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Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines (). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (Aβ 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other). Generally, CSF-NDD should be combined with blood-based routine diagnostics and should be part of routine CSF diagnostics, e. g. cell count and cell differentiation (if applicable), intrathecal antibody synthesis and blood-CSF barrier analysis. The CSF-NDD are most valuable for the improved differentiation between reversible dementia syndromes and irreversible neurodegenerative dementia, e. g. cognitive deficits due to late onset depression (pseudodementia due to depression) or AD. Combined with extended psychometric neuropsychological evaluation and neuroimaging methods, such as magnetic resonance imaging (MRI), dopamine transporter scanning (DaTscan) by single photon emission computed tomography (SPECT), 18F-fluorodeoxyglucose positron emission tomography (glucose-PET) and amyloid-PET, CSF-NDD also significantly improve the differential diagnostics within the heterogeneous group of primary neurodegenerative dementias. Meanwhile, several independent studies have indicated that the Aβ 1-42:Aβ 1-40 ratio is superior to the determination of Aβ 1-42 alone. Currently, several international research initiatives have been launched to further harmonize and optimize preanalytical procedures and CSF-NDD biomarker assays. [ABSTRACT FROM AUTHOR]

Novel diagnostic methods, such as cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) and [18F] amyloid positron emission tomography (PET) are meanwhile recommended for specific indications by international guidelines for the improved early and differential diagnostics of multigenic (sporadic) Alzheimer's dementia (AD). In the case of CSF-NDD the German neuropsychiatric guidelines have already been validated on the S3 level of evidence (http://www.DGPPN.de) and the additional consideration of [18F] amyloid-PET in the current update of the guidelines is to be expected. By means of CSF-NDD and/or [18F] amyloid-PET a predictive diagnosis of incipient (preclinical) AD is also possible for patients at high risk for AD who are in prodromal stages, such as mild cognitive impairment (MCI). As accompanying (secondary) preventive therapy of AD cannot be offered a predictive molecular dementia diagnostics is not recommended by the German neuropsychiatric dementia guidelines (http://www.DGPPN.de). However, novel diagnostic approaches, which offer molecular positive diagnostics of AD have already gained high relevance in therapy research as they allow promising preventive treatment avenues to be validated directly in the clinical trial. Moreover, future blood-based dementia diagnostics by means of multiplex assays is becoming increasingly more feasible; however, so far corresponding proteomic or epigenetic assays could not be consistently validated in independent studies. [ABSTRACT FROM AUTHOR]

As cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) has now been validated at the S3 evidence level, the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the German Society for Neurology (DGN) recommend CSF-NDD in the recent joint dementia guidelines for improved early and differential diagnostics of multigenic (sporadic) Alzheimer's dementia (AD). The CSF-NDD also provides a predictive diagnosis of incipient AD for high-risk patients when they are still in the prodromal stage of mild cognitive impairment (MCI) but as no (secondary) preventive therapy of AD is currently available, the use of CSF-NDD for the predictive molecular diagnosis of AD is not recommended in the neuropsychiatry guidelines (http://www.DGPPN.de). However, molecular diagnostics of preclinical AD by CSF-NDD and/or [18F]-amyloid positron emission tomography (PET) has meanwhile gained high clinical relevance for therapeutic clinical research, as this novel clinical model allows systematic screening for promising (secondary) preventive therapy options. Moreover, it has now become apparent that blood-based neurochemical diagnostics of preclinical and early AD will be possible by means of various formats of multiplex assays. However, so far promising blood assays have not been consistently validated by independent research groups and in contrast to CSF-NDD a blood-based diagnosis of AD is not yet available. [ABSTRACT FROM AUTHOR]

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

Current treatment of Alzheimer’s disease comprises pharmacological therapy and psychosocial interventions for patients and caregivers in the context of a symptom and severity dependent management concept. Treatment is targeted towards the core symptoms of dementia (cognitive and functional deficits) and if necessary, towards the behavioral symptoms of dementia. The treatment of Alzheimer’s dementia with acetylcholine esterase inhibitors (AChE-I; donepezil, galantamine, rivastigmine) and memantine is evidence-based and recommended. For all drugs, the highest tolerable dose should be given. The choice of AChE-I depends on the side-effects and interaction profile, as there is no convincing evidence of a relevant superiority of one of the drugs over another. Mixed dementia should be treated as Alzheimer’s dementia. Treatment of vascular dementia with AChE-I or memantine is off-label and without convincing evidence. There is no convincing evidence for the treatment of frontotemporal dementia or Lewy body dementia. Rivastigmine is effective for the treatment of dementia with Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Neuroimaging is an essential part of the etiological diagnosis of dementia. In this review, techniques that enhance the information extracted from routine magnetic resonance imaging (MRI) are presented. In addition, novel techniques of MR acquisition and analyses are reported that may become part of routine diagnostics in the future. These include automated analysis of structural MRI, proton MR spectroscopy, diffusion tensor imaging, perfusion MRI, and functional MRI. From nuclear medicine, the key techniques of fluorodeoxyglucose positron emission tomography (FDG-PET) and dopamine transporter single photon emission computed tomography (SPECT) for early and differential diagnosis of Alzheimer's dementia and Lewy body dementia and the innovation of amyloid PET are presented. [ABSTRACT FROM AUTHOR]

Summary Dementia with Lewy Bodies (DLB) is the second most common form of dementia in the elderly. Core features of the DLB are fluctuating cognitive symptoms, visual hallucinations and spontaneous parkinsonism. The clinical diagnostic criteria are very useful in the differentiation between DLB and Alzheimer's disease. The deficits in cholinergic neurotransmission are pronounced and associated with cognitive and psychotic symptoms. An 83 years old patient with DLB showed well formed recurrent visual hallucinations and fluctuating cognition and attention. There was no response to treatment with atypical neuroleptics. The patient responded within few days to treatment with Donepezil. Both cognitive and behavioural symptoms were improved significantly. [ABSTRACT FROM AUTHOR]

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