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Research suggests that inflammation is linked to both late-onset depression (LOD) and cognitive decline, and that LOD might have biological underpinnings differentiating it from recurrent depression. Evidence from inflammatory proteome analyses in large prospective cohorts is scarce. The aim of this study was to assess whether and which inflammation-related biomarkers are associated with LOD, recurrent depression, and cognitive decline due to vascular pathology (vascular dementia).Ongoing population-based cohort study of older adults followed for up to 17 years with regard to clinical diagnosis of various age-related diseases (ESTHER study, n = 9,940).Longitudinal cohort started in 2000-2002 in a community setting in Saarland, a southwestern German state.Subgroup of randomly selected participants of the ESTHER study (n = 1,665).Inflammatory biomarkers were measured with the Olink Target 96 in baseline samples.Out of 78 biomarkers interleukin 10 (IL-10) and C-C chemokine ligand 4 (CCL4) were associated with significantly increased risk of LOD after multiple testing correction. Hazard ratios (95-confidence interval) per 1 standard deviation increase were 1.37 (1.15-1.63) for IL-10 and 1.34 (1.13-1.59) for CCL4. None of the inflammatory markers was associated with recurrent depression. The dose-response analysis showed a similar monotonic risk increase for LOD and vascular dementia with increasing IL-10 levels.These results suggest that inflammatory markers are involved in the etiology of LOD, but not of recurrent depression and that LOD and vascular dementia might share common inflammatory etiology with respect to IL-10.

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.

Within the elderly population, psychogeriatric patients may be particularly susceptible to negative mental health effects of the coronavirus crisis. Detailed information about the psychosocial well-being of psychogeriatric patients during the pandemic is still sparse. Here we examined which aspects of subjective experience of the COVID-19 pandemic especially affect levels of depression, anxiety and quality of life in psychogeriatric patients with and without cognitive impairment. A cross-sectional paper survey was conducted during the first German lockdown among patients with a diagnosed psychiatric disorder (≥ 60 years) or a diagnosed neurodegenerative disease (regardless of their age) from the department for neurodegenerative diseases and geriatric psychiatry at the University of Bonn. The WHO-5-, GAD-7- and WHOQOL-old score were used to determine levels of depression, anxiety and quality of life. The second part obtained information about the subjective experience of the COVID-19 pandemic. Statistical analysis included among others principal component analysis and multiple linear regression analysis. COVID-19-related, immediate distress was a strong predictor of elevated symptoms of depression, anxiety and a reduced quality of life. COVID-19-related concerns regarding health and financial security, however, were not significantly associated with negative mental health outcomes. The overall prevalence of symptoms of depression (50.8% [95% CI 43.8–57.6%]) and anxiety (32.7% [95% CI 26.4–39.2%]) among psychogeriatric patients was high. Our findings indicate that psychogeriatric patients are not significantly affected by COVID-19-related concerns but are primarily suffering from emotional consequences resulting from changed living conditions due to the pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s00406-021-01340-1.

Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.

Background Postoperative delirium is a common complication of cardiac surgery associated with higher morbidity, longer hospital stay, risk of cognitive decline, dementia, and mortality. Geriatric patients, patients undergoing cardiac surgery, and intensive care patients are at a high risk of developing postoperative delirium. Gold standard assessments or biomarkers to predict risk factors for delirium, cognitive decline, and dementia in patients undergoing cardiac surgery are not yet available. Methods The FINDERI trial (FINd DElirium RIsk factors) is a prospective, single-center, observational study. In total, 500 patients aged ≥ 50 years undergoing cardiac surgery at the Department of Cardiovascular and Thoracic Surgery of the University of Göttingen Medical Center will be recruited. Our primary aim is to validate a delirium risk assessment in context of cardiac surgery. Our secondary aims are to identify specific preoperative and perioperative factors associated with delirium, cognitive decline, and accelerated dementia after cardiac surgery, and to identify blood-based biomarkers that predict the incidence of postoperative delirium, cognitive decline, or dementia in patients undergoing cardiac surgery. Discussion This prospective, observational study might help to identify patients at high risk for delirium prior to cardiac surgery, and to identify important biological mechanisms by which cardiac surgery is associated with delirium. The predictive value of a delirium screening questionnaire in cardiac surgery might be revealed. Finally, the identification of specific blood biomarkers might help to predict delirium, cognitive decline, and dementia in patients undergoing cardiac surgery. Trial registration: Ethics approval for this study was obtained from the IRB of the University of Göttingen Medical Center. The investigators registered this study in the German Clinical Trials Register (DRKS; https://www.drks.de) (DRKS00025095) on April 19th, 2021.

Background: The number of patients with dementia is forecast to grow continuously. However, there are indications that the incidence and prevalence is falling in high-income countries. Objective: To examine whether any effects of declining incidence and prevalence rates of dementia and mild cognitive impairment (MCI) were evident in Germany between 2015 and 2019. Methods: The analysis was based on 797 general and 132 specialists (neurological/psychiatric) practices and included 10.1 million patients aged 18 years and older who visited between January 2014 and December 2019 one of the practitioners. The prevalence and incidence of dementia and MCI were demonstrated descriptively. Results: Between 2015 and 2019, the prevalence (incidence) of dementia decreased from 2.18%(0.44%) in 2015 to 2.07%(0.35%) in 2019. A relatively large decrease in the prevalence (incidence) of dementia was observed in patients aged 80 and older, at –1.47%(–0.62%), compared to younger patients, at –0.40%(–0.18%). By contrast, the prevalence and incidence of MCI have remained constant over the years (0.19%to 0.22%and 0.06%, respectively). Overall, the number of patients diagnosed with dementia decreased slightly by 1%while the number of patients diagnosed with MCI increased by 17%. Conclusion: Our results confirmed the reduction in the prevalence and incidence of dementia and revealed a decrease in the number of patients with dementia despite continued demographic changes. Future studies are warranted to determine whether the results are caused by changing risk and lifestyle factors or changes in medical diagnosis and treatment behavior of the practitioners.

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbid neurodegenerative pathology, which is common in elderly individuals and can contribute to the clinical expression of PSCID. Manifestations of cerebral small vessel disease, such as covert brain infarcts, white matter lesions, microbleeds, and cortical microinfarcts, are also common in patients with stroke and likewise contribute to cognitive outcomes. Although studies of PSCID historically varied in the approach to timing and methods of diagnosis, most of them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid cognitive or functional decline, life-course exposure to vascular risk factors, and a history of prior stroke increase risk of PSCID. Stroke characteristics, in particular stroke severity, lesion volume, lesion location, multiplicity and recurrence, also influence PSCID risk. Understanding the complex interaction between an acute stroke event and preexisting brain pathology remains a priority and will be critical for developing strategies for personalized prediction, prevention, targeted interventions, and rehabilitation. Current challenges in the field relate to a lack of harmonization of definition and classification of PSCID, timing of diagnosis, approaches to neurocognitive assessment, and duration of follow-up after stroke. However, evolving knowledge on pathophysiology, neuroimaging, and biomarkers offers potential for clinical applications and may inform clinical trials. Preventing stroke and PSCID remains a cornerstone of any strategy to achieve optimal brain health. We summarize recent developments in the field and discuss future directions closing with a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome.

Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.Design, Setting, and Participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Exposures: Alzheimer disease biomarkers detected on PET or in CSF.Main Outcomes and Measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).Conclusions and Relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

Calcium/Calmodulin-dependent kinase alpha (αCaMKII) has been shown to play an essential role in synaptic plasticity and in learning and memory in animal models. However, there is little evidence for an involvement in specific memories in humans. Here we tested the potential involvement of the αCaMKII coding gene CAMK2A in verbal logical memory in two Caucasian populations from Germany, in a sample of 209 elderly people with cognitive impairments and a sample of 142 healthy adults. The association of single nucleotide polymorphisms (SNPs) located within the genomic region of CAMK2A with verbal logical memory learning and retrieval from the Wechsler Memory Scale was measured and hippocampal volume was assessed by structural MRI. In the elderly people, we found the minor allele of CAMK2A intronic SNP rs919741 to predict a higher hippocampal volume and better logical memory retrieval. This association was not found in healthy adults. The present study may provide evidence for an association of a genetic variant of the CAMK2A gene specifically with retrieval of logical memory in elderly humans. This effect is possibly mediated by a higher hippocampal volume. published

Background: Clinical trials have demonstrated a significant effectiveness of Ginkgo biloba therapy versus placebo in patients with dementia. Objective: The present study aims to analyze the impact of Ginkgo biloba drug prescriptions on dementia incidence in patients with mild cognitive impairment (MCI) in a real-world setting. Methods: This retrospective study was based on the IQVIA Disease Analyzer database and included patients aged 65 or older with a first diagnosis of MCI from January 2000 to December 2019. Each patient was followed for up to 20 years after MCI diagnosis until February 2021. Date of the first diagnosis of dementia or loss to follow-up, whichever occurred first, was noted. To estimate the association between Ginkgo biloba prescriptions during the follow-up and dementia incidence, a multivariable Cox regression analysis was performed, adjusted for age, sex, health insurance, documented co-diagnoses, and prescription of cholinesterase inhibitors. Results: Overall, 24,483 MCI patients (mean age: 77.0 years, 56.3% women) were included. It was found that > 2 prescriptions of Ginkgo biloba were significantly associated with a reduced dementia incidence (HR: 0.71 (95% CI: 0.55–0.91), p = 0.007), as compared with no Ginkgo biloba prescription. The effect of receiving > 3 Ginkgo biloba prescriptions was even stronger, with an HR of 0.64 (95% CI: 0.48–0.86), p = 0.003), while for > 4 prescriptions the HR was 0.58 (95% CI: 0.41–0.82) (p = 0.002). Conclusion: All-cause dementia incidence decreased with higher numbers of Ginkgo biloba prescriptions in MCI patients.

Background: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy. Objective: We evaluated whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study. Methods: 2,092 participants (mean±SD, age 61±9) completed Food Frequency Questionnaires, averaged across a maximum of 3-time points (examination cycles 5, 6, and 7), cognitive testing at examination cycle 7 (present study baseline: 1998–2001) and after a mean±SD of 6.6±1.1 years from baseline (n = 1,584). A subset of participants also completed brain magnetic resonance imaging (MRI) at examination cycle 7 (n = 1,904). In addition, participants with dementia, stroke, and other relevant neurological diseases such as significant head trauma, subdural hematoma, or multiple sclerosis were excluded from the analyses. Results: Higher MIND diet scores were associated with better global cognitive function (β±SE,+0.03SD±0.01; p = 0.004), verbal memory, visual memory, processing speed, verbal comprehension/reasoning, and with larger total brain volume (TBV) following adjustments for clinical, lifestyle and demographic covariates, but not with other brain MRI measures (i.e., hippocampal volume, lateral ventricular volume, white matter hyperintensity volume, and SBIs) or cognitive decline. Conclusion: Higher MIND diet scores associated with better cognitive performance and larger TBV at baseline, but not with cognitive decline. Clinical trials are needed to ascertain whether adopting the MIND diet affects trajectories of cognitive decline.

IntroductionCurrent analysis approaches of accelerometry data use sum score measures which do not provide insight in activity patterns over 24 hours, and thus do not adequately depict circadian activity patterns. Here, we used a functional approach to analyze accelerometer data that models activity pattern and circadian rhythm. As a test case, we demonstrated its application in patients with mild cognitive impairment (MCI) and age-matched healthy older volunteers (HOV). Moreover, we assessed the impact of chronotype on distribution of activity data.MethodsData of two studies were pooled for this analysis. Following baseline cognitive assessment participants were provided with accelerometers for seven consecutive days. A function on scalar regression (FoSR) approach was used to analyze 24 hours accelerometer data. In a second step, analyses were controlled for chronotype using the German version of the morningness-eveningness questionnaire (d-MEQ).ResultsInformation on 47 HOV (mean age 66 SD 6 years) and 13 patients with MCI (mean age 69, SD 8 years) were available for this analysis. MCI patients displayed slightly higher activity in the morning hours as compared to HOV (maximum relative activity at 7:35 am: 75.6%, 95% CI 2.6 to 200.4%, p = 0.031). After controlling for d-MEQ, disturbed activity patterns were found in MCI of intermediate or evening chronotype, compared to HOV, i.e., MCI presented with higher activities in the morning hours (peak at 8:40 am: 357.6%, 95% CI 92.9 to 985.1, p < 0.001) and early afternoon hours (peak at 1:40 pm: 401.8%, 95% CI 63.9 to 1436.4, p < 0.001).DiscussionUsing a novel approach of FoSR, we found timeframes with higher activity levels in MCI patients compared to HOV which were not evident if sum scores of amount of activity were used. In addition, we found that previously described activity patterns as a function of chronotype swere altered in MCI patients, possibly indicating that changes in circadian rhythmicity in neurodegenerative disease are detectable using easy-to-administer accelerometry.Clinical TrialsEffects of Brain Stimulation During Nocturnal Sleep on Memory Consolidation in Patients With Mild Cognitive Impairments, https://clinicaltrials.gov/ct2/show/NCT01782391?term=NCT01782391&rank=1,ClinicalTrial.gov identifier: NCT01782391Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment,https://clinicaltrials.gov/ct2/show/NCT01782365?term=NCT01782365&rank=1,ClinicalTrial.gov identifier: NCT01782365

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia.Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models.Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E epsilon 4 (1.8 [1.3-2.5]) increased the risk of dementia.Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts. (C) 2018 The Authors. Published by Elsevier Inc.

ObjectiveTo investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality.MethodsFollowing the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models.ResultsWe included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias.ConclusionsPresence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.

BackgroundCognitive impairment is an important determinant in health care. In the acute hospital setting cognition has a strong impact on treatment and care. Cognitive impairment can negatively affect diagnostics and treatment success. However, little is known about the individual situation and specific risks of people with cognitive impairments during hospital stays. The aim of the present research is to describe and analyze the treatment needs of people with cognitive impairments in acute hospital care.MethodsThe analyses use baseline data of the ongoing multisite, longitudinal, randomized controlled intervention trial intersec-CM (Supporting elderly people with cognitive impairment during and after hospital stays with Intersectoral Care Management), which recruited 402 participants at baseline. We assessed sociodemographic aspects, cognitive status, functional status, frailty, comorbidities, level of impairment, formal diagnosis of dementia, geriatric diagnoses, delirium, depression, pharmacological treatment, utilization of health care services and health care related needs.ResultsThe sample under examination had been on average mildly cognitively impaired (MMSE M = 22.3) and had a mild to moderate functional impairment (Barthel Index M = 50.4; HABAM M = 19.1). The Edmonton Frail Scale showed a mean of 7.4 and half of the patients (52.3%) had been assigned a care level. About 46.9% had a geriatric diagnosis, 3.0% had a diagnosis of dementia. According to DSM-V 19.2% of the patients had at least one main symptom of depression. The mean number of regularly taken drugs per patient was 8.2. Utilization of health care services prior to the hospital stay was rather low. On average, the sample showed 4.38 care related needs in general, of which 0.60 needs were unaddressed at the time of assessment.ConclusionsDescriptive analyses highlight an in-depth insight into impairments and different care needs of people with cognitive impairments. The results emphasize the need for gender-specific analyses as well as an increased attention to the heterogeneity of needs of people with cognitive impairments related to specific wards, settings and regions where they are admitted. Our results indicate also that people with cognitive impairments represent a high proportion of older patients in acute hospital care.Trial registrationThe intersec-CM trial is registered atClinicalTrials.gov(NCT03359408).

Purpose To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. Methods Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer’s disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. Results In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The ‘alcoholic beverages’ PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. Conclusion In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD.

OBJECTIVES Social deprivation, i.e. the relative deprivation in socioeconomic domains, is known to exacerbate disease risk. Less is known about its role in cognitive functioning and decline in older adults. This study aimed to investigate the association between social deprivation and cognitive status as well as rate of decline. METHODS We analysed data from the nationally representative Health and Retirement study (HRS) of individuals aged 50 and older. The analysis sample contained 11,101 respondents (mean age at baseline: 69.4, SD: 8.6%, 55% female) with at least two cognitive assessments (mean follow up: 11.2, SD: 5.4). To quantify social deprivation we constructed a social deprivation index (SDI) with structural equation modelling. Multiple growth curve modelling was used to model cognitive status and decline as predicted by SDI. RESULTS After adjusting for covariates, greater social deprivation was associated with poorer cognitive status (β = -0.910, p

International audience; Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Cognitive symptoms of Parkinson's disease (PD) have been long underestimated, but are some of the most disabling non-motor features of the disease. In order to establish signs that allow for earlier detection of cognitive decline in PD, the concept of `subjective cognitive decline´ (SCD) has gained a growing interest. SCD refers to patients who report a decline in subjective cognitive capacities, while their results on neuropsychological tests are within the normal performance range, indicating adequate cognitive functions. The aim of this review was to evaluate the concept of SCD in PD and give an overview of the current research. A systematic literature search in PubMed was performed to identify articles published before December 2020. We included 18 studies with a total of n = 2,654 patients. While there is currently no consensus on research or clinical criteria for SCD in PD, this review presents the accumulated evidence for SCD in PD patients and supports the importance of early identification of cognitive deficits, due to the relatively high prevalence for SCD in PD and the added risk of future cognitive impairment it entails. The publications included in this review indicate that SCD may be part of the PD spectrum but further research is needed. Expanding research on SCD in PD will allow for earlier detection of cognitive impairment and may be considered for a preventive intervention.

Introduction Subjective cognitive decline (SCD) is a risk condition for dementia, including dementia of Alzheimer type (DAT). Methods We report sensitivity, specificity, positive and negative predictive values (PPV, NPV) for conversion to all-cause dementia, and DAT in different SCD types (decline in memory, assocated worries, longitudinal consitency, of the AgeCoDe study (n = 2.402, 12 years follow-up). Results 82.7% of those converting to any dementia and 84.4% of those converting with DAT at follow-up, reported memory decline and fulfilled criteria of SCD at least at one time point before. SCD with worries at two consecutive time points showed a specificity of 92.2% for any dementia and also for DAT as well as a PPV of 44.3% for any dementia and of 36.9% for DAT at follow-up at the expense of low sensitivity. Discussion Different SCD subtypes were either sensitive or specific for future all-cause dementia and DAT in cognitively unimpaired individuals. Modest PPV of the most specific SCD subtypes were achieved in this low prevalence population.

Background Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer’s disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries. Methods We analyzed data of n = 687 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, including the diagnostic groups SCD (n = 242), mild cognitive impairment (MCI, n = 115), AD (n = 77), CO (n = 209), and first-degree relatives of AD patients (REL, n = 44). The Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale (GDS-15), and Geriatric Anxiety Inventory (GAI-SF) were used to assess NPS. We examined differences of NPS frequency between diagnostic groups. Logistic regression analyses were carried out to further investigate the relationship between NPS and cerebrospinal fluid (CSF) AD biomarkers, focusing on a subsample of cognitively unimpaired participants (SCD, REL, and CO), who were further differentiated based on reported worries. Results The numbers of reported NPS, depression scores, and anxiety scores were significantly higher in subjects with SCD compared to CO. The quantity of reported NPS in subjects with SCD was lower compared to the MCI and AD group. In cognitively unimpaired subjects with worries, low Aß42 was associated with higher rates of reporting two or more NPS (OR 0.998, 95% CI 0.996–1.000, p Conclusion These findings give insight into the prevalence of NPS in different diagnostic groups, including SCD and healthy controls. NPS based on informant report seem to be associated with underlying AD pathology in cognitively unimpaired participants who worry about cognitive decline. Trial registration German Clinical Trials Register DRKS00007966. Registered 4 May 2015.

Background and Purpose— Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke. Methods— We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status–modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination Results— We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1–5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07–2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status–modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted β, −1.33 [95% CI, −2.65 to −0.02]), without difference in the rate of change over time. Conclusions— In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status–modified during 3-year follow-up. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.

Atrial fibrillation (AF) and dementia are both frequent diseases with substantial socioeconomic impact. While AF has been associated with cognitive dysfunction and dementia, we currently lack an exact understanding of the complex association between AF and cognitive decline. Based on an extended literature search we summarize key publications focusing on AF-related cognitive decline and dementia. Moreover, ongoing trials and potential therapeutic implications are discussed. While further prospective studies using a standardized definition of AF and cognitive decline are urgently needed, growing evidence supports the hypothesis that AF is an independent risk factor for cognitive decline and dementia in general and for Alzheimer's disease in particular. In addition to AF-related ischaemic stroke, white matter damage and systemic inflammation are candidate pathomechanisms and therefore a potential target for prevention of cognitive decline. Whether individualized best-medical therapy of AF holds the promise of preventing cognitive decline should be tested in randomized trials.

Background Several MRI studies have demonstrated hippocampal atrophy in Parkinson's disease (PD), a structure considered a key element in spatial learning. Despite this, no study has been undertaken to investigate spatial navigation in PD using a virtual version of the Morris water maze, which is the gold standard for testing hippocampal function in rodents. Methods We studied 17 cognitively unimpaired PD patients, 12 PD patients with mild cognitive impairment (MCI) and 15 controls in a virtual water maze procedure. Results Measured by the main outcome parameters latency to locate the target and heading error (average difference between direction of movement toward anticipated target and real direction toward the target), controls performed significantly better on the virtual water maze task than cognitively unimpaired PD patients or PD patients with MCI, while there was no significant difference between latter two groups. Conclusions The virtual water maze test differentiates PD patients from controls, but does not distinguish between cognitively normal and cognitively impaired PD patients, indicating a possible dopamine dependent component in spatial learning. Spatial performance deficits might thus constitute very early signs of dopamine depletion independent of the presence of MCI in Parkinson's disease.

BACKGROUND AND PURPOSE Orthostatic hypotension is frequent with aging with a prevalence of 20%-30% in people aged 65 or older and is considered to increase the risk for coronary events, strokes and dementia. Our objective was to characterize the association of orthostatic hypotension and cognitive function longitudinally over 6 years in a large cohort of the elderly aged over 50 years. METHODS In all, 495 participants were assessed longitudinally with the Schellong test and comprehensive cognitive testing using the extended CERAD neuropsychological test battery at baseline and after 6 years. In a subgroup of 92 participants, cerebral magnetic resonance imaging was evaluated for white matter changes using a modified version of the Fazekas score. RESULTS The prevalence of orthostatic hypotension increases with aging reaching up to 30% in participants aged >70 years. Participants with orthostatic hypotension presented with a higher vascular burden index (1.03 vs. 0.69, P ≤ 0.001), tended to have a higher prevalence of cerebral white matter hyperintensities (91.7% vs. 68.8%, P = 0.091) and showed a faster deterioration in executive and memory function (Trail Making Test B 95 vs. 87 s, P ≤ 0.001; word list learning sum -0.53 vs. 0.38, P = 0.002) compared to participants without orthostatic hypotension. CONCLUSION Orthostatic hypotension seems to be associated with cognitive decline longitudinally.

Introduction Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). Methods We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. Results The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p

Background: The CHARIOT PRO Main study is a prospective, non-interventional study evaluating cognitive trajectories in participants at the preclinical stage of Alzheimer’s disease (AD) classified by risk levels for developing mild cognitive impairment due to AD (MCI-AD). Objectives: The study aimed to characterize factors and markers influencing cognitive and functional progression among individuals at-risk for developing MCI-AD, and examine data for more precise predictors of cognitive change, particularly in relation to APOE ε4 subgroup. Design: This single-site study was conducted at the Imperial College London (ICL) in the United Kingdom. Participants 60 to 85 years of age were classified as high, medium (amnestic or non-amnestic) or low risk for developing MCI-AD based on RBANS z-scores. A series of clinical outcome assessments (COAs) on factors influencing baseline cognitive changes were collected in each of the instrument categories of cognition, lifestyle exposure, mood, and sleep. Data collection was planned to occur every 6 months for 48 months, however the median follow-up time was 18.1 months due to early termination of study by the sponsor. Results: 987 participants were screened, among them 690 participants were actively followed-up post baseline, of whom 165 (23.9%) were APOE ε4 carriers; with at least one copy of the allele. The mean age was 68.73 years, 94.6% were white, 57.4% were female, and 34.8% had a Family History of Dementia with a somewhat larger percentage in the APOE ε4 carrier group (42.4%) compared to the non-carrier group (32.4%). Over half of the participants were married and 53% had a Bachelor’s or higher degree. Most frequently, safety events typical for this population consisted of upper respiratory tract infection (10.4%), falls (5.2%), hypertension (3.5%) and back pain (3.0%). Conclusion (clinical relevance): AD-related measures collected during the CHARIOT PRO Main study will allow identification and evaluation of AD risk factors and markers associated with cognitive performance from the pre-clinical stage. Evaluating the psycho-biological characteristics of these pre-symptomatic individuals in relation to their natural neurocognitive trajectories will enhance current understanding on determinants of the initial signs of cognitive changes linked to AD.

Background In the absence of treatment options, the WHO emphasizes the identification of effective prevention strategies as a key element to counteract the dementia epidemic. Regarding the complex nature of dementia, trials simultaneously targeting multiple risk factors should be particularly effective for prevention. So far, however, only few such multi-component trials have been launched, but yielding promising results. In Germany, comparable initiatives are lacking, and translation of these complex interventions into routine care was not yet done. Therefore, AgeWell.de will be conducted as the first multi-component prevention trial in Germany which is closely linked to the primary care setting. Methods AgeWell.de will be designed as a multi-centric, cluster-randomized controlled multi-component prevention trial. Participants will be older community-dwelling general practitioner (GP) patients (60–77 years; n = 1,152) with increased dementia risk according to CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) Dementia Risk Score. Recruitment will take place at 5 study sites across Germany. GP practices will be randomized to either intervention A (advanced) or B (basic). GPs will be blinded to their respective group assignment, as will be the statistician conducting the randomization. The multi-component intervention (A) includes nutritional counseling, physical activity, cognitive training, optimization of medication, management of vascular risk factors, social activity, and, if necessary, further specific interventions targeting grief and depression. Intervention B includes general health advice on the intervention components and GP treatment as usual. We hypothesize that over the 2-year follow-up period the intervention group A will benefit significantly from the intervention program in terms of preserved cognitive function/delayed cognitive decline (primary outcome), and other relevant (secondary) outcomes (e.g. quality of life, social activities, depressive symptomatology, cost-effectiveness). Discussion AgeWell.de will be the first multi-component trial targeting risk of cognitive decline in older adults in Germany. Compared to previous trials, AgeWell.de covers an even broader set of interventions suggested to be beneficial for the intended outcomes. The findings will add substantial knowledge on modifiable lifestyle factors to prevent or delay cognitive decline. Trial registration German Clinical Trials Register (reference number: DRKS00013555).

ObjectivesTo examine how visual impairment affects physical and cognitive function in old age. DesignA longitudinal population-based prospective cohort study. SettingGeneral practitioner offices at six study centers in Germany. They were observed every 1.5 years over four waves. ParticipantsIndividuals aged 77-101 at follow-up Wave 2 (N = 2,394). MeasurementsPhysical and cognitive function were assessed using an adapted scale that had been previously developed, and visual impairment was rated on a Likert scale (none, mild, severe or profound). ResultsAdjusting for sociodemographic factors and comorbidity, linear fixed-effects regression showed that the onset of severe visual impairment was associated with a decline in physical function score in the total sample ( = -0.15, P = .01) and in women ( = -.15, P = .03). Moreover, the onset of severe visual impairment was associated with decline in cognitive function score in the total sample ( = -0.38, P < .001) and in women ( = -0.38, P < .001) and men ( = -0.37, P = .001). ConclusionVisual impairment affects physical and cognitive function in old age. Interventional strategies to postpone visual impairment may contribute to maintaining physical and cognitive function.

Background Efficient help and care for people with dementia (PWD) is dependent on knowledge about PWD in primary care. Objective This analysis comprehensively describes community-dwelling PWD in primary care with respect to various dementia care specific variables. Methods The analyses are based on baseline data of the ongoing general practitioner-based, randomized, controlled intervention trial DelpHi-MV (Dementia: life- and person-centered help). 6,838 patients were screened for dementia in 136 GP practices; 17.1% were screened positive, 54.4% of those agreed to participate and data could be assessed in n = 516 subjects. We assessed age, sex, living situation, cognitive status, functional status, level of impairment, comorbidities, formal diagnosis of dementia, depression, neuropsychiatric symptoms, quality of life, utilization of medical support, and pharmacological therapy. Results Concerning clinical-, dementia-, and health-related variables, the sample under examination was on average mildly cognitively and functionally impaired (MMSE, m = 22.2; BADL, m = 3.7). A level of care was assigned in 38.0%. Depression was identified in 15.4% and other frequent comorbidities were high blood pressure (83.3%), coronary heart diseases (37.1%), cerebrovascular diseases (22.3%), among others. In 48.6%, neuropsychiatric symptoms were present in a clinically relevant severity. Pharmacological treatment with antidementia medication was received by 25.8% and antidepressant medication by 14.0%. Utilization of services was generally low. Conclusion The comprehensive description of people screened positive for dementia in primary care reveals a complex and unique population of patients. They are considerably underdiagnosed and in their majority mildly to moderately affected. More in-depth analyses are needed to study relations, associations and interactions between different variables.

Background; The prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life. Methods: Participants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI). Results: Results show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings. Conclusions: Sufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

Background Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer’s disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. Methods The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer’s dementia patients, first-degree relatives of patients with Alzheimer’s dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets. Results In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer’s Disease Assessment Scale—cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aβ42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected. Conclusions The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aβ42 concentration. Trial registration German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.

Background:Older people have a higher risk of drug-related problems (DRPs). However, little is known about the prevalence of DRPs in community-dwelling people who screened positive for dementia. Our study aimed to determine (1) the prevalence and types of DRPs and (2) the socio-demographic and clinical variables associated with DRPs in people screened positive for dementia in primary care.Methods:The Dementia: life- and person-centered help in Mecklenburg-Western Pomerania (DelpHi-MV) study is a general practitioner (GP)-based cluster-randomized controlled intervention study to implement and evaluate an innovative concept of collaborative dementia care management in the primary care setting in Germany. Medication reviews of 446 study participants were conducted by pharmacists based on a comprehensive baseline assessment that included a computer-based home medication assessment. ClinicalTrials.gov Identifier: NCT01401582.Results:A total of 1,077 DRPs were documented. In 414 study participants (93%), at least one DRP was detected by a pharmacist. The most frequent DRPs were administration and compliance problems (60%), drug interactions (17%), and problems with inappropriate drug choice (15%). The number of DRPs was significantly associated with the total number of drugs taken and with a formal diagnosis of a mental or behavioral disorder.Conclusions:Degree of cognitive impairment (MMSE defined) and formal diagnosis of dementia were not risk factors for an increased number of DRPs. However, the total number of drug taken and the presence of a diagnosis of mental and behavioral disorders were associated with an increased total number of DRPs.

Background\ud \ud Premature-born individuals have an increased risk for long-term neurocognitive impairments. In animal models, the development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that in premature-born individuals cBF integrity is impaired and mediates adult cognitive impairments associated with prematurity.\ud \ud Methods\ud \ud We used MRI-based volumetric assessments of a cytoarchitectonically defined cBF region-of-interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight (VP/VLBW) and 106 term born controls from the same birth cohort. MRI-derived cBF volumes were studied in relation to neonatal clinical complications after delivery as well as intelligence measures (IQ) in adulthood.\ud \ud Results\ud \ud In VP/VLBW adults, cBF volumes were significantly reduced compared to term-born adults (-4.5%, F(1, 202) = 11.82, p = 0.001). Lower cBF volume in VP/VLBW adults was specifically associated with both neonatal complications (rpart(92) = -0.35, p < 0.001) and adult IQ (rpart(88) = 0.33, p = 0.001) even after controlling for global gray matter and white matter volume. In an additional path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits.\ud \ud Conclusions\ud \ud Results provide first time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery.

Background:Subjective cognitive decline (SCD), the potentially earliest notable manifestation of preclinical Alzheimer's disease and other dementias, was consistently associated with lower quality of life in cross-sectional studies. The aim of this study was to investigate whether such an association persists longitudinally – particularly with health-related quality of life (HRQoL) in older individuals without cognitive impairment.Methods:Data were derived from follow-up 2–6 of the prospective Germany Study on Ageing, Cognition and Dementia in Primary Care (AgeCoDe) covering a total six-year observation period. We used linear mixed effects models to estimate the effect of SCD on HRQoL measured by the EQ-5D visual analogue scale (EQ VAS).Results:Of 1,387 cognitively unimpaired individuals aged 82.2 years (SD = 3.2) on average, 702 (50.6%) reported SCD and 230 (16.6%) with SCD-related concerns. Effect estimates of the linear mixed effects models revealed lower HRQoL in individuals with SCD (unadjusted: –3.7 points on the EQ VAS, 95%CI = –5.3 to –2.1; SE = 0.8; p < 0.001; adjusted: –2.9 points, 95%CI = –3.9 to –1.9; SE = 0.5; p < 0.001) than in individuals without SCD. The effect was most pronounced in SCD with related concerns (unadjusted: –5.4, 95%CI = –7.6 to –3.2; SE = 1.1; p < 0.001; adjusted: –4.3, 95%CI = –5.8 to –2.9, SE = 0.7; p < 0.001).Conclusion:SCD constitutes a serious issue to older cognitively unimpaired individuals that is depicted in persisting lower levels of HRQoL beyond depressive symptoms and functional impairment. Therefore, SCD should be taken seriously in clinical practice.

Background Recent studies demonstrated benefits of cognitive intervention in mild cognitive impairment (MCI), but few studies have determined long-term effects on cognition, conversion rate to Alzheimer's disease, and the role of early intervention. Method A 6-month multicomponent cognitive group intervention was applied in participants with single- or multiple-domain amnestic MCI (defined according to Petersen's criteria). One group (n = 12) received the intervention at the beginning of the study period and was compared with an active control group (n = 12) who received it after an 8-month time lag. Follow-up assessments were conducted at 15 and 28 months (study period was August 2007-December 2009). The primary outcome was change in cognitive function as determined by changes in scores on the Mini-Mental State Examination and the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and the secondary outcomes were change in specific cognitive and noncognitive functions and conversion to Alzheimer's disease (according to DSM-IV/NINCDS-ADRDA criteria and NAI-AA criteria for probable Alzheimer's dementia with increased level of certainty). Results Eighteen participants completed the study after 28 months. Long-term data revealed a stable intervention effect on the primary outcome ADAS-cog in the early-intervention group (P = .024). The participants in the later-intervention (control) group appeared to benefit to a lesser extent from the cognitive intervention compared to those who received it earlier. Only participants in the later-intervention group (6 of 12) converted to Alzheimer's disease during the 28-month study period. Conclusions Benefits of our 6-month cognitive intervention on global cognitive status appear to be preserved over extended follow-up periods. Early cognitive intervention may delay conversion to Alzheimer's disease. Findings in a small sample encourage the use of the intervention in larger-scale studies. Trial registration ClinicalTrials.gov identifier: NCT00544856.

Background It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's disease (AD) dementia. Objective We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. Methods We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. Results Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. Conclusion These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Objective Inconsistent results exist regarding the cognitive profile in patients with Parkinson9s disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Methods Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. Results 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson9s Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. Conclusions This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Background Late-life depression is frequently accompanied by cognitive impairments. Objective Whether these impairments indicate a prodromal state of dementia, or are a symptomatic expression of depression per se is not well-studied. Methods In a cohort of very old initially non-demented primary care patients (n = 2,709, mean age = 81.1 y), cognitive performance was compared between groups of participants with or without elevated depressive symptoms and with or without subsequent dementia using ANCOVA (adjusted for age, sex, and education). Logistic regression analyses were computed to predict subsequent dementia over up to six years of follow-up. The same analytical approach was performed for lifetime major depression. Results Participants with elevated depressive symptoms without subsequent dementia showed only small to medium cognitive deficits. In contrast, participants with depressive symptoms with subsequent dementia showed medium to very large cognitive deficits. In adjusted logistic regression models, learning and memory deficits predicted the risk for subsequent dementia in participants with depressive symptoms. Participants with a lifetime history of major depression without subsequent dementia showed no cognitive deficits. However, in adjusted logistic regression models, learning and orientation deficits predicted the risk for subsequent dementia also in participants with lifetime major depression. Conclusion Marked cognitive impairments in old age depression should not be dismissed as "depressive pseudodementia", but require clinical attention as a possible sign of incipient dementia. Non-depressed elderly with a lifetime history of major depression, who remained free of dementia during follow-up, had largely normal cognitive performance.

Midlife motivational abilities, that is, skills to initiate and persevere in the implementation of goals, have been related to mental and physical health, but their association with risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD) has not yet been directly investigated. This relation was examined with data from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). A total of 3,327 nondemented participants (50.3% of a randomly selected sample) aged 75-89 years were recruited in primary care and followed up twice (after 1.5 and 3 years). Motivation-related occupational abilities were estimated on the basis of the main occupation (assessed at follow-up II) using the Occupational Information Network (O* NET) database, which provides detailed information on worker characteristics and abilities. Cox proportional hazards models were used to evaluate the relative risk of developing MCI and AD in relation to motivation-related occupational abilities, adjusting for various covariates. Over the 3 years of follow-up, 15.2% participants developed MCI and 3.0% developed AD. In a fully adjusted model, motivation-related occupational abilities were found to be associated with a reduced risk of MCI (HR: 0.77; 95% CI: 0.64-0.92). Motivation-related occupational abilities were associated with reduced risk of AD in ApoE ε4 carriers (HR: 0.48; CI: 0.25-0.91), but not in noncarriers (HR: 0.99; CI: 0.65-1.53). These results suggest that midlife motivational abilities are associated with reduced risk of MCI in general and with reduced risk of AD in ApoE ε4 carriers. Revealing the mechanisms underlying this association may inform novel prevention strategies for decelerating cognitive decline in old age.

OBJECTIVE:Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. METHODS:Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. RESULTS:Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. CONCLUSION:Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

PURPOSE The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edi- tion (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determi- nants of the future course of MCI in the AgeCoDe study (German Study on Age- ing, Cognition, and Dementia in Primary Care Patients). METHODS We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospec- tively split into 4 groups representing remittent, fluctuating, stable, and progres - sive courses of MCI. We performed ordinal logistic regression analysis and clas- sification and regression tree (CART) analysis. RESULTS Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spec- trum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis. CONCLUSIONS In primary care, about one-quarter of patients with MCI have pro- gression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.

The prediction of Alzheimer's dementia is relevant for the development and design of prevention trials but also for individual counselling of patients. There are two key characteristics which determine the level of prediction that can be achieved. Firstly, the prevalence of Alzheimer's dementia in the respective setting is important. In low prevalence settings, such as primary care populations, it is probably impossible to achieve positive predictive values above 50%. In high prevalence settings, such as memory clinics, the positive predictive value of Alzheimer's dementia can be much higher. The second major characteristic is the level of cognitive impairment of an individual. The predictive power for Alzheimer's dementia increases from the cognitively healthy status to the status of progressive mild cognitive impairment. Prediction can further be increased by the use of cerebral spinal fluid and brain imaging biomarkers of Alzheimer's disease. The combination of different biomarkers may increase prediction even further. The present article reviews studies and outlines the principles of prediction of Alzheimer's dementia.

We sought to provide an overview on the assessment of mild cognitive impairment and dementia in epidemiological studies from Germany.We conducted a literature search in the databases Pubmed and PsycInfo.Literature search identified 31 relevant studies using a broad spectrum of methods and neuropsychological instruments.Further efforts are necessary to establish a generally accepted core set of instruments enabling a harmonized assessment of mild cognitive impairment and dementia in epidemiological studies. Such a core set should comprise neuropsychological tests but also standardized questionnaires on subjective cognitive impairment and impairment in activities of daily living. If possible, third-party information (proxy interviews) should be included.

Objective To compare the risk of developing Alzheimer's disease (AD) dementia in late mild cognitive impairment (LMCI), early MCI (EMCI), and subjective memory impairment (SMI) with normal test performance. Methods The baseline sample (n = 2892) of the prospective cohort study in nondemented individuals (German Study on Aging, Cognition and Dementia in Primary Care Patients) was divided into LMCI, EMCI, SMI, and control subjects by delayed recall performance. These groups were subdivided by the presence of self-reported concerns associated with experienced memory impairment. AD dementia risk was assessed over 6 years. Results Across all groups, risk of AD dementia was greatest in LMCI. In those with self-reported concerns regarding their memory impairment, SMI and EMCI were associated with a similarly increased risk of AD dementia. In those subgroups without concerns, SMI was not associated with increased risk of AD dementia, but EMCI remained an at-risk condition. Conclusions SMI and EMCI with self-reported concerns were associated with the same risk of AD dementia, suggesting that pre-LMCI risk conditions should be extended to SMI with concerns.