TY - JOUR T1 - FASTKD2 is associated with memory and hippocampal structure in older adults. JF - Mol Psychiatry Y1 - 2015 A1 - Vijay K Ramanan A1 - Nho, Kwangsik A1 - Shen, Li A1 - Shannon L Risacher A1 - Brenna C McDonald A1 - Martin R Farlow A1 - Tatiana Foroud A1 - Gao, Sujuan A1 - Soininen, Hilkka A1 - Kloszewska, Iwona A1 - Mecocci, Patrizia A1 - Tsolaki, Magda A1 - Vellas, Bruno A1 - Lovestone, Simon A1 - Aisen, Paul S. A1 - Ronald C Petersen A1 - Jack, Clifford R. A1 - Shaw, Leslie M. A1 - Trojanowski, John Q. A1 - Weiner, Michael W. A1 - Green, Robert C. A1 - Arthur W. Toga A1 - Philip L de Jager A1 - Lei Yu A1 - David A Bennett A1 - Andrew J Saykin KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Alzheimer disease KW - Female KW - Genetic Association Studies KW - Genome-Wide Association Study KW - Hippocampus KW - Humans KW - Longitudinal Studies KW - Male KW - Memory KW - Memory Disorders KW - Polymorphism, Single Nucleotide KW - Protein-Serine-Threonine Kinases KW - Structure-Activity Relationship AB -

Memory impairment is the cardinal early feature of Alzheimer's disease, a highly prevalent disorder whose causes remain only partially understood. To identify novel genetic predictors, we used an integrative genomics approach to perform the largest study to date of human memory (n=14 781). Using a genome-wide screen, we discovered a novel association of a polymorphism in the pro-apoptotic gene FASTKD2 (fas-activated serine/threonine kinase domains 2; rs7594645-G) with better memory performance and replicated this finding in independent samples. Consistent with a neuroprotective effect, rs7594645-G carriers exhibited increased hippocampal volume and gray matter density and decreased cerebrospinal fluid levels of apoptotic mediators. The MTOR (mechanistic target of rapamycin) gene and pathways related to endocytosis, cholinergic neurotransmission, epidermal growth factor receptor signaling and immune regulation, among others, also displayed association with memory. These findings nominate FASTKD2 as a target for modulating neurodegeneration and suggest potential mechanisms for therapies to combat memory loss in normal cognitive aging and dementia.

PB - 20 VL - 20 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25385369?dopt=Abstract U2 - PMC4427556 U4 - Genetic analysis/Alzheimer disease/Memory impairment/predictors/FASTKD2 ER - TY - JOUR T1 - Operationalizing diagnostic criteria for Alzheimer's disease and other age-related cognitive impairment-Part 2. JF - Alzheimers Dement Y1 - 2011 A1 - Seshadri, Sudha A1 - Alexa S. Beiser A1 - Au, Rhoda A1 - Philip A Wolf A1 - Robert S Wilson A1 - Ronald C Petersen A1 - David S Knopman A1 - Walter A Rocca A1 - Claudia H Kawas A1 - Maria M Corrada A1 - Brenda L Plassman A1 - Kenneth M. Langa A1 - Helena C Chui KW - Age Factors KW - Aging KW - Alzheimer disease KW - Cognition Disorders KW - Community Health Planning KW - Humans KW - Incidence KW - Longitudinal Studies KW - Neuropsychological tests KW - Prevalence KW - United States AB -

This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment and/or dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor determining prevalence estimates of Alzheimer's disease (AD) is the severity of cognitive impairment used as a threshold to define cases. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than the studies aimed at identifying persons in the earliest stages of AD. There are limited autopsy data from the aforementioned epidemiological studies to address accuracy in the diagnosis of etiological subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment and also some persons without dementia or mild cognitive impairment meet pathological criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies.

PB - 7 VL - 7 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21255742?dopt=Abstract U2 - PMC3039838 U4 - Alzheimer disease/cognitive Impairment/PREVALENCE/Incidence/Dementia ER - TY - JOUR T1 - Trends in the incidence and prevalence of Alzheimer's disease, dementia, and cognitive impairment in the United States. JF - Alzheimers Dement Y1 - 2011 A1 - Walter A Rocca A1 - Ronald C Petersen A1 - David S Knopman A1 - Liesi Hebert A1 - Denis A Evans A1 - Kathleen S Hall A1 - Gao, Sujuan A1 - Frederick W Unverzagt A1 - Kenneth M. Langa A1 - Eric B Larson A1 - Lon R White KW - Age Factors KW - Alzheimer disease KW - Cognition Disorders KW - Cohort Studies KW - Community Health Planning KW - Dementia KW - Humans KW - Incidence KW - Prevalence KW - Residence Characteristics KW - Retrospective Studies KW - Time Factors KW - United States AB -

Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age-specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community-based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.

PB - 7 VL - 7 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21255746?dopt=Abstract U2 - PMC3026476 U4 - Alzheimers disease/Dementia/Cognitive impairment/Prevalence/Incidence/Time trends ER -