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Aging-related dopamine decline has been suggested as a key factor behind individual differences in cognitive decline at older ages. Thus far, the hypothesized age-dopamine-cognition triad has been extrapolated from cross-sectional studies, which cannot uncover change associations. Using data from the longitudinal Cognition, Brain, and Aging (COBRA) study, we examined whether dopamine D2-receptor availability changes are correlated with cognitive changes across individuals in old age. At the first wave, 181 healthy adults aged 64 to 68 years underwent positron emission tomography with 11C-raclopride, magnetic resonance imaging, multiple cognitive tests assessing episodic memory, working memory, and perceptual speed, and mapping of health-related factors. The returnees (n = 129 after 5 years; n = 93 after 10 years) were representative of the parent sample regarding gender composition, educational attainment, cognitive performance, and dopamine D2-receptor status at baseline. Bayesian structural equation modeling revealed mean decline and individual differences in decline for striatal dopamine D2-receptor availability (approximately-5% per decade) and for all three cognitive abilities. Changes in dopamine D2-receptor and a factor of general cognition were positively correlated (r = 0.31, P(r > 0.00) > 0.95). Taken together, these longitudinal findings support that striatal dopamine decline is associated with cognitive aging, possibly reflecting dopamine influences via striato-Thalamo-cortical loops on general cognitive functions.

Although age differences in the dopamine system have been suggested to contribute to age-related cognitive decline based on cross-sectional data, recent large-scale cross-sectional studies reported only weak evidence for a correlation among aging, dopamine receptor availability, and cognition. Regardless, longitudinal data remain essential to make robust statements about dopamine losses as a basis for cognitive aging. We present correlations between changes in D2/3 dopamine receptor availability and changes in working memory measured over 5 yr in healthy, older adults (n = 128, ages 64 to 68 yr at baseline). Greater decline in D2/3 dopamine receptor availability in working memory-relevant regions (caudate, middle frontal cortex, hippocampus) was related to greater decline in working memory performance in individuals who exhibited working memory reductions across time (n = 43; caudate: rs = 0.494; middle frontal cortex: rs = 0.506; hippocampus; rs = 0.423), but not in individuals who maintained performance (n = 41; caudate: rs = 0.052; middle frontal cortex: rs = 0.198; hippocampus; rs = 0.076). The dopamine–working memory link in decliners was not observed in the orbitofrontal cortex, which does not belong to the core working memory network. Our longitudinal analyses support the notion that aging-related changes in the dopamine system contribute to working memory decline in aging.

Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Methods: Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by ¹¹C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline.

Results: Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men.

Conclusions: These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity.

Normal aging is associated with decline in dopamine function. Factors associated with individual differences in dopamine decline rates remain unclear but are important to map to spare dopamine-related functions, such as cognition. Here we focused on manifestations of cerebral small-vessel disease from magnetic resonance imaging (white-matter lesions, lacunes, and perivascular space dilation) and vascular risk factors (e.g., hypertension, body mass index (BMI), and hyperlipidemia). We assessed striatal dopamine D2-like receptor (DRD2) reductions across five years in healthy, older adults (n = 129, ages: 64–68 years at baseline) using 11C-raclopride/positron emission tomography. Manifestations of confluent lesions and lacunes at baseline had additive effects on DRD2 decline. Individuals with both manifestations showed fastest DRD2 decline rates (∼ −4 %), followed by those with one manifestation (∼ −2 %), whereas individuals spared of confluent lesions and lacunes showed stable DRD2 levels over time (∼ 0 % change). Furthermore, individuals with confluent lesions or lacunes showed more marked decline in perceptual speed performance, as compared to individuals spared of these manifestations (p < 0.05). Higher systolic blood pressure and lower BMI at baseline were associated with faster 5-year DRD2 decline in the putamen (r = -0.17, p < 0.05) and caudate (r = 0.23, p < 0.05), respectively. Together, confluent lesions and lacunes explained up to 8 % of striatal DRD2 change, and up to 10 % when adding hypertension and BMI to the model. These findings suggest that hallmarks of SVD and certain vascular risk factors predispose faster DRD2 decline in aging and may thus serve as factors to consider in future interventions.

Objectives: Fatigue is common in patients with chronic pain. However, there is a knowledge gap concerning performance fatigue, cognitive fatigability, and its neural correlates in this patient group. In this study, we therefore aimed to investigate the presence of cognitive fatigability and its neural correlates in patients with chronic pain using functional magnetic resonance imaging (fMRI).

Methods: In this study 24 women with chronic pain and 22 healthy controls, aged 18–45 years, underwent a 20-minute psychomotor vigilance task (PVT) assessing reaction time during blood-oxygen-level dependent (BOLD) fMRI. Reaction time and BOLD signal changes were analyzed using dual regression.

Results: The patients showed significant cognitive fatigability, i.e., prolonged reaction time, during the PVT, while the controls maintained a stable performance (p = .018). No significant neural time on task effect was found on BOLD fMRI. There were however differences in the brain areas activated between the groups throughout task performance. Patients with chronic pain showed stronger activation primarily in prefrontal cortex, including motor areas, while healthy controls demonstrated stronger activation particularly in the left middle orbital gyrus and right insula.

Conclusion: The study indicates that the phenomenon of cognitive fatigability is present in patients with chronic pain. Also, the presence of chronic pain was associated with increased activation in brain regions related to motor and cognitive control, possibly reflecting compensatory mechanisms. Conversely, healthy controls showed higher activity in regions active in motivation, reward, and decision-making, suggesting more motivation-driven and efficient processing.

Further studies are needed to validate the results.

Many individuals usebackground noise to aid concentration on tasks, yet its effect on workingmemory, especially for those with ADHD, is not well understood. This studyexamined how background white noise influences short-term serial recall inadults with self-reported ADHD (n = 66) and those without (n = 66), controllingfor anxiety and depression. Participants performed a visual-verbal serialshort-term memory task under two conditions: continuous white noise interruptedby quiet intervals (omission deviant) and continuous quiet interrupted by whitenoise (addition deviant). Results showed that addition deviants disruptedperformance more in non-ADHD adults, while omission deviants had a greater disruptiveeffect on adults with self-reported ADHD. These findings suggest thatinterruptions in background sound may differently affect individuals with ADHDsymptoms. Exploratory analyses showed the absence of a primacy effect in adultswith self-reported ADHD. Future research might explore optimal auditoryenvironments tailored to attention differences in those with and without ADHD.

Objectives: Episodic memory is typically declining in older age but some Superagers have high performance levels. A superager level of performance may be preceded by different trajectories. The purpose of this study was to use longitudinal data to assign Superagers to stable or declining trajectories and then consider variation in memory trajectories in analyses of predictors of Superaging.

Methods: In the longitudinal Betula study we identified 139 Superagers (Mean age=79 years) with as good or higher episodic memory as the average of 300 50–60 years old individuals. Episodic-memory trajectories of 125 Superagers were defined from up to 25 years of longitudinal data. The Betula database provided information on possible predictors of Superaging, including education, cognition, polygenic scores, health, lifestyle, and structural brain integrity.

Results: The majority of Superagers were on stable trajectories from initially high to average levels, but some were on declining trajectories from high levels. Similar longitudinal profiles were seen on a word-fluency task. Analyses of predictors of Superaging revealed that education and a polygenic score for cognition were related to initial memory level, and that a polygenic score for dementia was related to rate of change. Most but not all superagers with high-stable memory had favorable education and polygenic predictor scores, suggesting alternative pathways to Superaging. Longitudinal imaging data revealed less atrophy in entorhinal cortex and hippocampus for Superagers.

Conclusion: A superager performance level can reflect well-maintained memory or decline from high initial levels, with distinct factors explaining variability in initial level or stability over time. Medial-temporal lobe brain maintenance characterizes episodic-memory Superagers.

Various studies have reported an association between physical activity and grey matter volumes. Some studies have suggested that this relationship may be moderated by sex, yet the direction is still under debate. Focusing on hippocampus and dorsolateral prefrontal cortex (dlPFC), we tested whether the association between regional grey matter volumes and self-reported physical activity differs between women and men. We examined this interaction in five European cohorts from the Lifebrain consortium (n = 1809; age range: 18–88 years). Effect sizes were first determined by linear models run separately for each cohort, then pooled across datasets in a random-effects meta-analysis. Contrary to our hypotheses, there was no evidence of a relationship between physical activity and hippocampal or dlPFC volumes, nor was there a moderation by sex. Our null findings raise the question of whether self-report questionnaires of physical activity, which commonly feature in big datasets, are sufficiently sensitive to capture a—presumably modest—association between physical activity levels and grey matter outcomes. We conclude that the reliance on self-report questionnaires of physical activity is sub-optimal for brain-behaviour analyses.

BACKGROUND: Various studies have reported an association between physical activity and grey matter volumes. Some studies have suggested that this relationship may be moderated by sex, yet the direction is still under debate.

METHOD: Focusing on hippocampus and dorsolateral prefrontal cortex (dlPFC), we tested whether the association between regional grey matter volumes and self-reported physical activity differs between women and men. We examined this interaction in five European cohorts from the Lifebrain consortium (n = 1,809; age range: 18 - 88 years). Effect sizes were first determined by linear models run separately for each cohort, then pooled across datasets in a random-effects meta-analysis.

RESULT: Contrary to our hypotheses, there was no evidence of a relationship between physical activity and hippocampal or dlPFC volumes, nor was there a moderation by sex.

CONCLUSION: Our null findings raise the question of whether self-report questionnaires of physical activity, which commonly feature in big datasets, are sufficiently sensitive to capture a - presumably modest - association between physical activity levels and grey matter outcomes. We conclude that the reliance on self-report questionnaires of physical activity is sub-optimal for brain-behaviour analyses.

Motivated by the Swedish Betula study, we consider the joint modeling of longitudinal memory assessments and the hazard of dementia. In the Betula data, the time-to-dementia onset or its absence is available for all participants, while some memory measurements are missing. In longitudinal studies of aging, one cannot rule out the possibility of dropout due to health issues resulting in missing not at random longitudinal measurements. We, therefore, propose a pattern-mixture sensitivity analysis for missing not-at-random data in the joint modeling framework. The sensitivity analysis is implemented via multiple imputation as follows: (i) multiply impute missing not at random longitudinal measurements under a set of plausible pattern-mixture imputation models that allow for acceleration of memory decline after dropout, (ii) fit the joint model to each imputed longitudinal memory and time-to-dementia dataset, and (iii) combine the results of step (ii). Our work illustrates that sensitivity analyses via multiple imputations are an accessible, pragmatic method to evaluate the consequences of missing not at-random data on inference and prediction. This flexible approach can accommodate a range of models for the longitudinal and event-time processes. In particular, the pattern-mixture modeling approach provides an accessible way to frame plausible missing not at random assumptions for different missing data patterns. Applying our approach to the Betula study shows that worse memory levels and steeper memory decline were associated with a higher risk of dementia for all considered scenarios.