Role of intergenerational connections in cognitive aging: Evidence from a Chinese longitudinal study.

Objective: To explore the impact of intergenerational connections on cognitive function in middle-aged and older adults (45-60 years and over 60 years, respectively) and analyze the urban-rural and sex differences in the effects of intergenerational connections on cognitive function. Method: Based on China Health and Retirement Longitudinal Study data (CHARLS), this study conducted ID matching for four waves of data from 2011, 2013, 2015, and 2018. Cognitive function was measured via Telephone Interview for Cognitive Status-modified (TICS-m), word recall, and imitation drawing. Using a combination of cross-sectional and longitudinal research, we constructed the cross-lagged panel model (CLPM) with a sample of 1,480 participants to explore the relationship between intergenerational connections and cognitive function. Results: This study examines the impact of intergenerational connections on cognitive function in middle-aged (45-60 years) and older adults (over 60 years) using data from the CHARLS. It identifies urban-rural and sex differences, with notable effects among rural female participants. The frequency of meeting with one child negatively predicts cognitive function (ß = -0.040, p = 0.041), and the frequency of communication with one child positively predicts cognitive function (ß = 0.102, 0.068, 0.041, p < 0.001, p = 0.001, 0.045). Meanwhile, intergenerational connections with multiple children positively predicts cognitive function (ß = 0.044, p = 0.031), (ß = 0.128, 0.084, and 0.056, p < 0.001, 0.001, p = 0.008). There are urban-rural and sex differences in the effects of intergenerational connections on cognitive function; additionally, the effects of intergenerational connections on cognitive function are significant in rural female middle-aged and older adults. Discussion: This study proposes the theory of skewed intergenerational support, which suggests that as middle-aged and older adults age, the responsibility for intergenerational support is skewed toward one child. This leads to conflicts between middle-aged and older parents and the child, which further affects cognitive function. In addition, this study put forward the boat-carrying theory of intergenerational relations and "to hold a bowl of water level" is the art of dealing with intergenerational relationships.

Predicting brain atrophy and cognitive aging trajectories with baseline subjective cognitive concerns in cognitively normal older adults.

Subjective cognitive concerns (SCC) are common even in cognitively normal older adults who lack objectively-detectable deficits on standard neuropsychological evaluation. The clinical relevance of these concerns, particularly considering the nature of concerns (e.g., memory versus non-memory), remains unclear. Thus, we examined whether baseline memory and non-memory SCC relate to longitudinal change in brain volume and neuropsychological test performance in 476 functionally-intact, objectively unimpaired older adults (Mage = 72y, 56 % female, follow-up time = 1 - 9 years). Mixed-effects models revealed that both higher baseline memory and non-memory SCC predicted greater atrophy in total gray matter and dorsolateral prefrontal cortex atrophy over time, while only memory SCC predicted steeper medial temporal lobe atrophy. Regarding neuropsychological performance, higher non-memory SCC predicted decline in processing speed performance, while memory SCC did not predict neuropsychological trajectories. SCC are a risk factor for more adverse brain and cognitive aging trajectories, even in functionally-intact, seemingly cognitively normal older adults.

Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders.

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.

National Institute on Aging's 50th Anniversary: Advancing Cognitive Aging Research and the Cognitive Health of Older Adults.

In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults.

The memory binding test in a longitudinal study of cognitive aging and preclinical disease.

OBJECTIVE: The Memory Binding Test (MBT) shows promise in detecting early cognitive changes associated with Alzheimer's disease (AD). This study assesses the psychometric properties (i.e., construct and criterion validity, test-retest reliability) of the MBT and its sensitivity to incipient disease and incident cognitive impairment. METHOD: One hundred forty-nine cognitively unimpaired adults ages 45-85 completed the MBT and neuropsychological tests at baseline; 132 returned for 2-year follow-up. Based on neuroradiological ratings of amyloid positron emission tomography and MRI markers at baseline, they were categorized as healthy (n = 94) or having preclinical disease (n = 55, either on the AD continuum or having non-AD pathologic change). Construct validity was assessed by the associations between MBT scores, demographics, and neuropsychological scores within the healthy group. Criterion validity was assessed by testing how MBT scores correlate with AD biomarkers, differ and discriminate between groups at baseline, and predict incident cognitive impairment. RESULTS: MBT scores decreased with age and were strongly associated with memory and global cognition. MBT scores were largely not associated with amyloid, hippocampal volume, or AD signature cortical volume but related to white matter lesion volume in those with preclinical disease. The preclinical groups performed worse on MBT immediate free recall at baseline than the healthy group, but no scores predicted incident cognitive impairment at follow-up. Most scores demonstrated modest test-retest reliability. CONCLUSIONS: This study demonstrates that the MBT has adequate construct validity in cognitively unimpaired adults, moderate sensitivity to preclinical disease cross-sectionally, and limited prognostic utility. Careful consideration of demographic influences on score interpretation remains necessary. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adult Child Financial Disadvantage and the Cognitive Trajectories Among Older Parents in the United States.

OBJECTIVES: Adult child socioeconomic status (SES) has been identified as a predictor of older parents' cognitive aging. However, studies have primarily relied on educational attainment as the sole measure of adult child SES. We evaluated the relationship between adult children's financial disadvantage and cognitive outcomes of older parents in the United States. METHODS: We used data from U.S. Health and Retirement Study (2000-2014, n = 15,053 respondents ≥51 years with at least 1 adult child). Adult child financial disadvantage was measured with 3 indicators of extremely low income, unemployment, and lack of homeownership. We used linear mixed models to estimate the association between adult child financial disadvantage and the rate of decline in verbal memory scores, controlling for respondents' sociodemographic characteristics. RESULTS: Having at least 1 adult child (vs no adult children) with extremely low income was found to be associated with lower verbal memory (b = -0.041, 95% confidence interval [CI]: -0.043, -0.039) at baseline. There was a small but significant association with the rate of decline in verbal memory z-scores (b = 0.004, 95% CI: 0.000, 0.008) and some evidence of heterogeneity by parent gender, marital status, and SES. DISCUSSION: Offspring financial disadvantage may be influential for older parents' initial level of memory function, although evidence of associations with memory decline was weak. Public policy interventions aimed at improving the economic conditions of adult children may indirectly benefit the cognitive performance of disadvantaged parents in their later life.

Dissociation of focal and large-scale inhibitory functions in the older adults: A multimodal MRI study.

BACKGROUND: The decline of inhibitory in cognitive aging is linked to reduced cognitive and mental capacities in older adults. However, this decline often shows inconsistent clinical presentations, suggesting varied impacts on different inhibition-related tasks. Inhibitory control, a multifaceted construct, involves various types of inhibition. Understanding these components is crucial for comprehending how aging affects inhibitory functions. Our research investigates the influences of aging on large-scale and focal-scale inhibitory and examines the relationship with brain markers. METHODS: We examined the impact of aging on inhibitory in 18 younger (20-35 years) and 17 older adults (65-85 years) using focal and large-scale inhibition tasks. The Gabor task assessed focal-scale inhibition, while the Stop Signal Task (SST) evaluated large-scale inhibition. Participants underwent neuropsychological assessments and MRI scans, including magnetic resonance spectroscopy (MRS) and structural and resting fMRI. RESULTS: Older adults exhibited a marked decline in inhibitory function, with slower SST responses indicating compromised large-scale inhibition. Conversely, the Gabor task showed no significant age-related changes. MRS findings revealed decreased levels of GABA, glutamate, glutamine, and NAA in the pre-SMA, correlating with observed large-scale inhibition in older adults. Additionally, pre-SMA seed-based functional connectivity analysis showed reduced brain network connections in older adults, potentially contributing to inhibitory control deficits. CONCLUSIONS: Our study elucidates the differential effects of aging on inhibitory functions. While large-scale inhibition is more vulnerable to aging, focal-scale inhibition is relatively preserved. These findings highlight the importance of targeted cognitive interventions and underscore the necessity of a multifaceted approach in aging research.

Disparate trajectories of cognitive aging among American Indian and Alaskan Native people with and without HIV.

OBJECTIVE: This study describes trajectories of cognitive aging among American Indian/Alaskan Native (AI/AN) adults with and without HIV and the role of immunosenescence longitudinally. METHOD: We characterized trajectories of cognitive aging in a sample of 333 AI/AN and 309 non-Hispanic White (NHW) adults who were followed longitudinally for up to 20 years by the HIV Neurobehavioral Research Program (HNRP) across six U.S. research sites. We used growth curve modeling with autoregressive Lag-1 structures and heterogeneous residual variances to assess the role of ethnoracial identity and HIV grouping upon decline in trajectories of cognitive aging. RESULTS: HIV- AI/AN adults demonstrated earlier and steeper decline in normative trajectories of cognitive aging on tasks of processing speed, timed tasks of attention/working memory, executive function, and psychomotor speed in comparison to HIV- NHW adults. Accentuated trajectories of cognitive aging were evident in both HIV+ and HIV+ immunosuppressed groups in comparison to HIV- peers and were primarily driven by the role of immunosenescence. CONCLUSIONS: AI/AN disparities in trajectories of cognitive aging are evident and are likely explained by the interplay of biopsychosociocultural factors, including immunosenescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Temporal dynamics of depressive symptoms and cognitive decline in the oldest old: dynamic time warp analysis of the Leiden 85-plus study.

BACKGROUND: The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period. METHODS: Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants). Depressive symptoms were assessed at baseline and at yearly assessments during a follow-up period of up to 5 years, using the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests, including the Mini Mental State Exam, Stroop test, Letter Digit Coding test and immediate and delayed recall. A novel method, dynamic time warping analysis, was employed to model their temporal dynamics within individuals, in undirected and directed time-lag analyses, to ascertain whether depressive symptoms precede cognitive decline in group-level aggregated results or vice versa. RESULTS: The 325 participants were all 85 years of age at baseline; 68% were female, and 45% received intermediate to higher education. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the constituents of cognitive impairment in the oldest old. Of the GDS-15 symptoms, those with the strongest outstrength, indicating changes in these symptoms preceded subsequent changes in other symptoms, were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all P's < 0.01). CONCLUSION: Depressive symptoms preceded cognitive impairment in a population based sample of the oldest old.

The Best of Two Worlds to Promote Healthy Cognitive Aging: Definition and Classification Approach of Hybrid Physical Training Interventions.

A healthy lifestyle can be an important prerequisite to prevent or at least delay the onset of dementia. However, the large number of physically inactive adults underscores the need for developing and evaluating intervention approaches aimed at improving adherence to a physically active lifestyle. In this regard, hybrid physical training, which usually combines center- and home-based physical exercise sessions and has proven successful in rehabilitative settings, could offer a promising approach to preserving cognitive health in the aging population. Despite its potential, research in this area is limited as hybrid physical training interventions have been underused in promoting healthy cognitive aging. Furthermore, the absence of a universally accepted definition or a classification framework for hybrid physical training interventions poses a challenge to future progress in this direction. To address this gap, this article informs the reader about hybrid physical training by providing a definition and classification approach of different types, discussing their specific advantages and disadvantages, and offering recommendations for future research. Specifically, we focus on applying digital technologies to deliver home-based exercises, as their use holds significant potential for reaching underserved and marginalized groups, such as older adults with mobility impairments living in rural areas.

Associations of childhood, adolescence, and midlife cognitive function with DNA methylation age acceleration in midlife.

Prior studies showed increased age acceleration (AgeAccel) is associated with worse cognitive function among old adults. We examine the associations of childhood, adolescence and midlife cognition with AgeAccel based on DNA methylation (DNAm) in midlife. Data are from 359 participants who had cognition measured in childhood and adolescence in the Child Health and Development study, and had cognition, blood based DNAm measured during midlife in the Disparities study. Childhood cognition was measured by Raven's Progressive Matrices and Peabody Picture Vocabulary Test (PPVT). Adolescent cognition was measured only by PPVT. Midlife cognition included Wechsler Test of Adult Reading (WTAR), Verbal Fluency (VF), Digit Symbol (DS). AgeAccel measures including Horvath, Hannum, PhenoAge, GrimAge and DunedinPACE were calculated from DNAm. Linear regressions adjusted for potential confounders were utilized to examine the association between each cognitive measure in relation to each AgeAccel. There are no significant associations between childhood cognition and midlife AgeAccel. A 1-unit increase in adolescent PPVT, which measures crystalized intelligence, is associated with 0.048-year decrease of aging measured by GrimAge and this association is attenuated after adjustment for adult socioeconomic status. Midlife crystalized intelligence measure WTAR is negatively associated with PhenoAge and DunedinPACE, and midlife fluid intelligence measure (DS) is negatively associated with GrimAge, PhenoAge and DunedinPACE. AgeAccel is not associated with VF in midlife. In conclusion, our study showed the potential role of cognitive functions at younger ages in the process of biological aging. We also showed a potential relationship of both crystalized and fluid intelligence with aging acceleration.

Relationship of Self-Reported Physical Activity with Cognition in Middle- Aged Adults.

OBJECTIVE: The increasing prevalence of age-related cognitive decline highlights the importance of physical activity for cognitive health. Regular exercise has been associated with improved mental health and reduced risk of cognitive decline. This study investigated the connection between self-reported physical activity and cognitive function in middle-aged adults. METHODS: This cross-sectional study included 56 Indian adults aged 30-55, selected based on a health screening questionnaire. Participants reported their physical activity using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), which categorized them into low, moderate, and high activity levels. Cognitive functions, including visual memory, executive function, and attention, were assessed using the Cambridge Neuropsychological Automated Testing Battery (CANTAB). Results were statistically analyzed for relationships between cognitive domains and physical activity parameters using Pearson's correlation and linear regression analysis. RESULTS: The study showed a significant positive correlation of attention with moderate and vigorous physical activity, while sedentary behavior negatively impacted attention. Linear regression showed that attention is affected by moderate-intensity activity whereas executive function and visual memory are affected by age. CONCLUSION: This study supports the view that moderate and vigorous intensity activities may positively affect attention in middle-aged adults highlighting the benefits of physical activity.

The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging.

Cognitive decline is a significant health concern in our aging society. Here, we used the model organism C. elegans to investigate the impact of the IIS/FOXO pathway on age-related cognitive decline. The daf-2 Insulin/IGF-1 receptor mutant exhibits a significant extension of learning and memory span with age compared to wild-type worms, an effect that is dependent on the DAF-16 transcription factor. To identify possible mechanisms by which aging daf-2 mutants maintain learning and memory with age while wild-type worms lose neuronal function, we carried out neuron-specific transcriptomic analysis in aged animals. We observed downregulation of neuronal genes and upregulation of transcriptional regulation genes in aging wild-type neurons. By contrast, IIS/FOXO pathway mutants exhibit distinct neuronal transcriptomic alterations in response to cognitive aging, including upregulation of stress response genes and downregulation of specific insulin signaling genes. We tested the roles of significantly transcriptionally-changed genes in regulating cognitive functions, identifying novel regulators of learning and memory. In addition to other mechanistic insights, a comparison of the aged vs young daf-2 neuronal transcriptome revealed that a new set of potentially neuroprotective genes is upregulated; instead of simply mimicking a young state, daf-2 may enhance neuronal resilience to accumulation of harm and take a more active approach to combat aging. These findings suggest a potential mechanism for regulating cognitive function with age and offer insights into novel therapeutic targets for age-related cognitive decline.

Cognitive-Cognitive Dual-task in aging: A cross-sectional online study.

The prevalence of neurodegenerative disorders, particularly dementia, is on the rise across many countries worldwide. This negative trend calls for improving our understanding of cognitive aging. While motor-cognitive dual-task approaches have already been proven valuable for clinical diagnosis, comparatively less research is available on the application of Cognitive-Cognitive Dual-Tasking (CCDT), across several cognitive domains. Moreover, there is limited understanding about how healthy aging affects performance in such dual-tasks in the general population. CCDT entails engaging individuals in multiple cognitive tasks simultaneously and holds promise for remote e-Health interventions. In this cross-sectional study, our objective was to evaluate the suitability of a newly developed, self-administered, online tool for examining age-related differences in memory performance under dual-tasking. 337 healthy adults aged 50-90 underwent a visual memory test (Memo) under both single and dual-task conditions (attend to auditory letters). Additional measures included questionnaires on subjective memory complaints (MAC-Q), on cognitive reserve (CR), and a cognitive screening (auto-GEMS). As expected, the accuracy of visual memory performance exhibited a negative correlation with age and MAC-Q, and a positive correlation with CR and auto-GEMS scores. Dual-tasking significantly impaired performance, and its detrimental effect decreased with increasing age. Furthermore, the protective effect of cognitive reserve diminished with advancing age. These findings suggest that the commonly observed age-related increase in dual-task costs is not universally applicable across all tasks and cognitive domains. With further refinement, a longitudinal implementation of this approach may assist in identifying individuals with a distinct cognitive trajectory and potentially at a higher risk of developing cognitive decline.

Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans.

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.