Deficits in memory metacognitive efficiency in late adulthood are related to distinct brain profile.

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.

Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts.

Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

High-Sensitivity Cardiac Troponin T and Cognitive Decline in Older Adults: Results of the Berlin Aging Study II.

INTRODUCTION: There is evidence of an association between markers of cardiac injury and cognition in patients with cardiovascular disease. We hypothesized that levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with cognitive performance and cognitive decline in a population of predominantly healthy older adults. METHODS: We included 1,226 predominantly healthy adults ≥60 years from the Berlin Aging Study II. Participants were recruited from the general population of the Berlin metropolitan area from 2009 to 2014. At baseline, participants underwent measurement of hs-cTnT and cognitive testing using the extended Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) battery. In addition, the Digit Symbol Substitution Test (DSST) was performed at baseline and at follow-up (7.3 ± 1.4 years after the baseline visit). The CERAD test results were summarized into four cognitive domains (processing speed, executive function, visuo-construction, and memory). After summing-up the respective raw scores, we calculated standardized z scores. We performed unadjusted and adjusted linear regression models to assess links between hs-cTnT and cognitive domains. We used linear mixed models to analyze associations between hs-cTnT and cognitive decline according to changes in DSST scores over time. RESULTS: The mean age of study participants at baseline was 68.5 (±3.6) years, 49% were female, and median hs-cTnT levels were 6 ng/L (IQR 4-8 ng/L). We detected no significant association between hs-cTnT and different cognitive domains at baseline after adjustment for age, sex, education, and cardiovascular risk factors. Hs-cTnT was associated with cognitive decline, which remained statistically significant after full adjustment (adjusted beta-coefficient -0.82 (-1.28 to -0.36), p = 0.001). After stratification for sex, the association with hs-cTnT remained statistically significant in men but not in women. CONCLUSION: Higher hs-cTnT levels in older men are associated with cognitive decline measured with the DSST.

Age differences in diffusivity in the locus coeruleus and its ascending noradrenergic tract.

The noradrenergic locus coeruleus (LC) is a small brainstem nucleus that promotes arousal and attention. Recent studies have examined the microstructural properties of the LC using diffusion-weighted magnetic resonance imaging and found unexpected age-related differences in fractional anisotropy - a measure of white matter integrity. Here, we used two datasets (Berlin Aging Study-II, N = 301, the Leipzig Study for Mind-Body-Emotion Interactions, N = 220), to replicate published findings and expand them by investigating diffusivity in the LC's ascending noradrenergic bundle. In younger adults, LC fractional anisotropy was significantly lower, compared to older adults. However, in the LC's ascending noradrenergic bundle, we observed significantly higher fractional anisotropy in younger adults, relative to older adults. These findings indicate that diffusivity in the LC versus the ascending noradrenergic bundle are both susceptible to structural changes in aging that have opposing effects on fractional anisotropy.

Hippocampal and Parahippocampal Gray Matter Structural Integrity Assessed by Multimodal Imaging Is Associated with Episodic Memory in Old Age.

Maintained structural integrity of hippocampal and cortical gray matter may explain why some older adults show rather preserved episodic memory. However, viable measurement models for estimating individual differences in gray matter structural integrity are lacking; instead, findings rely on fallible single indicators of integrity. Here, we introduce multitrait-multimethod methodology to capture individual differences in gray matter integrity, based on multimodal structural imaging in a large sample of 1522 healthy adults aged 60-88 years from the Berlin Aging Study II, including 333 participants who underwent magnetic resonance imaging. Structural integrity factors expressed the common variance of voxel-based morphometry, mean diffusivity, and magnetization transfer ratio for each of four regions of interest: hippocampus, parahippocampal gyrus, prefrontal cortex, and precuneus. Except for precuneus, the integrity factors correlated with episodic memory. Associations with hippocampal and parahippocampal integrity persisted after controlling for age, sex, and education. Our results support the proposition that episodic memory ability in old age benefits from maintained structural integrity of hippocampus and parahippocampal gyrus. Exploratory follow-up analyses on sex differences showed that this effect is restricted to men. Multimodal factors of structural brain integrity might help to improve our biological understanding of human memory aging.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Location, Location, Location: The Role of Objective Neighborhood Characteristics for Perceptions of Control.

INTRODUCTION: Control beliefs can protect against age-related declines in functioning. It is unclear whether neighborhood characteristics shape how much control people perceive over their life. This article studies associations of neighborhood characteristics with control beliefs of residents of a diverse metropolitan area (Berlin, Germany). METHODS: We combine self-report data about perceptions of control obtained from participants in the Berlin Aging Study II (N = 507, 60-87 years, 51% women) with multisource geo-referenced indicators of neighborhood characteristics using linear regression models. RESULTS: Findings indicate that objective neighborhood characteristics (i.e., unemployment rate) are indeed tied to perceptions of control, in particular, how much control participants feel others have over their lives. Including neighborhood characteristics in part doubled the amount of explained variance compared with a reference model covarying for demographic characteristics only (from R2 = 0.017 to R2 = 0.030 for internal control beliefs; R2 = 0.056 to R2 = 0.102 for external control beliefs in chance; R2 = 0.006 to R2 = 0.030 for external control beliefs in powerful others). DISCUSSION/CONCLUSION: Findings highlight the importance of access to neighborhood resources for control beliefs across old age and can inform interventions to build up neighborhood characteristics which might be especially helpful in residential areas with high unemployment.

A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging.

Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61-80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64-68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.

Hippocampal Subfields and Limbic White Matter Jointly Predict Learning Rate in Older Adults.

Age-related memory impairments have been linked to differences in structural brain parameters, including cerebral white matter (WM) microstructure and hippocampal (HC) volume, but their combined influences are rarely investigated. In a population-based sample of 337 older participants aged 61-82 years (Mage = 69.66, SDage = 3.92 years), we modeled the independent and joint effects of limbic WM microstructure and HC subfield volumes on verbal learning. Participants completed a verbal learning task of recall over five repeated trials and underwent magnetic resonance imaging (MRI), including structural and diffusion scans. We segmented three HC subregions on high-resolution MRI data and sampled mean fractional anisotropy (FA) from bilateral limbic WM tracts identified via deterministic fiber tractography. Using structural equation modeling, we evaluated the associations between learning rate and latent factors representing FA sampled from limbic WM tracts, and HC subfield volumes, and their latent interaction. Results showed limbic WM and the interaction of HC and WM-but not HC volume alone-predicted verbal learning rates. Model decomposition revealed HC volume is only positively associated with learning rate in individuals with higher WM anisotropy. We conclude that the structural characteristics of limbic WM regions and HC volume jointly contribute to verbal learning in older adults.

Future time perspective: Dimensions of opportunities, life, and time are differentially associated with physical health, cognitive functioning, and well-being in old age.

Objective: The present study investigated the multidimensional nature of the future time perspective scale and dimension-specific associations with measures of physical health, cognitive functioning, and well-being.Method: Using data from the Berlin Aging Study II (N = 1,038, M age = 71 years, range = 61-88 years, 52% women), different models of future time perspective were compared using confirmatory factor analyses, and the best-fitting model was then used to explore dimension-specific associations with physical health, cognitive functioning, and well-being measures.Results: A model of future time perspective composed of a focus on opportunities, a focus on life, and a focus on time was found to have the best fit. An extended focus on opportunities was associated with stronger grip strength, more accurate memory, as well as higher life satisfaction and positive affect. An extended focus on time was associated with less accurate memory, lower negative affect, and greater life satisfaction. A focus on life was unrelated to study measures.Discussion: Findings suggest that future time perspective is multidimensional and that these dimensions are differentially associated with physical health, cognitive functioning, and well-being in old age.

Influence of nutritional tyrosine on cognition and functional connectivity in healthy old humans.

Tyrosine is precursor for monoamine neurotransmitters such as dopamine (DA), which is one of the key neurotransmitters in the frontostriatal network and of crucial relevance for mental disorders. Recent research reported that high dose tyrosine application resulted in increased brain DA synthesis, which is consistent with the observation of positive associations between daily tyrosine intake and cognitive test performance. In the present study, we investigated the associations between working memory (WM) dependent tasks and self-reported nutritional tyrosine intake within a large group of healthy elderly humans (286 subjects) by additionally including brain functional data. We observed a negative correlation between tyrosine intake and resting-state functional connectivity (rsFC) between the striatum (putamen) and the prefrontal cortex. That is to say, we found higher rsFC in individuals consuming less tyrosine per day. At the same time, this increasedrsFC or hyperconnectivity was associated with lower WM performance. These findings suggest that lower or insufficient supply of tyrosine might result in dysfunctional connectivity between striatal and frontal regions leading to lower WM capacity in healthy elderly humans.

Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults.

The fact that tyrosine increases dopamine availability that, in turn, may enhance cognitive performance has led to numerous studies on healthy young participants taking tyrosine as a food supplement. As a result of this dietary intervention, participants show performance increases in working memory and executive functions. However, the potential association between habitual dietary tyrosine intake and cognitive performance has not been investigated to date. The present study aims at clarifying the association of episodic memory (EM), working memory (WM) and fluid intelligence (Gf), and tyrosine intake in younger and older adults. To this end, we acquired habitual tyrosine intake (food frequency questionnaire) from 1724 participants of the Berlin Aging Study II (1383 older adults, 341 younger adults) and modelled its relations to cognitive performance assessed in a broad battery of cognitive tasks using structural equation modeling. We observed a significant association between tyrosine intake and the latent factor capturing WM, Gf, and EM in the younger and the older sample. Due to partial strong factorial invariance between age groups for a confirmatory factor analysis on cognitive performance, we were able to compare the relationship between tyrosine and cognition between age groups and found no difference. Above and beyond previous studies on tyrosine food supplementation the present result extend this to a cross-sectional association between habitual tyrosine intake levels in daily nutrition and cognitive performance (WM, Gf, and EM). This corroborates nutritional recommendations that are thus far derived from single-dose administration studies.

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

The Subjective Health Horizon Questionnaire (SHH-Q): Assessing Future Time Perspectives for Facets of an Active Lifestyle.

BACKGROUND: A wider subjective time horizon is assumed to be positively associated with longevity and vitality. In particular, a lifestyle with exposure to novel and varied information is considered beneficial for healthy cognitive aging. At present, measures that specifically assess individuals' perceived temporal extension to engage in active lifestyles in the future are not available. OBJECTIVES: We introduce and validate a new self-report measure, the Subjective Health Horizon Questionnaire (SHH-Q). The SHH-Q assesses individuals' future time perspectives in relation to four interrelated but distinct lifestyle dimensions: (1) novelty-oriented exploration (Novelty), (2) bodily fitness (Body), (3) work goals (Work), and (4) goals in life (Life Goals). The present study aims at: (a) validating the hypothesized factor structure of the SHH-Q, according to which the SHH-Q consists of four interrelated but distinct subscales, and (b) testing the hypothesis that the Novelty and Body subscales of the SHH-Q show positive and selective associations with markers of cognition and somatic health, respectively. METHODS: Using structural equation modeling, we analyzed data from 1,371 healthy individuals (51% women) with a mean age of 70.1 years (SD = 3.6) who participated in the Berlin Aging Study II (BASE-II) and completed the SHH-Q. RESULTS: As predicted, the SHH-Q formed four correlated but distinct subscales: (1) Novelty, (2) Body, (3) Work, and (4) Life Goals. Greater self-reported future novelty orientation was associated with higher current memory performance, and greater future expectations regarding bodily fitness with better current metabolic status. CONCLUSION: The SHH-Q reliably assesses individual differences in four distinct dimensions of future time perspective. Two of these dimensions, Novelty and Body, show differential associations with cognitive status and somatic health. The SHH-Q may serve as a tool to assess how different facets of future time perspective relate to somatic health, cognition, motivation, and affect, and may help to identify the socioeconomic and individual antecedents, correlates, and consequences of an active lifestyle.

Cohort Differences in Psychosocial Function over 20 Years: Current Older Adults Feel Less Lonely and Less Dependent on External Circumstances.

BACKGROUND: Lifespan psychological and life course sociological perspectives indicate that individual development is shaped by social and historical circumstances. Increases in fluid cognitive performance over the last century are well documented and researchers have begun examining historical trends in personality and subjective well-being in old age. Relatively less is known about secular changes in other key components of psychosocial function among older adults. OBJECTIVE: In the present study, we examined cohort differences in key components of psychosocial function, including subjective age, control beliefs, and perceived social integration, as indicated by loneliness and availability of very close others. METHODS: We compared data obtained 20 years apart in the Berlin Aging Study (in 1990-1993) and the Berlin Aging Study II (in 2013-2014) and identified case-matched cohort groups based on age, gender, cohort-normed education, and marital or partner status (n = 153 in each cohort, mean age = 75 years). In follow-up analyses, we controlled for having lived in former East versus West Germany, physical diseases, cohort-normed household income, cognitive performance, and the presence of a religious affiliation. RESULTS: Consistently across analyses, we found that, relative to the earlier-born BASE cohort (year of birth: mean = 1916; SD = 3.38 years; range = 1901-1922), participants in the BASE-II sample (year of birth: mean = 1939; SD = 3.22 years; range = 1925-1949) reported lower levels of external control beliefs (d = -1.01) and loneliness (d = -0.63). Cohorts did not differ in subjective age, availability of very close others, and internal control beliefs. CONCLUSION: Taken together, our findings suggest that some aspects of psychosocial function of older adults have improved across the two recent decades. We discuss the possible role of sociocultural factors that might have led to the observed set of cohort differences.

Grey-matter structure in cortical and limbic regions correlates with general cognitive ability in old age.

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.

Change in body weight of older adults before and during the COVID-19 pandemic: longitudinal results from the Berlin Aging Study II.

OBJECTIVES: Change 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. DESIGN: Prospective cohort study with three follow-up examinations over the course of 10 years. SETTING AND PARTICIPANTS: In 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). MEASUREMENTS: Body 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. RESULTS: On 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). CONCLUSION: During 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.

Self-reported and accelerometer-based assessment of physical activity in older adults: results from the Berlin Aging Study II.

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.

The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance.

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.