Background: Perivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD. Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean_age = 70.78 ± 5.78) of the ongoing observational multicentre “DZNE Longitudinal Cognitive Impairment and Dementia Study” (DELCODE) cohort. We analysed data from subjects who were cognitively unimpaired (n = 401), had amnestic mild cognitive impairment (n = 71), or had AD (n = 31). We used linear mixed-effects modelling to test for changes of PVS volumes in relation to cross-sectional and longitudinal age, as well as sex, years of education, hypertension, white matter hyperintensities, AD diagnosis, and cerebrospinal-fluid-derived amyloid (A) and tau (T) status (available for 46.71%; A-T-/A + T-/A + T + n = 143/48/39). Results: PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p < 0.001; BG: B = 0.05 [0.03, 0.07], p < 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant’s age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p < 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρ_spearman = -0.17, p_FDR = 0.001) and was more pronounced in individuals who presented with combined amyloid and tau positivity versus negativity (A + T + > A-T-, p_FDR = 0.004) or who were amyloid positive but tau negative (A + T + > A + T-, p_FDR = 0.07). CSO-PVS volumes increased at a faster rate with amyloid positivity as compared to amyloid negativity (A + T-/A + T + > A-T-, p_FDR = 0.021). Conclusion: Our longitudinal evidence supports the relevance of PVS enlargement in presumably healthy ageing as well as in AD pathology. We further discuss the region-specific involvement of white matter hyperintensities and neurotoxic waste accumulation in PVS enlargement and the possibility of additional factors contributing to PVS progression. A comprehensive understanding of PVS dynamics could facilitate the understanding of pathological cascades and might inform targeted treatment strategies. Trial registration: German Clinical Trials Register DRKS00007966. Registered 04.05.2015 – retrospectively registered, https://drks.de/search/en/trial/DRKS00007966.

Restrictive means to reduce the spread of the COVID-19 pandemic have not only imposed broad challenges on mental health but might also affect cognitive health. Here we asked how restriction-related changes influence cognitive performance and how age, perceived loneliness, depressiveness and affectedness by restrictions contribute to these effects. 51 Germans completed three assessments of an online based study during the first lockdown in Germany (April 2020), a month later, and during the beginning of the second lockdown (November 2020). Participants completed nine online cognitive tasks of the MyBrainTraining and online questionnaires about their perceived strain and impact on lifestyle factors by the situation (affectedness), perceived loneliness, depressiveness as well as subjective cognitive performance. The results suggested a possible negative impact of depressiveness and affectedness on objective cognitive performance within the course of the lockdown. The younger the participants, the more pronounced these effects were. Loneliness and depressiveness moreover contributed to a worse evaluation of subjective cognition. In addition, especially younger individuals reported increased distress. As important educational and social input has partly been scarce during this pandemic and mental health problems have increased, future research should also assess cognitive long-term consequences.

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer’s disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aβ42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05–3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57–2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00–1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26–0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid β beyond age.

Decision-making is an important everyday function that deteriorates during normal aging. Here, we asked whether value-based decision-making can be improved in the elderly by cognitive training. We compared the effects of two training regimens on the performance in the Iowa Gambling Task (IGT), a real-life decision-making simulation task. Elderly participants (age 62–75 years) were randomized into three matched groups. The filter training (FT) group performed a selective attention task and the memory training (MT) group performed a memory storage task on five consecutive days. The control group (CG) did not perform another task besides the IGT. Only the FT group showed an improvement in IGT performance over the five days—the overall gain rose and the prominent deck B phenomenon decreased. The latter refers to the selection of cards associated with high gains and rare losses, which are nevertheless a disadvantageous choice as the frequent losses lead to a negative net outcome. As the deck B phenomenon has been associated with impaired cognitive abilities in aging, the positive effect of FT here is of special importance. In sum, attention training seems superior in improving decision-making in the elderly.

Introduction: Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method’s susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks.Methods: We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling.Results: The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity.Discussion: Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.

Introduction We studied brain maintenance, examining the co-evolution of ageing-related atrophy, white matter hyperintensities (WMH), and cognition, alongside domain-specific and domain-general contributions of lifestyle and personality. Methods In 543 cognitively unimpaired DELCODE participants, we modelled four-year interrelations between medial temporal lobe to ventricle ratio (MTLV-ratio), WMH, and PACC5 performance using latent growth curve modelling. We quantified unique contributions of brain changes to cognitive change and derived a domain-general brain maintenance index. Associations with lifestyle and personality were examined post-hoc. Results Steeper MTLV-ratio decline related to baseline WMH and its progression. Brain-domain changes independently contributed to cognitive changes. Neuroticism, depressive symptoms, and low cognitive engagement related to unfavourable domain-specific trajectories and brain maintenance index. Discussion Dynamics of WMH and ageing-related atrophy on cognitive ageing highlight their relevance for brain maintenance. Our results suggest that maintaining cerebrovascular and mental health alongside cognitive engagement could promote brain maintenance, delay cognitive decline and dementia.