Multidimensional assessment of challenging behaviors in advanced stages of dementia in nursing homes-The insideDEM framework.

Introduction: Assessment of challenging behaviors in dementia is important for intervention selection. Here, we describe the technical and experimental setup and the feasibility of long-term multidimensional behavior assessment of people with dementia living in nursing homes.

Methods: We conducted 4 weeks of multimodal sensor assessment together with real-time observation of 17 residents with moderate to very severe dementia in two nursing care units.

Translation of imaging biomarkers from clinical research to healthcare.

The use of biomarkers for diagnostics of Alzheimer's disease (AD) has increased over the last years in specialized care and experimental settings. With the possibly upcoming availability of disease-modifying therapeutic agents, the diagnostics and treatment of patients with cognitive impairment will change. Biomarkers will be used as theranostic markers for case finding.

Does Functional Connectivity Provide a Marker for Cognitive Rehabilitation Effects in Alzheimer's Disease? An Interventional Study.

Background: Cognitive rehabilitation (CR) is a cognitive intervention for patients with Alzheimer's disease (AD) that aims to maintain everyday competences. The analysis of functional connectivity (FC) in resting-state functional MRI has been used to investigate the effects of cognitive interventions.

Objectives: We evaluated the effect of CR on the default mode network FC in a group of patients with mild AD, compared to an active control group.

Cognitive Rehabilitation in Alzheimer's Disease: A Controlled Intervention Trial.

Background: Cognitive Rehabilitation for Alzheimer's disease (AD) is an integrative multimodal intervention. It aims to maintain autonomy and quality of life by enhancing the patients' abilities to compensate for decreased cognitive functioning.

Objective: We evaluated the feasibility of a group-based Cognitive Rehabilitation approach in mild AD dementia and assessed its effect on activities of daily living (ADL).

White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia.

Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND.

Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer's disease.

Introduction: We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL-40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II).

Methods: YKL-40 was compared among HCs (n = 21), mild cognitive impairment (n = 41), AD (n = 35), and FTD (n = 9) (level I) and among HCs (n = 21), AD pathophysiology (tau and amyloid β) negative (n = 15), tau positive (n = 15), amyloid β positive (n = 13), AD pathophysiology positive (n = 33), and FTD (n = 9) (level II).

Results: Level I: YKL-40 discriminated AD from HC and FTD (area under the receiver operating characteristic curves [AUROCs] = 0.

Multicenter stability of resting state fMRI in the detection of Alzheimer's disease and amnestic MCI.

Background: In monocentric studies, patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia exhibited alterations of functional cortical connectivity in resting-state functional MRI (rs-fMRI) analyses. Multicenter studies provide access to large sample sizes, but rs-fMRI may be particularly sensitive to multiscanner effects.

Methods: We used data from five centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.

Reduced Cholinergic Basal Forebrain Integrity Links Neonatal Complications and Adult Cognitive Deficits After Premature Birth.

Background: Prematurely born individuals have an increased risk for long-term neurocognitive impairments. In animal models, development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that cBF integrity is impaired in prematurely born individuals and mediates adult cognitive impairments associated with prematurity.

Is the left uncinate fasciculus associated with verbal fluency decline in mild Alzheimer's disease?

The association between verbal fluency deficit in Alzheimer's disease (AD) and deterioration of specific white matter (WM) tracts is currently not well understood. Using diffusion tensor imaging, we investigated a possible association between the left uncinate fasciculus, which has been implicated in word retrieval, and verbal fluency deficit in AD. A comparison of five properties of WM (fractional anisotropy, mode of anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) in 28 mild AD patients and 26 age-, gender- and education-matched healthy controls revealed significant group differences in a range of WM tracts.

Robust Detection of Impaired Resting State Functional Connectivity Networks in Alzheimer's Disease Using Elastic Net Regularized Regression.

The large number of multicollinear regional features that are provided by resting state (rs) fMRI data requires robust feature selection to uncover consistent networks of functional disconnection in Alzheimer's disease (AD). Here, we compared elastic net regularized and classical stepwise logistic regression in respect to consistency of feature selection and diagnostic accuracy using rs-fMRI data from four centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.org), comprising 53 AD patients and 118 age and sex matched healthy controls.

PETPVE12: an SPM toolbox for Partial Volume Effects correction in brain PET - Application to amyloid imaging with AV45-PET.

Positron emission tomography (PET) allows detecting molecular brain changes in vivo. However, the accuracy of PET is limited by partial volume effects (PVE) that affects quantitative analysis and visual interpretation of the images. Although PVE-correction methods have been shown to effectively increase the correspondence of the measured signal with the true regional tracer uptake, these procedures are still not commonly applied, neither in clinical nor in research settings.

Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI.

Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance.

Hippocampus and Basal Forebrain Volumetry for Dementia and Mild Cognitive Impairment Diagnosis: Could It Be Useful in Primary Care?

Background: Once a patient or a knowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations.

Objective: To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as a proxy for cerebrovascular comorbidity on diagnostic accuracy.

The Primacy Effect in Amnestic Mild Cognitive Impairment: Associations with Hippocampal Functional Connectivity.

The "primacy effect," i.e., increased memory recall for the first items of a series compared to the following items, is reduced in amnestic mild cognitive impairment (aMCI).

Neuronal correlates of serial position performance in amnestic mild cognitive impairment.

Objectives: 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).

Potentially Inappropriate Medication in Community-Dwelling Primary Care Patients who were Screened Positive for Dementia.

Background: Potentially inappropriate medication (PIM) in older people is a risk factor for adverse drug effects. This risk is even higher in older people with dementia (PWD).

Objective: Our study aimed to determine (1) the prevalence of PIM among primary care patients who were screened positive for dementia and (2) the sociodemographic and clinical variables associated with the use of PIM.

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants.

Applied multimodal diagnostics in a case of presenile dementia.

Background: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The possibility of disease-modifying strategies has evoked a need for early and accurate diagnosis. To improve the accuracy of the clinical diagnosis of AD, biomarkers like cerebrospinal fluid (CSF) and neuroimaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) have been incorporated into the diagnostic guidelines of AD.

TDP-43 pathology and cognition in ALS: A prospective clinicopathologic correlation study.

Objective: Although a systematic spread of pathologic TDP-43 expression throughout the CNS in amyotrophic lateral sclerosis (ALS) has been proposed, the relationship between cognition and the extent and neuroanatomic distribution of TDP-43 pathology has not received considerable attention.

Methods: We investigated the association between cognitive functioning and the extent of TDP-43 pathology in postmortem CNS tissue from 18 patients with ALS stratified into 3 groups based on detailed prospective neuropsychological testing (cognitively not impaired, n = 6; cognitively impaired, n = 6; ALS- frontotemporal dementia [FTD], n = 6) and analyzed these cases for clinicopathologic correlations.

Results: Our findings demonstrate a close relationship between cognition and the extent of TDP-43 pathology in non-primary motor areas with a striking difference between ALS-FTD and the 2 other cognitive groups.

Hearing Impairment Affects Dementia Incidence. An Analysis Based on Longitudinal Health Claims Data in Germany.

Recent research has revealed an association between hearing impairment and dementia. The objective of this study is to determine the effect of hearing impairment on dementia incidence in a longitudinal study, and whether ear, nose, and throat (ENT) specialist care, care level, institutionalization, or depression mediates or moderates this pathway. The present study used a longitudinal sample of 154,783 persons aged 65 and older from claims data of the largest German health insurer; containing 14,602 incident dementia diagnoses between 2006 and 2010.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease.

Hippocampal volume and integrity as predictors of cognitive decline in intact elderly.

The risk of Alzheimer's disease can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus with a novel measure of hippocampal integrity (HI) derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 years or older at baseline, and were tested twice, roughly 3 years apart.

Hippocampus and basal forebrain volumes modulate effects of anticholinergic treatment on delayed recall in healthy older adults.

Introduction: Volumes of hippocampus and cholinergic basal forebrain are associated with delayed recall performance and may modulate the effect of a muscarinic receptor antagonist on delayed recall in healthy volunteers.

Methods: We studied 15 older adults before and after the oral administration of a single dose of 1 or 2 mg of the preferential M1 muscarinic receptor antagonist trihexyphenidyl (Artane™) or placebo in a double-blind randomized cross-over design. Hippocampus and basal forebrain volumes were measured using magnetic resonance imaging.

Subjective memory impairment: No suitable criteria for case-finding of dementia in primary care.

Introduction: Subjective memory impairment (SMI) might be used for the case-finding of dementia. Present analyses aim to determine the diagnostic value and the predictive ability of SMI and related worries for the discrimination of patients screened positive or negative for dementia.

Methods: The analyses are based on data derived from the ongoing German general practioner (GP)-based, randomized controlled trial DelpHi-MV.

Association Between Smoking and Cholinergic Basal Forebrain Volume in Healthy Aging and Prodromal and Dementia Stages of Alzheimer's Disease.

Background: Smoking has been found associated with decreased cerebral volumes in healthy adults and in various neuropsychiatric disorders.

Objective: We aimed to determine whether chronic nicotine exposure through smoking is associated with reduced volume of cortically projecting cholinergic basal forebrain nuclei in healthy aging, mild cognitive impairment (MCI), and dementia stages of Alzheimer's disease (AD).

Methods: We retrieved cross-sectional data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database including 179 cognitively normal elderly subjects, 270 subjects with early stage MCI, 136 subjects in later, more advanced, stage of MCI, and 86 subjects in dementia stages of AD.