Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six-subtest battery for the bedside screening of a global executive dysfunction; although recently devised, it is already extensively used thanks to its ease of administration and claimed sensitivity. The aim of the present study was to derive Italian normative values from a sample of 364 control subjects (215 women and 149 men) of different ages (mean: 57.4+/-17.9 years; range: 20-94 years) and educational level (mean: 10.4+/-4.3 years; range: 1-17 years); the Mini Mental State Examination (MMSE) was concurrently administered. Multiple linear regression analysis revealed significant effects for age and education whereas gender was not significant; thus, from the derived linear equation, a correction grid for FAB raw scores was built. Based on nonparametric techniques, inferential cut-off scores were subsequently determined and equivalent scores (ES) computed. Test-restest and interrater reliabilities were both satisfactory. Interestingly, MMSE was significantly correlated with FAB raw scores, whereas adjusted scores were not. The present data may improve the accuracy in the use of the FAB both for clinical and research purposes.

Autoimmune diseases following collection(s): This article, along with others on similar topics, appears in the Permissions & Licensing http://nn.neurology.org/misc/about.xhtml#permissions its entirety can be found online at: Information about reproducing this article in parts (figures,tables) or in Reprints http://nn.neurology.org/misc/addir.xhtml#reprintsus Information about ordering reprints can be found online: Academy of Neurology.. All rights reserved. Online

The quality of life of community-dwelling elderly people is significantly linked to sensory impairment, which can be detected through simple physical examination. Mood level and social relationships are particularly affected by visual impairment, whereas self-sufficiency in daily living is more strongly related to hearing impairment.