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Speech comprehension in noisy environments depends on central auditory functions, which are vulnerable in Alzheimer's disease (AD). Binaural processing exploits two ear sounds to optimally process degraded sound information; its characteristics are poorly understood in AD. We studied behavioral and electrophysiological alterations in binaural processing among 121 participants (AD = 27; amnestic mild cognitive impairment [aMCI] = 33; subjective cognitive decline [SCD] = 30; cognitively normal [CN] = 31). We observed impairment of binaural processing in AD and aMCI, and detected a U-shaped curve change in phase synchrony (declining from CN to SCD and to aMCI, but increasing from aMCI to AD). This improvement in phase synchrony accompanying more severe cognitive stages could reflect neural adaptation for binaural processing. Moreover, increased phase synchrony is associated with worse memory during the stages when neural adaptation apparently occurs. These findings support a hypothesis that neural adaptation for binaural processing deficit may exacerbate cognitive impairment, which could help identify biomarkers and therapeutic targets in AD.

Background: Assessing health-related quality of life in dementia poses challenges due to patients’ cognitive impairment. It is unknown if the newly introduced EQ-5D five-level version (EQ-5D-5L) is superior to the 3-level version (EQ-5D-3L) in this cognitively impaired population group. Objective: To assess the psychometric properties of the EQ-5D-5L in comparison to the EQ-5D-3L in patients living with dementia (PwD). Methods: The EQ-5D-3L and EQ-5D-5L were assessed via interviews with n = 78 PwD at baseline and three and six months after, resulting in 131 assessments. The EQ-5D-3L and EQ-5D-5L were evaluated in terms of acceptability, agreement, ceiling effects, redistribution properties and inconsistency, informativity as well as convergent and discriminative validity. Results: Mean index scores were higher for the EQ-5D-5L than the EQ-5D-3L (0.70 versus 0.64). Missing values occurred more frequently in the EQ-5D-5L than the EQ-5D-3L (8%versus 3%). Agreement between both measures was acceptable but poor in PwD with moderate to severe cognitive impairment. The index value’s relative ceiling effect decreased from EQ-5D-3L to EQ-5D-5L by 17%. Inconsistency was moderate to high (13%). Absolute and relative informativity increased in the EQ-5D-5L compared to the 3L. The EQ-5D-5L demonstrated a lower discriminative ability and convergent validity, especially in PwD with moderate to severe cognitive deficits. Conclusion: The EQ-5D-5L was not superior as a self-rating instrument due to a lower acceptability and discriminative ability and a high inconsistency, especially in moderate to severe dementia. The EQ-5D-3L had slightly better psychometric properties and should preferably be used as a self-rating instrument in economic evaluations in dementia.

Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer’s disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline. Further, we aimed to determine whether tau-PET-informed personalized cognitive composites capture patient-specific cognitive trajectories more sensitively than conventional cognitive measures. Methods We included Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants classified as controls (i.e., amyloid-negative, cognitively normal, n = 121) or Alzheimer’s disease-spectrum (i.e., amyloid-positive, cognitively normal to dementia, n = 140), plus 111 AVID-1451-A05 participants for independent validation (controls/Alzheimer’s disease-spectrum=46/65). All participants underwent baseline 18F-flortaucipir tau-PET, amyloid-PET, and longitudinal cognitive testing to assess annual cognitive changes (i.e., episodic memory, language, executive functioning, visuospatial). Cognitive changes were calculated using linear mixed models. Independent meta-analytical task-fMRI activation maps for each included cognitive domain were obtained from the Neurosynth database and applied to tau-PET to determine tau-PET signal in cognitive-domain-specific brain regions. In bootstrapped linear regression, we assessed the strength of the relationship (i.e., partial R2) between cognitive-domain-specific tau-PET vs. global or temporal-lobe tau-PET and cognitive changes. Further, we used tau-PET-based prediction of domain-specific decline to compose personalized cognitive composites that were tailored to capture patient-specific cognitive decline. Results In both amyloid-positive cohorts (ADNI [age = 75.99±7.69] and A05 [age = 74.03±9.03]), cognitive-domain-specific tau-PET outperformed global and temporal-lobe tau-PET for predicting future cognitive decline in episodic memory, language, executive functioning, and visuospatial abilities. Further, a tau-PET-informed personalized cognitive composite across cognitive domains enhanced the sensitivity to assess cognitive decline in amyloid-positive subjects, yielding lower sample sizes required for detecting simulated intervention effects compared to conventional cognitive endpoints (i.e., memory composite, global cognitive composite). However, the latter effect was less strong in A05 compared to the ADNI cohort. Conclusion Combining tau-PET with task-fMRI-derived maps of major cognitive domains facilitates the prediction of domain-specific cognitive decline. This approach may help to increase the sensitivity to detect Alzheimer’s disease-related cognitive decline and to determine personalized cognitive endpoints in clinical trials.

Background: Treatment decisions based on guidelines rather than patients’ preferences determine adherence to and compliance with treatment, which, in turn, could improve health-related outcomes. Objectives: To summarize the stated treatment and care preferences of people with dementia (PwD). Methods: A systematic review was conducted to assess the stated preferences of PwD. The inclusion criterion was the use of quantitative methods to elicit stated preferences, enabling a ranking of preferences. Results: Eleven studies revealed preferences for diagnostics, treatment decisions, patient-related outcomes, care services, end-of-life care, leisure activities, and digital life story work. PwDs prefer accurate, pain-free, and comfortable diagnostic procedures without radioactive markers as well as being accompanied by a caregiver. PwD’s quality of life (QoL), self-efficacy, and depression were equally most important for PwD and caregivers. However, PwD memory was only important for caregivers but not for PwD, and caregiver QoL was moderately important for PwD but least important for caregivers. Additionally, comfort and family involvement were most important for patients’ end-of-life care, whereas caregivers most preferred good communication and pain management. Also, preferences depend on the living situation: Patients living not alone prefer a regular care provider most, whereas those living alone only want to live nearby the caregiver. Preferences for leisure activities did not differ between past and present ratings, indicating that PwD prefer activities that have always been carried out. Conclusion: Only a few studies have applied quantitative methods to elicit the preferences of PwD. More research is needed to capture the stated preferences for the treatment, care, and support of PwD to improve health-related outcomes and the allocation of healthcare resources.

Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

Dealing with memory loss is a major challenge for older people. Coping strategies for memory problems could enable cognitively impaired people to live independently for longer. We conducted a systematic review to summarize evidence on coping strategies for older people and people with cognitive impairment to stabilize everyday life functioning.We systematically searched the databases PubMed, PsychInfo, Scopus and WebofScience using a well-defined search string. Studies were included if they were published between January 1990 and February 2021 and written in English, German, Spanish, French, or Swedish language. Two blind researchers independently checked the studies for inclusion and exclusion criteria and evaluated the quality of the studies using Critical Appraisal Skills Programme-checklists. Evidence was summarized in a narrative synthesis.A total of 16 relevant studies with adequate quality were identified. These studies reported on three categories of strategies: external, internal, and behavioral coping strategies. External strategies included reminder systems and integrated features in the environment and were used by people with and without cognitive impairments. Internal strategies such as visualization, verbalization, active remembering, and systematic thinking were reported less often by people with cognitive impairment than those without cognitive impairment. Behavioral strategies such as reducing expectations and acceptance of support was most frequently reported by people with cognitive impairment.The findings of our systematic review show a great number of coping strategies, which seem to depend on cognitive status. Appropriate training tools incorporating these strategies should be developed.

Background: Social cognition (SC) is a core criterion for neurocognitive disorders. However, findings in patients with amnestic mild cognitive impairment (aMCI) and dementia of the Alzheimer type (DAT) are inconsistent. Objective: We report assessments of emotion recognition (ER), affective and cognitive theory of mind (ToM) in young (YC) and older controls (OC) compared to aMCI and DAT. Methods: 28 aMCI, 30 DAT, 30 YC, and 29 OC received tests of SC and a comprehensive neuropsychological assessment. Analysis of covariance was used to determine group differences. Multiple regression models were applied to identify predictors for each SC task. Results: In controls, OC performed worse in ER and both ToM tasks compared to YC except for one subtest. No significant differences were found between OC and patients concerning ER and affective ToM. In cognitive ToM, differences between OC and patients depended on content and cognitive load with significant impairment in DAT compared to OC. A cognitive composite score predicted SC in OC, but not in patients. Associations of SC with single cognitive domains were found in all groups with language and complex attention as best predictors. Not all variance of SC performance was explained by variance in cognitive domains. Conclusion: Lower performance on SC tasks in OC versus YC was confirmed, although not all tasks were equally affected. With progressive cognitive impairment, cognitive ToM is more impaired than ER or affective ToM. SC seems to be at least partly independent of other cognitive domains, justifying its inclusion in batteries for dementia diagnostic.

OBJECTIVE Subjective cognitive decline (SCD), the earliest symptom in preclinical Alzheimer's disease (AD), is insufficient to identify individuals at risk for AD dementia. Therefore, we aimed to investigate whether function in instrumental activities of daily living (IADL) contributes to identification. METHODS We analysed data of cognitively unimpaired participants of the prospective German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) and its extension, the Study on Needs, Health Service Use, Costs and Health-related Quality of Life in a Large Sample of Oldest-old Primary Care Patients (AgeQualiDe), collected over 10.5 years. Development of AD dementia was quantified as incidence rates (IRs) per 1000 person-years. Cox regression was used to assess the association of SCD and IADL function in regard to incident AD dementia. RESULTS Of 1467 included individuals, 792 (54.0%) reported SCD at baseline. Impaired IADL were present in 50 (3.4%) individuals. IR for AD dementia was highest in individuals with SCD and impaired IADL (49.7; 95% CI, 24.8-99.3). Unadjusted and adjusted Cox analyses revealed an increased AD dementia risk for individuals with SCD and impaired IADL (uHR = 6.1; 95% CI, 2.9-13.0; P

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health-care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.

InstructionIn Parkinson’s disease (PD), activities of daily living (ADL) impairments are crucial for diagnosis of dementia (PDD). Performance-based tests are promising tools to discriminate between different levels of cognitive impairment in PD; however, the value of those tests for diagnosis of PDD is only sparsely investigated. Therefore, we evaluated the Erlangen Test of Activities of Daily Living (E-ADL), a time-efficient performance-based ADL test, in PD.MethodIn this cross-sectional study, 40 PD patients with normal cognition (PD-NC), 45 patients with mild cognitive impairment (PD-MCI) and 21 patients with PDD were assessed with a comprehensive ADL and cognitive test battery.ResultsInterrater reliability (rs =.86) indicated high consistency of the standardized E-ADL scoring system between raters. The E-ADL correlated significantly with other tests of ADL functions (p

Purpose Mild cognitive impairment (MCI) is a widespread phenomenon, especially affecting older individuals. We will analyze in how far MCI affects different facets of quality of life (QOL). Methods We used a sample of 903 participants (110 with MCI) from the fifth follow-up of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe), a prospective longitudinal study, to analyze the effects of MCI on different facets of the WHOQOL-OLD. We controlled for age, gender, marital status, education, living situation, daily living skills, and the ability to walk, see, and hear. Results Univariate analyses showed that individuals with MCI exhibited lower QOL with regard to the facets autonomy; past, present, and future activities; social participation; and intimacy, but less fears related to death and dying. No significant difference was shown with regard to the facet sensory abilities. In multivariate analyses controlling for age, gender, marital status, education, living situation, daily living skills, and the ability to walk, see and hear, MCI-status was significantly associated with QOL in the facet autonomy. Conclusion Effects of MCI go beyond cognition and significantly impact the lives of those affected. Further research and practice will benefit from utilizing specific facets of QOL rather than a total score.

Contains fulltext : 220327.pdf (Publisher’s version ) (Closed access) The present study explores the associations of soluble TREM2, an important regulator of microglial activity linked to Alzheimer's disease (AD), with other known inflammatory proteins in cerebrospinal fluid (CSF). We studied 303 participants, including 89 controls, 135 mild cognitive impairment, and 79 AD dementia patients. Using established CSF biomarkers, subjects were classified according to the National Institute on Aging-Alzheimer's Association research framework, which groups markers into those of amyloid-beta deposition (A), tau pathology (T), and neurodegeneration (N). TNFR1, TNFR2, TGF-beta 1, TGF beta 2, IL-9, TNF-alpha, ICAM1, and VCAM1 showed significant concentration differences between the ATN groups, with higher concentrations in more advanced disease categories. sTREM2 was positively associated with the pro-inflammatory proteins TNF-a, TNFR1, TNFR2, ICAM1, VCAM1, and IP-10 and negatively with IL-21; also, positive associations with the anti-inflammatory proteins TGF beta 1, IL-10, and IL-9 were found. Pathway enrichment analysis highlighted the involvement of sTREM2 in key functional clusters including immunoglobulin and cytokine production and cellular response to lipopolysaccharides, cytokines, and steroid hormones. Our work provides further evidence in support of TREM2 as amarker of neuroinflammatory response in AD. 12 p.

Structural deterioration and volume loss of the hippocampal formation is observed in many diseases associated with memory decline. Paradoxically, glucose metabolism of the hippocampal formation can be increased at the same time. This might be a consequence of compensatory (beneficial) or maladaptive (detrimental) mechanisms. Aim of this study was to differentiate between compensation and maladaptation by analyzing the association between glucose metabolism in the hippocampal formation measured by positron emission tomography with the glucose analogue 18F-fluorodeoxyglucose and cognitive performance as characterized by the extended Consortium to Establish a Registry for Alzheimer's Disease test battery in a sample of 87 patients (81.8 ± 5.4 years) with mild cognitive impairment or mild dementia and varying etiological diagnoses. Glucose metabolism in the hippocampal formation was negatively correlated with the performance in several cognitive subdomains, most pronounced for verbal semantic fluency, independent of overall neuronal dysfunction, presence of clinical Alzheimer's disease, and overall cognitive performance. This finding provides evidence that increased glucose metabolism in the hippocampal formation of cognitively impaired patients indicates detrimental maladaptation rather than a beneficial compensatory reaction. Excess glucose metabolism in the hippocampal formation might be a useful therapeutic target in these patients.

Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driving represents a complex task for which multiple central resources are needed. In mild cognitive impairment and dementia, we need to closely monitor driving ability, as it gets irrecoverably lost in the course of the disease. In normal aging, people are often able to self-regulate driving behavior with respect to their medical conditions. Some studies demonstrated that older drivers perform well compared with younger drivers. Others suggest a decline of driving ability in the process of normal aging and an increasing involvement of older drivers in car crashes. However, these findings have been questioned because of several possible biases. Therefore, unnecessary driving restrictions need to be avoided. The reliable evaluation of driving ability requires a specialist assessment with detailed neurocognitive evaluation, investigation of medical history and medical history by proxy, as well as on-the-the-road tests. Highlighting current knowledge in this field, we would like to increase our readers’ awareness for the complexity of driving-associated challenges in an aging population.

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 There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. OBJECTIVE We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). METHODS We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. RESULTS A significant effect of group on FNART test performance in the total sample was found (p

Objectives: \ud Delayed recall of the first words of a list - the primacy position – is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI).\ud Methods: \ud We investigated serial position performance in 88 subjects with aMCI using a 16-word list (CVLT). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes.\ud Results: \ud After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or delayed recall. Primacy performance during learning was associated with the right inferior and middle temporal gyrus as well as the right inferior parietal cortex and supramerginal gyrus. During delayed recall, primacy performance was related to the bilateral supramarginal gyri.\ud Conclusions: \ud Our findings suggest a reduced primacy effect in aMCI already during learning, contrasting previous findings in normal cognitive aging. This might indicate impaired encoding and consolidation processes at an early stage of episodic memory acquisition. Furthermore, our data indicates that hippocampal volume may not be a relevant determinant of residual primacy performance in the stage of aMCI, which may rather depend on temporal and parietal neocortical networks.

ObjectiveTo determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD).MethodWe analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions. We compared groups in terms of global and domain-specific performance and correlated performance with different CSF markers of AD pathology.ResultsWe observed worse performance (Cohen d = ≈0.25–0.5, adjusted for age, sex differences with analysis of covariance) in global performance, memory, executive functions, and language abilities for the SCD group compared to healthy controls. In addition, worse performance in these domains was moderately (r = ≈0.3) associated with lower CSF β-amyloid42/40 and CSF β-amyloid42/phosphorylated tau181 in the whole sample and specifically in the SCD subgroup.ConclusionsWithin the spectrum of clinically unimpaired (i.e., before mild cognitive impairment) cognitive performance, SCD is associated with minor deficits in memory, executive function, and language abilities. The association of these subtle cognitive deficits with AD CSF biomarkers speaks to their validity and potential use for the early detection of underlying preclinical AD.

Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

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.

The aim of this study was to identify determinants of outpatient health care utilization among the oldest old in Germany longitudinally. Multicenter prospective 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). Individuals in very old age were recruited via GP offices at six study centers in Germany. The course of outpatient health care was observed over 10 months (two waves). Primary care patients aged 85 years and over (at baseline: n=861, with mean age of 89.0 years±2.9 years; 85–100 years). Self-reported numbers of outpatient visits to general practitioners (GP) and specialists in the past three months were used as dependent variables. Widely used scales were used to quantify explanatory variables (e.g., Geriatric Depression Scale, Instrumental Activities of Daily Living Scale, or Global Deterioration Scale). Fixed effects regressions showed that increases in GP visits were associated with increases in cognitive impairment, whereas they were not associated with changes in marital status, functional decline, increasing number of chronic conditions, increasing age, and changes in social network. Increases in specialist visits were not associated with changes in the explanatory variables. Our findings underline the importance of cognitive impairment for GP visits. Creating strategies to postpone cognitive decline might be beneficial for the health care system.

OBJECTIVES This study examines the relationship between late-life depressive symptoms, cognitive and functional impairment in a cohort of very old community-based participants. METHODS A sample of 1,226 primary care patients was assessed at baseline (Mage = 80.6 years). Statistical analyses were conducted using baseline and 12-month follow-up data. RESULTS At baseline, depressed participants showed minor cognitive deficits compared with nondepressed participants, whereas functional deficits were pronounced. Depressive symptoms and global cognition were not associated longitudinally. In contrast, follow-up functional impairment was predicted by baseline level and increase of depressive symptoms between baseline and follow-up. Reversely, follow-up depressive symptoms were predicted by functional decline between baseline and follow-up, whereas baseline functional status was not predictive. DISCUSSION Depressive symptoms and global cognitive function were not associated longitudinally, but level and increase of depressive symptoms over time predicted functional impairment after 1 year. Interventions to reduce depressive symptoms, or to encourage coping strategies might be promising to reduce functional impairment. Elevated follow-up depressive symptoms were only predicted by functional decline, supposedly emphasizing that incident functional impairment might be associated with an acute increase of depressive symptoms. Psychological adjustment processes were not examined, but might be targeted in future.

Background Subjective cognitive decline is related to greater risk of dementia and biological markers of Alzheimer's disease (AD), but researchers are yet to characterize the phenomenological perspective of cognitive decline in those with and without a diagnosis of AD. Objective To collate and synthesize studies measuring the subjective experience of cognitive change or decline in healthy older adults and those with mild cognitive impairment and AD. Methods We reviewed 58 peer-reviewed articles that were found to directly or indirectly refer to the subjective experience of cognitive decline. Results We extracted eight central themes, dealing with cognitive changes experienced by each diagnostic group, and also related to issues of changing self-identity, the causal attribution of cognitive decline, the anxiety and concern related to perceived decline, the negative perceptions attached to a diagnosis of dementia, changing levels of insight, and perception of well-being in aging. Conclusion This review is the first step toward characterizing phenomenological profiles of cognitive change in both non-demented and demented older adults. Developing a clearer understanding of subjective cognitive decline, particularly at the earliest stages of AD, will augment the sensitivity of detection of individuals at greater risk of future dementia.

Objective: To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD). Methods: We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates. Results: Abnormal CSF β-amyloid 1–42 (Aβ42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF Aβ42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF Aβ42 together with either high CSF tau or CSF phosphorylated tau 181 levels. Conclusions: In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.

Background Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. Objective We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Methods Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. Results AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Conclusion Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism.

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.

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.

Non-pharmacological interventions have the potential to reduce cognitive decline and to improve psychosocial aspects in mild cognitive impairment and Alzheimer's dementia, and the absence of side effects makes them a favorable option also for preventive strategies. We provide an overview on recent studies involving cognitive training and reminiscence, stimulating and challenging experiences such as visual art and music, physical activities, and electromagnetic stimulation. We review findings on neuroplasticity in the aging brain and their relevance for cognitive improvement in patients with neurodegenerative diseases. We discuss cognitive reserve and possible mechanisms that drive neuroplasticity and new learning. Finally, we identify promising avenues for future intervention strategies and research, such as combinations of cognitive and pharmaceutical interventions, and individual strategies adapted to the disease stage and tailored to the needs, predispositions and preferences of patients.

Objective Progression from cognitive impairment (CI) to dementia is predicted by several factors, but their relative importance and interaction are unclear. Method We investigated numerous such factors in the AgeCoDe study, a longitudinal study of general practice patients aged 75+. We used recursive partitioning analysis (RPA) to identify hierarchical patterns of baseline covariates that predicted dementia-free survival. Results Among 784 non-demented patients with CI, 157 (20.0%) developed dementia over a follow-up interval of 4.5 years. RPA showed that more severe cognitive compromise, revealed by a Mini-Mental State Examination (MMSE) score

Recent studies have shown that patients with Alzheimer's disease (AD) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions. Few studies so far have used an active control condition and determined effects in different stages of disease. We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a randomized controlled pilot study on subjects with amnestic mild cognitive impairment (aMCI) and mild AD patients. Forty-three subjects with aMCI and mild AD were recruited. Primary outcome measures were change in global cognitive function as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini Mental Status Examination (MMSE). Secondary outcomes were specific cognitive and psychopathological ratings. Thirty-nine patients were randomized to intervention groups (IGs: 12 aMCI, 8 AD) and active control groups (CGs: 12 aMCI, 7 AD). At the end of the study, we found significant improvements in the IG(MCI) compared to the CG(MCI) in the ADAS-cog (p = 0.02) and for the secondary endpoint Montgomery Asberg Depression Rating Scale (MADRS) (p < 0.01) Effects on the MMSE score showed a non-significant trend (p = 0.07). In AD patients, we found no significant effect of intervention on the primary outcome measures. In conclusion, these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects. In contrast, AD patients showed no significant benefit from intervention. The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects.