Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease.

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.

Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults.

BACKGROUND: Identifying individuals before the onset of overt symptoms is key in the prevention of Alzheimer's disease (AD). OBJECTIVES: Investigate the use of miRNA as early blood-biomarker of cognitive decline in older adults. DESIGN: Cross-sectional. SETTING: Two observational cohorts (CHARIOT-PRO, Alzheimer's Disease Neuroimaging Initiative (ADNI)). PARTICIPANTS: 830 individuals without overt clinical symptoms from CHARIOT-PRO and 812 individuals from ADNI. MEASUREMENTS: qPCR analysis of a prioritised set of 38 miRNAs in the blood of individuals from CHARIOT-PRO, followed by a brain-specific functional enrichment analysis for the significant miRNAs. In ADNI, genetic association analysis for polymorphisms within the significant miRNAs' genes and CSF levels of phosphorylated-tau, total-tau, amyloid-ß42, soluble-TREM2 and BACE1 activity using whole genome sequencing data. Post-hoc analysis using multi-omics datasets. RESULTS: Six miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) were downregulated in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The pathway enrichment analysis indicated involvement of apoptosis and inflammation, relevant in early AD stages. Polymorphisms within genes encoding for hsa-miR-29c-3p and hsa-miR-146a-5p were associated with CSF levels of amyloid-ß42, soluble-TREM2 and BACE1 activity, and 21 variants were eQTL for hippocampal MIR29C expression. CONCLUSIONS: six miRNAs may serve as potential blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within these miRNAs suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study.

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins alpha and beta (sAPP alpha and sAPP beta) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examination >or=20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloid beta peptides, Tau and phospho-Tau. sAPP alpha and sAPP beta were measured with multiplexing method based on electrochemiluminescence. sAPP alpha and sAPP beta CSF concentrations correlated with each other with very high correlation ratio (R=0.96, P<0.001). We observed highly significantly increased sAPP alpha and sAPP beta CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPP alpha and sAPP beta highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPP alpha: cutoff, 117.4 ng ml(-1), sensitivity, 68%, specificity, 85%, P<0.001; sAPP beta: cutoff, 181.8 ng ml(-1), sensitivity, 75%, specificity, 85%, P<0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPP alpha and sAPP beta might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

[Cognitive reserve and its relevance for the prevention and diagnosis of dementia]. / Kognitive Reservekapazität und ihre Bedeutung für Auftreten und Verlauf der Demenz.

Progressive brain damage is undoubtedly the main cause of clinical symptoms of dementia in neurodegenerative disorders such as Alzheimer's disease. However, the association between brain damage and cognitive symptoms is not linear. Certain interindividual differences such as a good school education or a greater brain volume are associated with a higher resilience against brain damage that is usually referred to as cognitive reserve (CR). Individuals with high CR have a diminished risk for dementia and both active and passive concepts for this phenomenon are discussed. In the concept of passive CR, peculiarities of brain structure such as higher synapse or neuron counts are regarded as buffers against brain damage. Symptoms of dementia do not occur until a certain threshold of damage is passed. In addition to the passive concepts, active mechanisms are also discussed that are associated with the ability to maintain a certain level of cognitive performance in the face of progressive neurodegeneration for a longer period. In subjects with healthy cognitive function, these active mechanisms contribute to the adaptation of brain activity when task difficulty level is increased. Confronted with progressive neurodegeneration, these active mechanisms help to compensate for brain damage. Individuals with higher CR show more efficient activation for solving the same task, which helps them to preserve normal levels of cognitive performance for a longer period.

Validation of the German revised Addenbrooke's cognitive examination for detecting mild cognitive impairment, mild dementia in alzheimer's disease and frontotemporal lobar degeneration.

BACKGROUND/AIMS: The diagnostic accuracy of the German version of the revised Addenbrooke's Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer's disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. METHODS: The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. RESULTS: The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. CONCLUSION: The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.

Homocysteine and cognitive function in geriatric depression.

BACKGROUND/OBJECTIVES: Cognitive dysfunction is a common aspect of the spectrum of symptoms of geriatric depression. High homocysteine levels have been linked to cognitive decline in neuropsychiatric disorders. The present study investigated possible associations between cognitive impairment observed in geriatric depression and homocysteine levels. METHODS: The performance of 25 mentally healthy individuals and 40 patients with geriatric depression in terms of language processing, processing speed, concentration and attention was assessed with the Stroop Test and the d2 Test of Attention. Serum homocysteine was determined with an enzyme immunoassay. RESULTS: The performance of depressed patients was significantly worse in language processing (p = 0.001) and processing speed (p < 0.0001). Depressed patients with high levels of homocysteine performed better than patients with homocysteine concentrations

[Personality in old age]. / Persönlichkeit im höheren Lebensalter.

Modern developmental psychology tends to draw a positive, resource-based picture of human aging. We will however focus on more difficult aspects of personality in old age which are of psychiatric relevance: the persistence of cluster A and C personality disorders, antisocial personality in the elderly; the interaction of personality and a detection of mild cognitive impairment (MCI); personality features as risk or protective factors or early signs of Alzheimer's dementia; changes of personality in Parkinson's disease and frontotemporal dementia. We will briefly mention recent neuroimaging studies which appear to suggest a functional neuroanatomy of personality. A quote from Cicero's cato major, de senectute indicates that some of his perceptions regarding classic personality characteristics of the elderly can be recognized in our patients and can be prevented or treated with modern interventions.

Prospective Evaluation of Cognitive Health and Related Factors in Elderly at Risk for Developing Alzheimer's Dementia: A Longitudinal Cohort Study.

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.

Gender differences in brain reserve : an (18)F-FDG PET study in Alzheimer's disease.

BACKGROUND: Neuropathological studies suggest that the association between neurodegenerative brain damage and clinical symptoms may be stronger in women than in men. OBJECTIVE: To test the hypothesis that cerebral metabolic deficits due to neurodegeneration are more pronounced in men than in women at the same level of clinical disease severity. METHODS: 93 patients with mild Alzheimer's disease (AD; 50 men, 43 women) underwent an extensive clinical and neuropsychological examination and (18)F-FDG PET imaging at a university-based outpatient unit for cognitive disorders. An analysis of covariance (with age, total score of the CERAD neuropsychological battery, and years of school education as covariates) was conducted in each study group to identify gender differences in glucose metabolism. RESULTS: Controlling for age, education, and clinical severity, cortical regions were identified,where glucose metabolism was significantly reduced in men as compared with women. These regions were located in areas typically affected by AD pathology (right inferior frontal, superior temporal and insular cortex, and hippocampus). CONCLUSIONS: These data suggest that the same clinical severity of dementia is associated with greater reductions in cerebral metabolism in men than in women suggesting a greater degree of brain reserve in men.

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

BACKGROUND: Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. OBJECTIVE: To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). METHODS: 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. RESULTS: The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. CONCLUSIONS: In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Volume of interest-based [18F]fluorodeoxyglucose PET discriminates MCI converting to Alzheimer's disease from healthy controls. A European Alzheimer's Disease Consortium (EADC) study.

An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs) in each hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine and the AAL VOIs was tested against a validated method (PALZ). At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed.

[Current antidementive therapy]. / Frühzeitige aktuelle antidementive Behandlung zahit sich aus. So helfen Sie Demenzkranken, den Alltag selbst zu meistern

Current antidementive treatment can delay further progress of the symptoms of dementia and should therefore be initiated as early as possible and be of adequate duration. Wherever possible, maximum permissible doses should be given. The efficacy of current antidementive drugs in Alzheimer's disease has been sufficiently documented by relevant studies. The acetylcholinesterase inhibitors, donepezil, galantamine and rivastigmine have been approved for the treatment of mild-to-moderate Alzheimer's dementia, the NMDA inhibitor memantine is approved for moderate-to-severe Alzheimer's disease. Ginkgo biloba or piracetam are alternatives for patients with mild-to-moderate dementia, in whom acetylcholinesterase inhibitors cannot be used.

[Mild cognitive impairment]. / Grossvater wird immer vergesslicher--Schon krankhaft oder noch normal?

From today's point of view, patients with a mild cognitive impairment (MCI) are at risk for developing a dementia. This clinical picture occurs frequently in the population and is easily recognized through simple tests and interviews conducted in the general and neurological medical practice. A goal of the diagnostics is to detect potentially redressable causes, above all depressive disorders, and to introduce a therapy. In many cases, however, MCI is an early stage of Alzheimer's disease or other neurodegenerative processes. When such a cause is suspected, the most important medical measure is to monitor the progression of the disease so that when deterioration occurs, therapy with antidementia drugs can promptly begin. In the future, patients with MCI will play an increasingly important role as the target group for the prevention of dementia.

Soluble amyloid precursor protein ß as blood-based biomarker of Alzheimer's disease.

The aim of this study was to explore concentrations differences of soluble amyloid precursor protein (sAPP) α and ß in blood plasma in patients with probable Alzheimer's disease (AD) and cognitively healthy age-matched control subjects, as well as patients with behavioural variant frontotemporal dementia (bvFTD). Concentrations of sAPPα and ß were measured using enzyme-linked immunosorbent assay technology in 80 patients with probable AD, 37 age-matched control subjects and 14 patients with bvFTD. Concentration differences were explored using parametric tests. Significantly decreased plasma concentrations in the AD group compared with both the control group and the bvFTD group were detected for sAPPß (P = 0.03 for both group comparisons), but not for sAPPα. The study provides a further piece of evidence in support of sAPPß as a promising new biomarker of AD, which may potentially improve the diagnostic accuracy of existing markers and also enable a less invasive diagnostic workup. Further research is required to establish normal ranges and to replicate the results in independent cohorts including larger numbers of participants covering a wider spectrum of cognitive impairment.

Head circumference, apolipoprotein E genotype and cognition in the Bavarian School Sisters Study.

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele is correlated with an earlier onset of Alzheimer's disease symptoms; larger head circumference has been associated with an individual resilience against cognitive impairment. METHODS: We explored if larger head circumference attenuates the effect of the APOE ɛ4 allele on cognition in 380 Catholic sisters covering the spectrum from normal cognitive performance to severe dementia. RESULTS: Linear regression analysis, adjusting for risk factors for cognitive decline, revealed that APOE ɛ4 was correlated with worse cognition and that larger head circumference attenuated the negative effect of the ɛ4 allele on cognitive performance. CONCLUSION: Larger head circumference (i.e. larger brain size) seems to be associated with greater resilience against genetic determinants of cognitive impairment, possibly due to enhanced brain or cognitive reserve.