Factors Associated with Lower Social Activity in German Older Adults at Increased Risk of Dementia: A Cross-Sectional Analysis.

Background: Studies demonstrate associations between low social activity in older adults and cognitive decline. Little has been investigated regarding which factors are associated with low social activity in older adults at increased risk of dementia. Objective: We investigate which sociodemographic, psychological, health-related, and environmental factors are associated with low social activity in older adults at increased risk of dementia. Additionally, we describe the stages of health behavior change, the types of social activities, and the duration of the current level of social activity. Methods: We used baseline data of 1,015 participants from the AgeWell.de trial. We conducted logistic and Poisson regression analyses to investigate factors associated with low social activity. We report descriptive statistics on the stages of change in the sample, the types of social activities most frequently pursued, and the duration of the current level of social activity. Results: Lower income, non-usage of public transport, depressive symptoms, cognitive, mobility, and hearing impairment were negatively associated with social activity. The majority of the sample was in the maintenance stage, followed by the precontemplation stage. The most common social activities were traveling and hobbies with others. Participants have maintained their current level of social activity for several years. Conclusions: We identified a lack of resources (income, transport), depressive symptoms and poorer health (cognitive, mobility and hearing impairment) as barriers to social activity. Interventions promoting social activity in older adults at risk of dementia may specifically target individuals with these risk factors. Low-threshold opportunities for social activity may be particularly beneficial.

A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.

INTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.

Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease.

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

Associations of Depressive Symptoms with Subjective Cognitive Decline in Elderly People-A Cross-Sectional Analysis from the AgeWell.de-Study.

To develop effective dementia prevention strategies, it is necessary to understand risk factors, associated factors and early signs of dementia. Subjective cognitive decline (SCD) is the earliest form of dementia. The aim of this study is to assess depression as a factor that is significantly associated with SCD. The data of 1030 general practitioner patients from the AgeWell.de-study (60-77 years; CAIDE dementia risk score ≥ 9) were analysed. A descriptive analysis was conducted using validated instruments like the Geriatric depression scale (GDS), Lubben social network scale (LSNS-6) and education classes according to CASMIN (Comparative Analysis of Social Mobility in Industrial Nations). A multivariate regression model with the dependent variable SCD was calculated. Of the 1030 participants, 5.9% had depressive symptoms and 31.3% SCD. The group with depressive symptoms showed significantly higher body-mass-index (p = 0.005), lower education class (p = 0.022), lower LSNS-6 score (p < 0.001), higher sports activity (p < 0.001), and more sleeping problems (p = 0.026). In the regression model a higher GDS-score [Odds ratio (OR): 1.219 (p < 0.001)], more sleeping problems [OR: 1.550 (p = 0.017)] and higher education class [middle/high: OR: 1.474/1.875 (p = 0.037/0.004)] were significantly associated with SCD. This study identified depressive symptoms, sleeping problems, and higher education classes as factors associated with SCD, which can represent an early form of dementia.

COVID-19 government measures and their impact on mental health: a cross-sectional study of older primary care patients in Germany.

Background: With the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany. Methods: Data were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support. Results: We analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p < 0.001). The association was no longer significant when adding stress and covariates (b = 0.04; p = 0.43), while stress was linked to increased depressive symptoms (b = 0.22; p < 0.001). A final model confirms the assumption that the feeling of restriction is mediated by stress (total effect: b = 0.26; p < 0.001). Conclusion: We found evidence that feeling restricted due to COVID-19 government measures is associated with higher levels of depressive symptoms in older adults at increased risk for dementia. The association is mediated by perceived stress. Furthermore, social support was significantly associated with less depressive symptoms. Thus, it is of high relevance to consider possible adverse effects of government measures related to COVID-19 on mental health of older people.

Depression and Anxiety in Old Age during the COVID-19 Pandemic: A Comparative Study of Individuals at Cardiovascular Risk and the General Population.

Our study aims to examine the associations of sociodemographic factors, social support, resilience, and perceptions of the COVID-19 pandemic with late-life depression and anxiety symptoms in a cardiovascular risk group and a matched sample from the German general population during the beginning of the pandemic and draw a comparison regarding psychosocial characteristics. Data of n = 1236 participants (aged 64-81 years) were analyzed, with n = 618 participants showing a cardiovascular risk profile, and n = 618 participants from the general population. The cardiovascular risk sample had slightly higher levels of depressive symptoms and felt more threatened by the virus due to pre-existing conditions. In the cardiovascular risk group, social support was associated with less depressive and anxiety symptoms. In the general population, high social support was associated with less depressive symptoms. Experiencing high levels of worries due to COVID-19 was associated with more anxiety in the general population. Resilience was associated with less depressive and anxiety symptoms in both groups. Compared to the general population, the cardiovascular risk group showed slightly higher levels of depressive symptomatology even at the beginning of the pandemic and may be supported by addressing perceived social support and resilience in prevention programs targeting mental health.

Social Network and Participation in Elderly Primary Care Patients in Germany and Associations with Depressive Symptoms-A Cross-Sectional Analysis from the AgeWell.de Study.

This study aims to describe social network and social participation and to assess associations with depressive symptoms in older persons with increased risk for dementia in Germany. We conducted a cross-sectional observational study in primary care patients (aged 60−77) as part of a multicenter cluster-randomized controlled trial (AgeWell.de). We present descriptive and multivariate analyses for social networks (Lubben Social Network Scale and subscales) and social participation (item list of social activities) and analyze associations of these variables with depressive symptoms (Geriatric Depression Scale). Of 1030 included patients, 17.2% were at risk for social isolation (Lubben Social Network Scale < 12). Looking at the subscales, a reduced non-family network was found almost twice as often as a reduced family network. Patients with depressive symptoms had significantly smaller social networks than patients without depression (p < 0.001). They rather engaged in social activities of low involvement level or no weekly social activity at all (p < 0.001). The study shows associations of depressive symptoms with a decreased social network and less social participation in elderly participants. Sufficient non-family contacts and weekly social activities seem to play an important role in mental health and should be encouraged in elderly primary care patients.

Association of mental demands in the workplace with cognitive function in older adults at increased risk for dementia.

OBJECTIVES: Growing evidence suggests a protective effect of high mental demands at work on cognitive function in later life. However, evidence on corresponding associations in older adults at increased risk for dementia is currently lacking. This study investigates the association between mental demands at work and cognitive functioning in the population of the AgeWell.de-trial. METHODS: Cross-sectional investigation of the association between global cognitive functioning (Montreal Cognitive Assessment) and mental demands at work in older individuals at increased risk for dementia (Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)score ≥ 9; n = 941, age: 60-77 years). Occupational information was matched to Occupational Information Network (O*NET)-descriptors. Associations between cognitive function and O*NET-indices executive, verbal and novelty were investigated using generalized linear models. RESULTS: Higher values of index verbal (b = .69, p = .002) were associated with better cognitive function when adjusting for covariates. No association was observed for indices executive (b = .37, p = .062) and novelty (b = .45, p = .119). Higher education, younger age, and employment were linked to better cognitive function, while preexisting medical conditions did not change the associations. Higher levels of depressive symptomatology were associated with worse cognitive function. CONCLUSIONS: Higher levels of verbal demands at work were associated with better cognitive function for older adults with increased dementia risk. This suggests an advantage for older persons in jobs with high mental demands even after retirement and despite prevalent risk factors. Longitudinal studies are warranted to confirm these results and evaluate the potential of workplaces to prevent cognitive decline through increased mental demands.

Health-related quality of life and ego integrity among the oldest old - Evidence from the multicenter AgeCoDe-AgeQualiDe study.

PURPOSE: To investigate the association between health-related quality of life and ego integrity among the oldest old. MATERIALS AND METHODS: Cross-sectional data were taken from follow-up wave 9 of the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe). Our analytical sample comprised n = 495 observations. Mean age was 90.2 years (SD: 2.7 years). Health-related quality of life was quantified using the EQ-5D-3L questionnaire (including the visual analogue scale EQ-VAS). Ego integrity was measured using the Ego Integrity Scale. RESULTS: Regressions showed an association between decreased ego integrity and problems with 'usual activities', 'pain/discomfort' and 'anxiety/depression'. Furthermore, regressions showed a marginally significant association between decreased ego integrity and problems with 'mobility' and a decreased EQ-VAS score. Ego integrity was not significantly associated with problems with 'self-care'. CONCLUSIONS: Findings stress the importance of health-related quality of life for ego integrity among the oldest old. Future studies are required to clarify the underlying mechanisms.

Recruitment and Baseline Characteristics of Participants in the AgeWell.de Study-A Pragmatic Cluster-Randomized Controlled Lifestyle Trial against Cognitive Decline.

Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences.

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology.

Selective neuronal vulnerability of human hippocampal CA1 neurons: lesion evolution, temporal course, and pattern of hippocampal damage in diffusion-weighted MR imaging.

The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n=50), limbic encephalitis (n=30), after status epilepticus (n=17), and transient global amnesia (n=53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.

Stress-related factors in the emergence of transient global amnesia with hippocampal lesions.

The transient global amnesia (TGA) is a rare amnesic syndrome that is characterized by an acute onset episode of an anterograde and retrograde amnesia. Its origin is still debated, but there is evidence for psychological factors involved in TGA. In neuroimaging, selective lesions in the CA1 field of the hippocampus can be detected, a region that is particularly involved in the processing of memory, stress and emotion. The aim of this study was to assess the role of psychological stress in TGA by studying the prevalence of stress related precipitating events and individual stress-related personality profiles as well as coping strategies in patients. The hypothesis of a functional differentiation of the hippocampus in mnemonic and stress-related compartments was also evaluated. From all 113 patients, 18% (n = 24) patients experienced emotional and psychological stress episodes directly before the TGA. In a cohort of 21 acute patients, TGA patients tend to cope with stress less efficiently and less constructively than controls. Patients who experienced a stress related precipitant event exhibited a higher level of anxiety in comparison to non-stress patients and controls. However, there was no difference between the general experience of stress and the number of stress inducing life events. The majority of patients (73%) did show typical magnetic resonance imaging (MRI) lesions in the CA1 region of the hippocampal cornu ammonis. There was no clear association between stressful events, distribution of hippocampal CA1 lesions and behavioral patterns during the TGA. Disadvantageous coping strategies and an elevated anxiety level may increase the susceptibility to psychological stress which may facilitate the pathophysiological cascade in TGA. The findings suggest a role of emotional stress factors in the manifestation of TGA in a subgroup of patients. Stress may be one trigger involved in the emergence of transient lesions in the hippocampal CA1 region, which are thought to be the structural and functional correlate of TGA.

CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness.

Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories.