Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation.

Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi-kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution; (B) incorporating demographics & clinical covariates; (C) the impact of the size of the training data set; (D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of-sample predictions. The highest performance for Aß42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status.

Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD): Study Design and Protocol.

BACKGROUND: Speech impairments are an early feature of Alzheimer's disease (AD) and consequently, analysing speech performance is a promising new digital biomarker for AD screening. Future clinical AD trials on disease modifying drugs will require a shift to very early identification of individuals at risk of dementia. Hence, digital markers of language and speech may offer a method for screening of at-risk populations that are at the earliest stages of AD, eventually in combination with advanced machine learning. To this end, we developed a screening battery consisting of speech-based neurocognitive tests. The automated test performs a remote primary screening using a simple telephone. OBJECTIVES: PROSPECT-AD aims to validate speech biomarkers for identification of individuals with early signs of AD and monitor their longitudinal course through access to well-phenotyped cohorts. DESIGN: PROSPECT-AD leverages ongoing cohorts such as EPAD (UK), DESCRIBE and DELCODE (Germany), and BioFINDER Primary Care (Sweden) and Beta-AARC (Spain) by adding a collection of speech data over the telephone to existing longitudinal follow-ups. Participants at risk of dementia are recruited from existing parent cohorts across Europe to form an AD 'probability-spectrum', i.e., individuals with a low risk to high risk of developing AD dementia. The characterization of cognition, biomarker and risk factor (genetic and environmental) status of each research participants over time combined with audio recordings of speech samples will provide a well-phenotyped population for comparing novel speech markers with current gold standard biomarkers and cognitive scores. PARTICIPANTS: N= 1000 participants aged 50 or older will be included in total, with a clinical dementia rating scale (CDR) score of 0 or 0.5. The study protocol is planned to run according to sites between 12 and 18 months. MEASUREMENTS: The speech protocol includes the following neurocognitive tests which will be administered remotely: Word List [Memory Function], Verbal Fluency [Executive Functions] and spontaneous free speech [Psychological and/ or behavioral symptoms]. Speech features on the linguistic and paralinguistic level will be extracted from the recordings and compared to data from CSF and blood biomarkers, neuroimaging, neuropsychological evaluations, genetic profiles, and family history. Primary candidate marker from speech will be a combination of most significant features in comparison to biomarkers as reference measure. Machine learning and computational techniques will be employed to identify the most significant speech biomarkers that could represent an early indicator of AD pathology. Furthermore, based on the analysis of speech performances, models will be trained to predict cognitive decline and disease progression across the AD continuum. CONCLUSION: The outcome of PROSPECT-AD may support AD drug development research as well as primary or tertiary prevention of dementia by providing a validated tool using a remote approach for identifying individuals at risk of dementia and monitoring individuals over time, either in a screening context or in clinical trials.

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.

[18F]-florbetaben PET/CT Imaging in the Alzheimer's Disease Mouse Model APPswe/PS1dE9.

BACKGROUND: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aß), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aß plaques. METHODS: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aß plaque load in cortex, hippocampus and cerebellum were analyzed. RESULTS: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. CONCLUSION: The findings suggest that histopathological characteristics of Aß plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

[Unmet needs of family dementia caregivers of persons with dementia : Primary medical care]. / Offene Versorgungsbedarfe pflegender Angehöriger von Menschen mit Demenz : Primärärztliche Versorgung.

BACKGROUND: Results of current research studies revealed that providing informal care for people with dementia (PwD) is associated with caregivers' burden and a variety of health impairments. In order to provide optimal support for family caregivers of PwD, general practitioners and specialists should be able to identify caregivers' unmet needs in primary care. OBJECTIVES: The present article provides an overview of unmet needs of family caregivers that are relevant for general practitioners as well as specialists in neurology, psychiatry, psychotherapy and psychosomatics. MATERIAL AND METHODS: The present overview is based on current reviews on unmet needs of caregivers of PwD and on results of the general practitioner-based, cluster-randomized controlled intervention trial DelpHi-MV (Life- and person-centred help in Mecklenburg-Western Pomerania, Germany; Identifier: NCT01401582). RESULTS: The article provides an overview of unmet needs of family caregivers for PwD, especially in the domains of social integration, psychological and physical health, legal and financial issues, as well as available and valid measurements. DISCUSSION: The article illustrates the importance and the possibilities for general practitioners and specialists to identify caregivers' unmet needs. The question to what extent unmet needs' assessments for family caregivers of PwD could be implemented and financed in routine care is still under debate.

Supporting family dementia caregivers: testing the efficacy of dementia care management on multifaceted caregivers' burden.

OBJECTIVES: Current research suggests that dementia care management (DCM) can decrease burden and associated health impairments of caregivers. The objective of this secondary analysis is to investigate the impact of DCM on multifaceted caregivers' burden dimensions by differentiating between objective and subjective burden. METHODS: A sample of n = 317 dyads of caregivers and community-dwelling people with dementia (PwD) participated in a general practitioner-based, cluster-randomized intervention trial (Identifier:NCT01401582) with two arms and comprehensive data assessment at baseline and 12-month follow-up. Data provided by the caregiver included an inventory with 88 items in 20 different dimensions. RESULTS: Caregivers in the intervention 'DCM' group showed decreased caregiver burden, especially in caregivers' objective burden due to caring (i.e. emotional support), caregivers' subjective burden due to behavior change (i.e. cognition, aggression and resistance, depression, late symptoms) and caregivers' subjective burden due to perceived conflicts between needs and responsibilities to care (i.e. financial losses) compared to caregivers in the control 'care as usual' group, which showed significant increased caregiver burden after 12 months. CONCLUSION: Our findings support evidence for the effectiveness of DCM to lower family dementia caregivers' burden in multifaceted dimensions.

Drug-related problems in community-dwelling primary care patients screened positive for dementia.

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.

[Cognitive rehabilitation in early stage Alzheimer's disease]. / Kognitive Rehabilitation bei Alzheimer-Krankheit im Frühstadium.

BACKGROUND: Dementia impairs the coping with routine daily tasks and social relationships due to an increasing degeneration of cognitive abilities. An appropriate treatment must adequately consider the effects of declined cognitive abilities on patients and their environment. Therefore, in recent times, integrative procedures for cognitive rehabilitation (CR) have become increasingly important for the therapy of patients with mild cognitive impairment (MCI) and mild dementia (MD). CR approaches provide compensatory possibilities for clearly defined routine challenges and the individual needs of those affected. MATERIAL AND METHODS: This overview article in the form of a selective review elaborates factors for the effectiveness of CR on the basis of the currently available literature: 1) individuality - consideration of personal needs and targets, 2) compensation - mediation of skills and strategies to compensate for cognitive impairments, 3) interaction - inclusion of relatives and environmental conditions and 4) integration - integration of various therapeutic disciplines and methods. RESULTS AND DISCUSSION: On the basis of this assessment with regards to the content, a critical analysis of the methods of short and long-term therapeutic effects on MCD and MD was carried out. Although the resulting factors were of high long-term relevance for the improvement of depression and quality of life, effects on cognition were more pronounced for MCI than for MD, which emphasizes the importance of beginning therapy as early as possible. The results show that future studies on effectiveness must employ endpoints relevant for routine daily life, and that the possibility of an implementation of therapeutic concepts in a healthcare system should be considered as an essential criterion.

[A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene]. / Ein Geschwisterpaar mit einer seltenen Tau-Gen-Mutation (MAPT R5H).

We report on a female patient presenting with primary progressive aphasia (PPA) and her brother presenting with psychosis. Both siblings had an R5H-mutation in exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age of 72 years with a 4-year-history of language impairment. After a progressive course the patient died at the age of 76 years. The R5H-MAPT-gene mutation detected in the siblings has been described only once in 2002 by Hayashi et al. [1]. In this previous case from Japan, a 75-year-old patient initially displayed amnesia and disorientation. He became bedridden, with progressive mutism and rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms in R5H-mutations and the late age of onset. For future trials, the detection of biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying subjects at risk.

Cognitive Rehabilitation in Alzheimer's Disease - A Conceptual and Methodological Review.

Within the last 20 years, several standardized cognitive trainings have been developed aiming at the delay of cognitive decline in older people who are at risk of Alzheimer's Disease (AD) or in mild stages of dementia. The transfer of cognitive training effects into activities of daily living was very limited in most previous studies. Therefore, multimodal Cognitive Rehabilitation approaches have been designed that aim to improve the activities of daily living. These approaches also attempt to integrate the patient's psychopathological and behavioral status as well as social relationships into the treatment plan. Contrary to other approaches, CR mainly focuses on compensation rather than restoration of impaired functionality. In this review, we define CR conceptually, and derive specific criteria to evaluate current CR approaches for individuals with mild cognitive impairment (MCI) and AD dementia. In addition, we perform a critical, methodical analysis of available CR studies, reviewing their short- and long-term treatment effects. Findings suggest that CR approaches improve memory performance and competence of activity of daily living (ADL) in mildly cognitively impaired subjects (MCI), when compensatory, integrative, as well as interactive elements and domain specificity are taken into account. Interactive and individual aspects also appear to be relevant to sustain long-term effects. In AD dementia, similar results emerged, although with smaller effect sizes. The efficacy of individualized CR approaches was comparable with theory-based, manual-guided concepts as long as promoting interaction was part of the treatment. So far, only few randomized controlled studies of sufficient sample size are available. Future systematic efficacy studies need to consider precisely defined outcome variables. This is necessary before one can draw conclusions of how CR can be used for secondary prevention of AD dementia as well as AD treatment.

[Hearing impairment and dementia]. / Hörstörung und Demenz.

The World Health Organization (WHO) burden of disease study identified dementia and hearing problems as leading causes of loss of quality of life in the industrial world. The prevalence of dementia and hearing problems increases in aging societies. Comorbidity of these two diseases causes increasing demands on healthcare systems. The similarity and possible interaction of symptoms renders diagnosis and therapy of dementia and hearing loss a challenge for neurologists, psychiatrists, ear, nose and throat (ENT) and hearing specialists. Knowledge of both diseases enables an early intervention and helps preserve participation in society and thereby reducing the risk of developing dementia. This paper focuses on the characteristics of the diagnosis and therapy of hearing problems and dementia.

The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aß) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aß1-42 (Aß1-42), also expressed as Aß1-42 : Aß1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for "prodromal AD" and "mild cognitive impairment due to AD" include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication.

Association of basal forebrain volumes and cognition in normal aging.

The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.

EFNS task force: the use of neuroimaging in the diagnosis of dementia.

BACKGROUND AND PURPOSE: The European Federation of the Neurological Societies (EFNS) guidelines on the use of neuroimaging in the diagnosis and management of dementia are designed to revise and expand previous EFNS recommendations for the diagnosis and management of patients with Alzheimer's disease (AD) and to provide an overview of the evidence for the use of neuroimaging techniques in non-AD dementias, as well as general recommendations that apply to all types of dementia in clinical practice. METHODS: The task force working group reviewed evidence from original research articles, meta-analyses and systematic reviews, published before April 2012. The evidence was classified, and consensus recommendations were given and graded according to the EFNS guidance regulations. RESULTS: Structural imaging, which should be performed at least once in the diagnostic work-up of patients with cognitive impairment, serves to exclude other potentially treatable diseases, to recognize vascular lesions and to identify specific findings to help distinguish different forms of neurodegenerative types of dementia. Although typical cases of dementia may not benefit from routine functional imaging, these tools are recommended in those cases where diagnosis remains in doubt after clinical and structural imaging work-up and in particular clinical settings. Amyloid imaging is likely to find clinical utility in several fields, including the stratification of patients with mild cognitive impairment into those with and without underlying AD and the evaluation of atypical AD presentations. CONCLUSIONS: A number of recommendations and good practice points are made to improve the diagnosis of AD and other dementias.

A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI.

OBJECTIVES: Mild cognitive impairment (MCI) is etiologically heterogeneous, and a substantial proportion of MCI subjects will develop different dementia disorders. One subtype of this syndrome, amnestic MCI, occurs preferentially but not exclusively in prodromal AD and is characterized by defined deficits of episodic memory. DESIGN, SETTING AND PARTICIPANTS: For a 2-year, double-blinded, placebo-controlled study MCI patients, presenting with an amnestic syndrome but not necessarily based on presumed prodromal AD were randomized. INTERVENTION: Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or (b) 16 mg galantamine alone or (c) placebo. MEASUREMENTS: The primary objective was to explore the differential impact of these interventions on the progression to dementia and on cognitive changes as measured by the ADAScog. RESULTS: After recruitment of 232 subjects, the trial was halted before reaching the planned sample size, because safety concerns arose in other studies with galantamine in MCI. This resulted in a variable treatment duration of 2-52 weeks. The statistical analysis plan was amended for studying cognitive effects of discontinuing the study medication, which was done separately for galantamine and memantine, and under double-blind conditions. There was one death, no unexpected severe adverse events, and no differences of severe adverse events between the treatment arms. The cognitive changes on the ADAScog were not different among the groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a significant improvement of ADAScog score over placebo before the discontinuation of medication was observed, while amnestic MCI presumably due to other etiologies showed no cognitive changes with broad variation. Cognitive improvement was numerically larger in the combination treatment group than under galantamine alone. Patients who received placebo declined as expected. Discontinuation of galantamine, either as part of the combination regimen or as mono treatment, resulted in a transient decline of the ADAScog score in amnestic MCI of presumed AD etiology, while discontinuation of Memantine did not change the cognitive status. CONCLUSION: In an interrupted trial with amnestic MCI subjects the combination of galantamine plus memantine were generally well tolerated. In the subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a short-term combination treatment of galantamine plus memantine was observed, and cognitive decline occurred after discontinuation of galantamine.

[Quality features of German memory clinics: a cross-sectional study]. / Qualitätsmerkmale deutscher Memory-Kliniken : Eine Querschnittsuntersuchung.

BACKGROUND: Although memory clinics have become an established institution for diagnosing and treating dementia in Germany over the years, little is known about their quality features. Considering the increasing societal relevance of dementia, memory clinics will most likely gain in importance in the future. MATERIAL AND METHODS: Addresses of German memory clinics were obtained by an online search. All institutions were surveyed via questionnaire with items regarding structural characteristics (designation, affiliation, services offered, funding) and quality features (waiting times, disease severity at diagnosis). RESULTS: The results of the inquiry of all institutions (n=153, response: 48%) show memory clinics as specialised institutions that have a low degree of standardisation, but basically have a high structural quality for diagnostic and therapeutic care. CONCLUSION: The development of homogeneous structure and process standards could help to establish memory clinics in regular care and to establish sustainable funding. In order to achieve this, an even more intensive collaboration and consensus building of all German memory clinics would be needed as well as a coordinated representation of interests.

[Structural and functional neuronal connectivity in Alzheimer's disease: a combined DTI and fMRI study]. / Strukturelle und funktionelle neuronale Konnektivität bei der Alzheimer-Krankheit : Eine kombinierte DTI- und fMRT-Studie.

BACKGROUND: Cognitive performance depends on intact cortical connectivity. Important for memory processing in the human brain is the connection between posterior cingulate cortex and hippocampus, directly as well as indirectly via the parahippocampal gyrus. These brain areas are involved early in Alzheimer's disease (AD). At the same time, they belong to the default mode network (DMN), a functional network showing high functional connectivity under resting state conditions. In AD, this connectivity in specifically compromised, offering the possibility to investigate the structural basis of functional brain connectivity. METHODS: We studied 18 patients with mild to moderate AD, 16 patients with mild cognitive impairment (MCI) and 20 healthy control subjects using diffusion tensor imaging (DTI) and resting state fMRI at 3.0 Tesla. We determined the effect of structural integrity in the posterior cingulate as assessed by DTI on the functional connectivity between posterior cingulate, hippocampus and parahippocampus during resting state in these three groups. RESULTS: Structural integrity was reduced in posterior cingulate fibre tracts in patients with AD in the left hemisphere; however, this effect was partly accounted for by age differences. All three groups showed high functional connectivity between posterior cingulate cortex and hippocampus, via both the direct and the indirect pathways. Determination of effective connectivity yielded a negative fractional anisotropy (FA)-moderated correlation on the direct pathway in AD and MCI for both hemispheres, and in healthy controls for the right hemisphere. The indirect pathway showed a negative FA-moderated correlation in AD for the right hemisphere and in MCI for both hemispheres. Healthy controls showed a positive correlation on the indirect pathway for the left hemisphere. CONCLUSION: Our data suggest that under healthy conditions, effective connectivity in the DMN between posterior cingulate cortex and hippocampus is mainly maintained by the indirect pathway via the parahippocampal gyrus. Patients with AD and patients with MCI show changes in this connectivity with a partial allocation to the direct pathway, most likely reflecting early parahippocampal lesions. The combination of DTI and fMRI broadens our understanding of human brain connectivity and its pathological changes with AD.

Longitudinal changes of fractional anisotropy in Alzheimer's disease patients treated with galantamine: a 12-month randomized, placebo-controlled, double-blinded study.

Diffusion tensor imaging (DTI) demonstrates decline of fractional anisotropy (FA) as a marker of fiber tract integrity in Alzheimer's disease (AD). We aimed to assess the longitudinal course of white matter microstructural changes in AD and healthy elderly control (HC) subjects and to evaluate the effects of treatment with the cholinesterase inhibitor galantamine on white matter microstructure in AD patients. We enrolled 28 AD patients and 11 healthy elderly control subjects (HC). AD patients were randomly assigned to 6-month double-blind galantamine treatment or placebo, with a 6-month open-label extension phase. DTI was performed at baseline, as well as at 6 and 12-month follow-up in AD patients. The HC subjects underwent DTI at baseline and 12-month follow-up without treatment. We measured FA in regions of interest covering the posterior cingulate and corpus callosum. At 6-month follow-up, the AD group showed significant FA decline in the left posterior cingulate. FA decline was significantly preserved in the posterior body of the corpus callosum in AD group with treatment compared to placebo. At 12-month follow-up, the AD patients showed no differences in FA decline between initial treatment and placebo groups after the 6-month open-label extension phase. A significant FA decline occurred in the left posterior cingulate across the AD and HC groups without between-group differences. DTI demonstrated FA decline in intracortically projecting fiber tracts in aging and AD over 1 year. Galantamine had limited impact on regional FA decline, which was not preserved after additional 6-month open-label treatment.

Functional and structural MR imaging in neuropsychiatric disorders, part 2: application in schizophrenia and autism.

SUMMARY: During the past decade, the application of advanced MR imaging techniques in neuropsychiatric disorders has seen a rapid increase. Disease-specific alterations in brain function can be assessed by fMRI. Structural GM and WM properties are increasingly investigated by DTI and voxel-based approaches like VBM. These methods provide neurobiologic correlates for brain architecture and function, evaluation tools for therapeutic approaches, and potential early markers for diagnosis. Having provided insight into principles of functional and structural imaging and delineated common findings in mild cognitive impairment and Alzheimer disease in Part 1 of this review, we will now focus on autism and schizophrenia as common psychiatric disorders covering different stages of the life span. This review concludes by summarizing current applications, limitations, and future prospects in the field of MR imaging-based neuroimaging.

Functional and structural MR imaging in neuropsychiatric disorders, Part 1: imaging techniques and their application in mild cognitive impairment and Alzheimer disease.

During the past decade, the application of advanced MR imaging techniques in neuropsychiatric disorders has seen a rapid increase. Disease-specific alterations in brain function can be assessed by fMRI. Structural GM and WM properties are increasingly investigated by DTI and voxel-based approaches like VBM. These methods provide neurobiologic correlates for brain architecture and function, evaluation tools for therapeutic approaches, and potential early markers for diagnosis. The aim of this review was to provide insight into the principles of functional and structural imaging and to delineate major findings in MCI, AD (Part 1), autism, and schizophrenia (Part 2), which are common psychiatric disorders covering different stages of the life span. Part 2 will conclude by summarizing current applications, limitations, and future prospects in the field of MR imaging-based neuroimaging.