Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

Introduction: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia. Methods: The databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review. Results: In 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer’s disease and healthy controls. Conclusion: IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer

Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer’s Disease in the European Prospective DESCRIPA Study

Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e. g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE >= 28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (A beta(42), t-tau, APOE epsilon 4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright (C) 2013 S. Karger AG, Base

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Konstruktion und Evaluation der dritten Version des Skalensystems zur Erfassung des Umweltbewusstseins (SEU-3)

'Das Skalensystem zur Erfassung des Umweltbewusstseins (SEU) wurden hinsichtlich des Itempools und in Bezug auf die erfassten Dimensionen ueberarbeitet und in mehreren Untersuchungen evaluiert; der Konstruktionsansatz basierte auf der klassischen Testtheorie. Das ueberarbeitete SEU behaelt das bewaehrte facettentheoretische Konzept der Vorgaengerversionen mit einer konzeptuellen und einer inhaltlichen Ebene bei, jedoch wurden die erfassten Dimensionen aufgrund frueherer Befunde veraendert. Ferner wurden eine Globalskala sowie vier verschiedene, ebenfalls eindimensionale Kurzversionen der Globalskala konstruiert und einer Qualitaetspruefung unterzogen. Basierend auf den Fragebogendaten mehrerer Stichproben (n=12 psychologische und n=22 Umweltexperten; n=104 Mitglieder in Umweltschutzorganisationen; Vergleichsstichprobe nicht engagierter Personen, n=203; vorwiegend studentische Stichprobe, n=64 mit jeweils drei Fremdeinschaetzungen pro Vpn) wurden Homogenitaet, Retest-Reliabilitaet nach ca. 5 1/2 Wochen, korrelative Struktur und verschiedene Validitaetsindikatoren erhoben. Die Ergebnisse sprechen fuer eine gute Qualitaet der Skalen und dokumentieren ihre Brauchbarkeit fuer Forschungszwecke. Die besten Werte erreichte die auf Basis der Uebereinstimmung zwischen Selbst-und Fremdbeurteilung konstruierte, aus 21 Items bestehende Globalskala UGK-V. Auf der Aggregatebene war es ferner moeglich, betraechtliche Anteile der Varianz der Stichproben-Mittelwerte der SEU-Items ueber von Experten erhobene Bewertungen der Item-Charakteristika aufzuklaeren.' (Autorenreferat)'Describes the revision (itempool and dimensions) and evaluation of a set of (German language) scales for assessing individual environmental attitudes, behavioral intentions and self-reported behavior. Besides belonging to one of these three scales, each item belongs to one of seven scales measuring environmentally relevant content areas (facet-approach). The revision was carried out according to the principles of the classical approach of test-construction. Furthermore, a global scale and four different, unidimensional short forms of the global scale were constructed. Results are presented using questionnaire responses from various samples (n=12 psychological and n=22 environmental experts, n=104 subjects who belong to conservation groups; n=203 subjects who do not belong to conservation groups; n=64 students with three peer-ratings for each subject; each sample comprised German female and male adults). Homogeneity, retest-reliability over approx. 5.5 weeks, correlations among scales and different indicators of validity are reported. These results demonstrate the quality of the constructed scales and indicate their usefulness for purposes of scientific research. The best scale according to the various indicators was a global, 21-item scale whose selection criterion had been the correlation between self- and peer-ratings. Furthermore, on an aggregate level, it was possible to explain significant proportions of the variance of item means in our various samples by using expert ratings of item characteristics.' (author's abstract)SIGLEAvailable from UuStB Koeln(38)-990106349 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.

peer reviewedFrontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology

Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.

Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.This article is freely available via PubMed Central. Click on the 'Additional Link' above to access the full text