Why education is linked to higher cognitive function in aging is fiercely debated. Leading theories propose that education reduces brain decline in aging, enhances tolerance to brain pathology, or that it does not affect cognitive decline but rather reflects higher early-life cognitive function. To test these theories, we analyzed 407.356 episodic memory scores from 170.795 participants > 50 years, alongside 15.157 brain MRIs from 6.472 participants across 33 Western countries. More education was associated with better memory, larger intracranial volume and slightly larger volume of memory-sensitive brain regions. However, education did not protect against age-related decline or weakened effects of brain decline on cognition. The most parsimonious explanation for the results is that the associations reflect factors present early in life, including propensity of individuals with certain traits to pursue more education. While education has numerous benefits, the notion that it provides protection against cognitive or brain decline is not supported.

Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II (nmin = 328; nmax = 1 517, women = 51%; 14.27 years of education), we examined how levels and 7-year changes in indicators derived from blood assays, magnetic resonance imaging brain scans, other-ratings, and self-reports converge among older adults. We included 8 epigenetic biomarkers (incl. 5 epigenetic "clocks"), a BioAge composite from clinical laboratory parameters, brain age, skin age, subjective age, subjective life expectancy, and subjective health horizon. We found moderate associations within aging domains, both cross-sectionally and longitudinally over 7 years. However, associations across different domains were infrequent and modest. Notably, participants with older BioAge had correspondingly older epigenetic ages. Our results suggest that different aging clocks are only loosely interconnected and that more specific measures are needed to differentiate healthy from unhealthy aging.

ABSTRACT INTRODUCTION Given the established association between DNA methylation and the pathophysiology of dementia and its plausible role as a molecular mediator of lifestyle and environment, blood-derived DNA methylation data could enable early detection of dementia risk. METHODS In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in two independent cohorts of Alzheimer’s disease (AD) and Parkinson’s disease (PD). RESULTS We established a multivariate methylation risk score (MMRS) to identify the status of mild cognitive impairment (MCI) cross-sectionally, independent of age and sex. We further demonstrated significant predictive capability of this score for the prospective onset of cognitive decline in AD and PD. DISCUSSION Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk.

Research across a number of different areas in psychology has long shown that optimism and pessimism are predictive of a number of important future life outcomes. Despite a vast literature on the correlates and consequences, we know very little about how optimism and pessimism change across adulthood and old age and the sociodemographic factors that are associated with individual differences in such trajectories. In the present study, we conducted (parallel) analyses of standard items from the Life Orientation Test (Scheier & Carver, 1985) in three comprehensive data sets: Two-wave data from both the Berlin Aging Study II (N = 1,423, aged 60-88; M = 70.4, SD = 3.70) and the Midlife in the U.S. Study (N = 1,810 aged 60-84; M = 69.12, SD = 6.47) as well as cross-sectional data from the Survey of Health, Aging, and Retirement (N = 17,087, aged 60-99; M = 70.19, SD = 7.53). Using latent change-regression models and locally weighted smoothing curves revealed that optimism is on average very stable after age 60, with some evidence in Survey of Health, Aging, and Retirement of lowered optimism in very old age. Consistent across the three independent studies, pessimism evinced on average modest increases, ranging between .25 and .50 SD per 10 years of age. Of the sociodemographic factors examined, higher levels of education revealed the most consistent associations with lower pessimism, whereas gender evinced more study-specific findings. We take our results to demonstrate that age-related trajectories and correlates thereof differ for optimism and pessimism. Older adults appear to preserve into older ages those levels of optimistic expectations they have had at 60 years of age and show only modest increases in pessimism. We discuss possible reasons for these findings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ObjectivesChange in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. In this study we describe the body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures.DesignProspective cohort study with three follow-up examinations over the course of 10 years.Setting and ParticipantsIn this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline).MeasurementsBody weight was assessed at four time points. Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared.ResultsOn average, women and men lost 0.87% (n = 227) and 0.5% (n = 245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p < 0.05, n = 245).ConclusionDuring the COVID-19 pandemic, older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.

The tendency of falsely remembering events that did not happen in the past increases with age. This is particularly evident in cases in which features presented at study are re-presented at test in a recombined constellation (termed rearranged pairs). Interestingly, older adults also express high confidence in such false memories, a tendency that may indicate reduced metacognitive efficiency. Within an existing cohort study, we aimed at investigating age-related differences in memory metacognitive efficiency (as measured by meta d' ratio) in a sample of 1522 older adults and 397 young adults. The analysis showed an age-related deficit in metacognition which was more pronounced for rearranged pairs than for new pairs. We then explored associations between cortical thickness and memory metacognitive efficiency for rearranged pairs in a subsample of 231 older adults. By using partial least square analysis, we found that a multivariate profile composed by ventromedial prefrontal cortex, insula, and parahippocampal cortex was uniquely associated with between-person differences in memory metacognitive efficiency. These results suggest that the impairment in memory metacognitive efficiency for false alarms is a distinct age-related deficit, above and beyond a general age-related decline in memory discrimination, and that it is associated with brain regions involved in metacognitive processes.

Abstract Low body weight and especially unwanted weight loss were shown to be associated with higher mortality in older adults. Change in body weight was reported to be one of the unintended side effects of lockdown measures that were put in place to combat the COVID-19 pandemic. In this study, we first describe weight change in 472 participants (mean age: 67.5 years, 48% women) of the Berlin Aging Study-II (BASE-II) that was collected at four timepoints over an average total follow-up time of 10 years. In a second step we examine differences in weight change between groups defined by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological aging markers (epigenetic clocks, telomere length), and frailty. During the follow-up period, which includes the first six months of the pandemic, women and men lost on average 0.87% and 0.5% of their body weight per year. A statistically significantly higher rate of weight loss was detected for men with low positive affect, accelerated epigenetic age (7-CpG clock), diagnosed metabolic syndrome as well as a more masculine gender score (all p< 0.05). Although the literature generally suggests an increase in body weight during the pandemic, older participants of the BASE-II sample lost 2.5-times (women) and 2-times (men) more weight than expected in this age group. Our explorative analysis of additional variables assessed during an examination directly before the pandemic’s onset could inform future studies that aim at a more in depth understanding of the matter.

To check claims of a "loneliness epidemic," we examined whether current cohorts of older adults report higher levels and/or steeper age-related increases in loneliness than earlier-born peers. Specifically, we used 1,068 age-matched longitudinal reports (M-age observations = 79 years, 49% women) of loneliness provided by independent samples recruited in the German city of Berlin in 1990 and 2010, n = 257 participants in the Berlin Aging Study (BASE) and n = 383 participants in Berlin Aging Study II (BASE-II). Using multilevel models that orthogonalize between-person and within-person age effects, we examined how responses to items from the UCLA Loneliness Scale provided by observation-matched cohorts differed with age and across cohorts, and if those differences might be explained by a variety of individual factors. Results revealed that at age 79, the later-born BASE-II cohort reported substantially lower levels of loneliness than the earlier-born BASE cohort (d = -0.84), with cohort differences accounting for more than 14% of the variance in loneliness. Age trajectories, however, were parallel without evidence of cohort differences in rates of within-person age-related changes in loneliness. Differences in gender, education, cognitive functioning, and external control beliefs accounted for the lion's share of cohort-related differences in levels of loneliness. Results show that loneliness among older adults has shifted to markedly lower levels today, but the rate at which loneliness increases with age proceeds similarly as 2 decades ago. Future studies should investigate how psychosocial functioning across the life course is progressing in different sociohistorical contexts and in other age groups, such as younger and middle-aged adults.

According to the maintenance hypothesis (Nyberg et al., 2012), structural integrity of the brain’s grey matter helps to preserve cognitive functioning into old age. A corollary of this hypothesis that can be tested in cross-sectional data is that grey-matter structural integrity and general cognitive ability are positively associated in old age. Building on Köhncke et al. (2021), who found that region-specific latent factors of grey-matter integrity are positively associated with episodic memory ability among older adults, we examine associations between general factors of grey-matter integrity and a general factor of cognitive ability in a cross-sectional sample of 1466 participants aged 60–88 years, 319 of whom contributed imaging data. Indicator variables based on T1-weighted images (voxel-based morphometry, VBM), magnetization-transfer imaging (MT), and diffusion tensor imaging-derived mean diffusivity (MD) had sufficient portions of variance in common to establish latent factors of grey-matter structure for a comprehensive set of regions of interest (ROI). Individual differences in grey-matter factors were positively correlated across neocortical and limbic areas, allowing for the definition of second-order, general factors for neocortical and limbic ROI, respectively. Both general grey-matter factors were positively correlated with general cognitive ability. For the basal ganglia, the three modality-specific indicators showed heterogenous loading patterns, and no reliable associations of the general grey-matter factor to general cognitive ability were found. To provide more direct tests of the maintenance hypothesis, we recommend applying the present structural modeling approach to longitudinal data, thereby enhancing the physiological validity of latent constructs of brain structure.

BACKGROUND AND OBJECTIVE:It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus-Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer's disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC signal intensity 2) whether LC mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test - TMT), and 3) whether LC signal intensity relates to an objective measure of brain maintenance (BrainPAD). METHODS:The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC signal intensity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA - measured with Food Frequency Questionnaire - FFQ). As a control procedure, the same analyses were repeated on other main seeds of the neuromodulators' subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. RESULTS:Results show that HD-Tyr-IDA is positively associated with LC signal intensity. Similarly, LC disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. CONCLUSIONS:These findings provide the first evidence linking tyrosine intake with LC-NA system signal intensity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Physical activity (PA) has a substantial impact on health and mortality. Besides questionnaires that rely on subjective assessment of activity levels, accelerometers can help to objectify an individual’s PA. In this study, variables estimating PA and sleep time obtained through the wGT3X-BT activity monitor (ActiGraph LLC, USA) in 797 participants of the Berlin Aging Study II (BASE-II) were analyzed. Self-reports of PA and sleep time were recorded with Rapid Assessment of Physical Activity (RAPA) and the Pittsburgh Sleep Quality Index sleep questionnaire (PSQI). Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), fasting glucose, and hemoglobin A1c (HbA1c) were determined in an accredited standard laboratory. Of all participants, 760 fulfilled the PA wear-time criteria. In this sample mean age was 75.6 years (SD: 3.8 years, range 66.0–94.1 years) and 53% of the included participants were women. Average wear time was 23.2 h/day (SD 1.3 h/day). Statistically significant differences between RAPA groups were found for all accelerometric variables except energy expenditure. Post-hoc analysis, however, suggested low agreement between subjective and device-based assessment of physical activity. TC, HDL-C, LDL-C, TG, fasting glucose and HbA1c were weakly correlated with accelerometric variables (Pearson’s r ≤ 0.25). Device-based average sleep time per night (mean sleep time = 6.91 h, SD = 1.3, n = 720) and self-reported average sleep time per night (mean sleep time = 7.1 h, SD = 1.15 h, n = 410) were in a comparable range and moderately correlated (Pearson’s r = 0.31, p < 0.001, n = 410). Results from this study suggest that self-reported PA obtained through the RAPA and device-based measures assessed by accelerometers are partially inconsistent in terms of the physical activity level of the participants. Self-reported and device-based measures of average sleep time per night, however, were comparable.

Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, starts accumulating in the locus coeruleus (LC), the brain’s major noradrenaline supply, during the first decades of life. Facilitated by technical advances, recent evidence shows that age-related deficits in noradrenergic neuromodulation impinge on late-life memory. However, investigations assessing longitudinal locus coeruleus changes and their association with senescent memory are scarce. Moreover, comparisons to other neuromodulatory systems that decline with age are lacking, questioning the specificity of noradrenergic effects. We collected high-resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area (SN–VTA) and the noradrenergic locus coeruleus (LC) of 320 younger and older participants of the Berlin Aging Study-II at two time points (TP1, TP2; ∼1.9 years apart). The imaging protocol included three dedicated scans sensitive to the SN–VTA and LC. We aggregated the information shared across imaging modalities by estimating multimodal latent factors expressing dopaminergic and noradrenergic integrity. Participants also completed a comprehensive cognitive battery at three time points (TP1–TP3), including tests of fluid intelligence, episodic memory, and working memory. We used structural equation modeling to evaluate cross-sectional associations of SN–VTA and LC integrity with late-life cognition. In a second set of models, we probed longitudinal changes in SN–VTA and LC integrity (TP1–TP2) and used them to predict participants’ future cognitive performance (TP3). Cross-sectionally, we found differential associations of dopaminergic and noradrenergic nuclei with late-life cognition. While LC integrity was positively related to better episodic memory across several memory tasks, SN–VTA integrity was positively related to working memory performance. Moreover, consistent with a largely shared biosynthesis of the neuromodulators, dopaminergic and noradrenergic nuclei correlated positively. Longitudinally, we found that older age was associated with more negative change in SN–VTA and LC integrity (TP1–TP2). Importantly, more negative changes in LC integrity reliably predicted worse future episodic memory (at TP3). These findings support the feasibility of in-vivo indices for catecholaminergic integrity with potential clinical utility, given the degeneration of both neuromodulatory systems in several age-associated diseases. Moreover, they highlight differential roles of dopaminergic and noradrenergic neuromodulatory nuclei in late-life cognitive decline.

Abstract Objectives Throughout 2021, the coronavirus disease (COVID-19) pandemic caused renewed restrictions across Germany. Given the growing evidence that the pandemic negatively affects older adults’ health and well-being, this study investigated health sensitivity (emotional reactions to momentary health challenges) and its moderators (age, morbidity, perceived COVID-19 risks and worries) among older adults in their everyday lives during the second and third waves of the pandemic. Methods Multilevel models were applied to self-reported momentary health and affect data, collected 6 times per day across 7 consecutive days in 104 participants (Mage = 76.35; range: 67–88 years), assessed between April and June 2021 (~300,000 COVID-19 cases in Germany at the time). Results Health sensitivity was unrelated to age and lower with higher morbidity. Importantly, older adults showed higher health sensitivity in moments when they also perceived a greater risk of contracting COVID-19. Discussion Findings suggest that sociocontextual factors related to the pandemic modulate emotional reactions to momentary health challenges, thereby underscoring the consequences of COVID-19 for older adults’ emotional experiences.

DNA methylation (DNAm) is an epigenetic mark with essential roles in disease development and predisposition. Here, we created genome-wide maps of methylation quantitative trait loci (meQTL) in three peripheral tissues and used Mendelian randomization (MR) analyses to assess the potential causal relationships between DNAm and risk for two common neurodegenerative disorders, i.e. Alzheimer's disease (AD) and Parkinson's disease (PD). Genome-wide single nucleotide polymorphism (SNP; ~5.5M sites) and DNAm (~850K CpG sites) data were generated from whole blood (n=1,058), buccal (n=1,527) and saliva (n=837) specimens. We identified between 11 and 15 million genome-wide significant (p<10-14) SNP-CpG associations in each tissue. Combining these meQTL GWAS results with recent AD/PD GWAS summary statistics by MR strongly suggests that the previously described associations between PSMC3, PICALM, and TSPAN14 and AD may be founded on differential DNAm in or near these genes. In addition, there is strong, albeit less unequivocal, support for causal links between DNAm at PRDM7 in AD as well as at KANSL1/MAPT in AD and PD. Our study adds valuable insights on AD/PD pathogenesis by combining two high-resolution "omics" domains, and the meQTL data shared along with this publication will allow like-minded analyses in other diseases.

History-graded increases in older adults' levels of cognitive performance are well documented, but little is known about historical shifts in within-person change: cognitive decline and onset of decline. We combined harmonized perceptual-motor speed data from independent samples recruited in 1990 and 2010 to obtain 2,008 age-matched longitudinal observations (M = 78 years, 50% women) from 228 participants in the Berlin Aging Study (BASE) and 583 participants in the Berlin Aging Study II (BASE-II). We used nonlinear growth models that orthogonalized within- and between-person age effects and controlled for retest effects. At age 78, the later-born BASE-II cohort substantially outperformed the earlier-born BASE cohort (d = 1.20; 25 years of age difference). Age trajectories, however, were parallel, and there was no evidence of cohort differences in the amount or rate of decline and the onset of decline. Cognitive functioning has shifted to higher levels, but cognitive decline in old age appears to proceed similarly as it did two decades ago.

It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

Urbanization is Globally increasing at a rapid rate but its consequences for mental health, including cognitive functioning, are not well understood. In particular, little is known about the effects of different morphological features associated with urban development, such as variations in the densities of urban fabric (i.e., degrees of ground sealing). We investigated associations of episodic memory, working memory, and fluid intelligence with different densities of urban fabric, obtained from the European Urban Atlas, in a structural equation model framework. We used data on 1053 healthy participants aged 61-88 years (mean age 70.33; SD = 3.75; 51% female) drawn from the Berlin Aging Study II. All participants were living within the city of Berlin, Germany. Our data include the precise geographical coordinates of every household, thereby permitting the calculation of the share of each density type of urban fabric within a 1-km radius around the household. We found these types to be significantly related to working memory and fluid intelligence. No significant association emerged for episodic memory. All results were robust against the inclusion of a set of covariates known to be related to cognitive performance. We discuss the idea of enrichment effects due to morphological features of urban development as one possible mechanism.

Changes in dopaminergic neuromodulation play a key role in adult memory decline. Recent research has also implicated noradrenaline in shaping late-life memory. However, it is unclear whether these two neuromodulators have distinct roles in age-related cognitive changes. Here, combining longitudinal MRI of the dopaminergic substantia nigra–ventral tegmental area (SN-VTA) and noradrenergic locus coeruleus (LC) in younger ( n = 69) and older ( n = 251) adults, we found that dopaminergic and noradrenergic integrity are differentially associated with memory performance. While LC integrity was related to better episodic memory across several tasks, SN-VTA integrity was linked to working memory. Longitudinally, we found that older age was associated with more negative change in SN-VTA and LC integrity. Notably, changes in LC integrity reliably predicted future episodic memory. These differential associations of dopaminergic and noradrenergic nuclei with late-life cognitive decline have potential clinical utility, given their degeneration in several age-associated diseases.

White matter integrity and cognition have been found to decline with advancing adult age. Aerobic exercise may be effective in counteracting these declines. Generally, white matter integrity has been quantified using a volumetric measure (WMV) and with tensor-based parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), the validity of which appears to be compromised in the presence of crossing fibers. Fixel-based analysis techniques claim to overcome this problem by yielding estimates of fiber density (FD), cross-section (FC), and their product (FDC) in multiple directions per voxel. In a sample of 61 healthy older adults (63–76 years old), we quantified changes in white matter integrity following an aerobic exercise intervention with the commonly used volumetric and tensor-based metrics (WMV, FA, MD) and with fixel-based metrics (FD, FC, FDC). We investigated the associations of changes in these white matter parameters with changes in cardiovascular fitness and Digit Symbol Substitution task (DSST) performance, a marker of perceptual speed. In line with previous findings, we observed maintained WMV in the corpus callosum of exercisers, and positive change-change correlations between WMV and fitness, and between WMV and perceptual speed. For FA and MD, group differences in change opposite to those hypothesized were found in the corpus callosum, posterior corona radiata, and superior longitudinal fasciculus at an uncorrected significance threshold. Likewise, regions in superficial WM in the prefrontal cortex showed group differences in FD and FDC change, uncorrected, with more positive change in controls and more negative change in exercisers. Finally, changes in FD and FDC were found to be inversely correlated to changes in fitness and DSST performance. The present results corroborate previous findings of WMV changes, but cast doubt on current physiological interpretations of both tensor-based and fixel-based indicators of white matter properties in the context of exercise intervention studies.