroimaging techniques to further unravel the neural correlates of driving performance.

Reduced Retinal Thickness Predicts Age-Related Changes in Cognitive Function.

Currently, there is a lack of biomarkers to identify individuals in the early stages of Alzheimer’s disease (AD). A preponderance of evidence suggests that neurodegenerative processes that affect the brain, may also affect the retina. Using optical coherence tomography (OCT), a non-invasive approach, many have shown thinning of the retina in AD and the developmental precursor to AD, mild cognitive impairment (MCI). However, the relationship between retinal thickness and cognitive function is not entirely clear. This is likely due to the disparity in diagnostic criteria used to determine MCI that does not fully probe the cognitive domains that are particularly vulnerable to aging. This study used a comprehensive neuropsychological assessment involving multiple domains of cognition to determine if retinal thickness correlates with cognitive performance in a normal aged population. In this study, 20 healthy individuals between 60 and 90 years of age were administered neuropsychological assessments probing various domains of cognitive function, and OCT to measure peripapillary retinal nerve fiber layer (RNFL) thickness. We found that RNFL thickness is correlated with neuropsychological performance in multiple cognitive domains (e.g., working memory, psychomotor speed, and executive function). Our work demonstrates a positive correlation between RNFL thickness and several, but not all, domains of cognitive function in a normative aging population. By determining which cognitive domains retinal thickness can predict, this work can help identify individuals at risk or in preclinical stages of AD and other neurodegenerative diseases.

PARASYMPATHETIC INFLUENCE ON COGNITIVE AGING IS MODERATED BY SYMPATHETIC ACTIVITY, ESPECIALLY IN EARLY MIDLIFE

The two branches of the autonomic nervous system (ANS) have been individually linked to age-related changes in cognitive functioning: The parasympathetic nervous system (PNS) is thought to support healthy cognitive aging, whereas the sympathetic nervous system (SNS) has been linked to heightened cognitive decline. Despite these separate findings and despite the integrative nature of the ANS, little work has examined the two branches simultaneously to better understand their interactive effects on age-related cognitive changes. We examined cognitive change in two waves of the MIDUS cognitive project and indexed PNS and SNS activity from heart rate variability and epinephrine levels (respectively) from the MIDUS biomarker project (n = 764, 56% female, mean age = 54.1 years). Our findings indicate that higher PNS levels attenuate cognitive decline, but only among individuals with low SNS levels; at higher SNS levels, the beneficial effects of the PNS are blocked. Further, lower PNS levels can be somewhat compensated for by increased SNS levels. This pattern was most robust among individuals transitioning to mid-life (i.e., 35-40 years old at the initial cognitive test). These results suggest that interventions targeting the ANS as a modifiable factor in cognitive aging should consider both ANS branch’s effects simultaneously, particularly in the early stages of midlife.

The 5-HTTLPR Polymorphism of the Serotonin Transporter Gene and the Intellectual Environment of Work Activity as Factors Associated with Changes to Memory in Aging

The heterogeneity of mental aging is due to the influences of both genetic and environmental factors. Among the latter, an important role is played by intellectual activity. An association was found between the serotonin transporter 5-HTTLPR gene and the efficiency of solving cognitive tasks, and the “adaptive” nature of one of its genotypes provided grounds for studying the associations of this polymorphism with age-related changes in cognitive functions in relation to the intellectual aspect of professional work. The study included young and old scientists (scientific activity, SA, N = 132) and people with no involvement in scientific activity (NSA, N = 157). The efficiency of verbal memory was assessed in terms of reproduction of words from the right and left ears in a dichotic test procedure and recognition of previously presented words; that of imaginal memory was assessed in terms of the recognition of figures. Independently of age, SA subjects had higher measures of verbal memory than NSA. The intellectual aspect of SA was a factor preventing age-related decline in memory for words addressed to the left hemisphere. Independently of other factors, carriers of the S′ (S or LG) alleles of the 5-HTTLPR polymorphism, as compared with carriers of the L′/L′ (LA/La) genotype, demonstrated better measures of imaginal memory. Thus, the initial cognitive potential and cognitive function-stimulating aspect of SA promotes maintenance of the functional activity of the left hemisphere. Measures of right-hemisphere imaginal memory were associated with the genome.

What are the earlier life contributions to reserve and resilience?

The brain's structures and functions arise from a combination of developmental processes and interaction with environmental experiences, beginning in utero and continuing throughout the lifespan. Broadly, the process that we think of as “successful aging” likely has its foundation in early life and is continuously shaped as life experiences are programmed into the brain in response to a changing environment. Thus, individual lifestyle choices and interventions aimed at increasing cognitive reserve and resilience could change the course of cognitive aging. To determine the relative efficacy of these approaches, we will need to understand how the timing of these interventions (e.g., age, duration, frequency) influences cognitive capacity through the lifespan. Although analysis of age-related changes in cognitive function reveals a general decline at the population level, it has become clear that there is great individual variance in the extent to which cognitive function changes with advanced age. The factors responsible for the individual differences in cognitive decline are unclear, but uncovering them with new analytical tools, epigenetic approaches, and subpopulation studies will provide a roadmap toward enhancing reserve and resilience in the population at large and preserving cognitive function in a greater number of aging individuals.

Machine Learning Enhances the Efficiency of Cognitive Screenings for Primary Care

Incorporation of cognitive screening into the busy primary care will require the development of highly efficient screening tools. We report the convergence validity of a very brief, self-administered, computerized assessment protocol against one of the most extensively used, clinician-administered instruments-the Montreal Cognitive Assessment (MoCA). Two hundred six participants (mean age = 67.44, standard deviation [SD] = 11.63) completed the MoCA and the computerized test. Three machine learning algorithms (ie, Support Vector Machine, Random Forest, and Gradient Boosting Trees) were trained to classify participants according to the clinical cutoff score of the MoCA (ie, < 26) from participant performance on 25 features of the computerized test. Analysis employed Synthetic Minority Oversampling TEchnic to correct the sample for class imbalance. Gradient Boosting Trees achieved the highest performance (accuracy = 0.81, specificity = 0.88, sensitivity = 0.74, F1 score = 0.79, and area under the curve = 0.81). A subsequent K-means clustering of the prediction features yielded 3 categories that corresponded to the unimpaired (mean = 26.98, SD = 2.35), mildly impaired (mean = 23.58, SD = 3.19), and moderately impaired (mean = 17.24, SD = 4.23) ranges of MoCA score ( F = 222.36, P < .00). In addition, compared to the MoCA, the computerized test correlated more strongly with age in unimpaired participants (ie, MoCA ≥26, n = 165), suggesting greater sensitivity to age-related changes in cognitive functioning. Future studies should examine ways to improve the sensitivity of the computerized test by expanding the cognitive domains it measures without compromising its efficiency.