@article {8326, title = {FASTKD2 is associated with memory and hippocampal structure in older adults.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 Oct}, pages = {1197-204}, publisher = {20}, abstract = {

Memory impairment is the cardinal early feature of Alzheimer{\textquoteright}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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer disease, Female, Genetic Association Studies, Genome-Wide Association Study, Hippocampus, Humans, Longitudinal Studies, Male, Memory, Memory Disorders, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases, Structure-Activity Relationship}, issn = {1476-5578}, doi = {10.1038/mp.2014.142}, author = {Vijay K Ramanan and Nho, Kwangsik and Shen, Li and Shannon L Risacher and Brenna C McDonald and Martin R Farlow and Tatiana Foroud and Gao, Sujuan and Soininen, Hilkka and Kloszewska, Iwona and Mecocci, Patrizia and Tsolaki, Magda and Vellas, Bruno and Lovestone, Simon and Aisen, Paul S. and Ronald C Petersen and Jack, Clifford R. and Shaw, Leslie M. and Trojanowski, John Q. and Weiner, Michael W. and Green, Robert C. and Arthur W. Toga and Philip L de Jager and Lei Yu and David A Bennett and Andrew J Saykin} } @article {7563, title = {Operationalizing diagnostic criteria for Alzheimer{\textquoteright}s disease and other age-related cognitive impairment-Part 2.}, journal = {Alzheimers Dement}, volume = {7}, year = {2011}, month = {2011 Jan}, pages = {35-52}, publisher = {7}, abstract = {

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{\textquoteright}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.

}, keywords = {Age Factors, Aging, Alzheimer disease, Cognition Disorders, Community Health Planning, Humans, Incidence, Longitudinal Studies, Neuropsychological tests, Prevalence, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.12.002}, author = {Seshadri, Sudha and Alexa S. Beiser and Au, Rhoda and Philip A Wolf and Robert S Wilson and Ronald C Petersen and David S Knopman and Walter A Rocca and Claudia H Kawas and Maria M Corrada and Brenda L Plassman and Kenneth M. Langa and Helena C Chui} } @article {7567, title = {Trends in the incidence and prevalence of Alzheimer{\textquoteright}s disease, dementia, and cognitive impairment in the United States.}, journal = {Alzheimers Dement}, volume = {7}, year = {2011}, month = {2011 Jan}, pages = {80-93}, publisher = {7}, abstract = {

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.

}, keywords = {Age Factors, Alzheimer disease, Cognition Disorders, Cohort Studies, Community Health Planning, Dementia, Humans, Incidence, Prevalence, Residence Characteristics, Retrospective Studies, Time Factors, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.11.002}, author = {Walter A Rocca and Ronald C Petersen and David S Knopman and Liesi Hebert and Denis A Evans and Kathleen S Hall and Gao, Sujuan and Frederick W Unverzagt and Kenneth M. Langa and Eric B Larson and Lon R White} }