BACKGROUND: To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI). METHODS: Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed. RESULTS: Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time. CONCLUSIONS: This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.

• Klíčová slova
• Alzheimer’s disease, Cognition, Dementia, Longitudinal changes, Mild behavioral impairment,
• MeSH
• epizodická paměť * MeSH
• exekutivní funkce MeSH
• kognice MeSH
• kognitivní dysfunkce * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• průřezové studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

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.

• MeSH
• Alzheimerova nemoc * genetika   patologie   MeSH
• celogenomová asociační studie MeSH
• kognitivní dysfunkce * psychologie   MeSH
• lidé MeSH
• proteiny tau genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• proteiny tau MeSH

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

• MeSH
• celogenomová asociační studie MeSH
• duševní poruchy klasifikace   diagnóza   genetika   MeSH
• fenotyp MeSH
• genetická variace MeSH
• kvantitativní znak dědičný MeSH
• lidé MeSH
• nemoci mozku klasifikace   diagnóza   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH