@article {9747, title = {Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies}, journal = {Neurobiology of Aging}, volume = {69}, year = {2018}, month = {Jan-09-2018}, pages = {111 - 116}, abstract = {To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations. One standard deviation increase of TL was associated with 0.021 unit increase (95\% confidence interval [CI]: 0.001, 0.042) of standardized mean general cognitive ability. After controlling for sex, the point estimate remained similar (0.019) with a wider CI (95\% CI: 0.002, 0.039). The association was attenuated with adjustment for educational attainment (0.009, 95\% CI: 0.009, 0.028). No strong evidence was observed for the association of TL and decline in general cognitive ability. Longer TL was associated with higher general cognitive ability levels in the age-adjusted models but not in the models including all covariates, nor with cognitive decline.}, keywords = {Cognitive Ability, Gender Differences, Telomeres}, issn = {01974580}, doi = {10.1016/j.neurobiolaging.2018.05.004}, url = {https://linkinghub.elsevier.com/retrieve/pii/S019745801830160Xhttps://api.elsevier.com/content/article/PII:S019745801830160X?httpAccept=text/xmlhttps://api.elsevier.com/content/article/PII:S019745801830160X?httpAccept=text/plain}, author = {Zhan, Yiqiang and Clements, Mark S. and Rosebud O. Roberts and Vassilaki, Maria and Druliner, Brooke R. and Boardman, Lisa A. and Ronald C Petersen and Chandra A Reynolds and Nancy L Pedersen and H{\"a}gg, Sara} } @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 {8605, title = {The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer{\textquoteright}s dementia: findings from a nationally representative study.}, journal = {Neuropsychology}, volume = {27}, year = {2013}, month = {2013 Jan}, pages = {86-94}, abstract = {

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer{\textquoteright}s dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers.

METHOD: The frequency of the ε4 allele was studied in older adults (mean age > 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging{\textquoteright}s Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set.

RESULTS: Epsilon 4 increased the rate of progression from normal functioning to MCI (58\% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4.

CONCLUSIONS: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Apolipoproteins E, Cognitive Dysfunction, disease progression, Female, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Logistic Models, Longitudinal Studies, Male, National Institutes of Health (U.S.), Neuropsychological tests, Risk Factors, United States}, issn = {1931-1559}, doi = {10.1037/a0030855}, url = {http://psycnet.apa.org/journals/neu/27/1/86/}, author = {Brainerd, C. J. and V. F. Reyna and Ronald C Petersen and Glenn E Smith and Kenney, A. E. and C. J. Gross and Taub, E. S. and Brenda L Plassman and Gwenith G Fisher} } @article {7671, title = {Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.}, journal = {Neuropsychology}, volume = {25}, year = {2011}, note = {Brainerd, Charles J Reyna, Valerie F Petersen, Ronald C Smith, Glenn E Taub, Emily S 1RC1AG036915-01/AG/NIA NIH HHS/United States U01AG009740/AG/NIA NIH HHS/United States Research Support, N.I.H., Extramural United States Neuropsychology. 2011 Nov;25(6):679-89.}, month = {2011 Nov}, pages = {679-89}, publisher = {25}, abstract = {

OBJECTIVE: Although the ε4 allele of the apolipoprotein E (APOE) genotype is a known risk factor for Alzheimer{\textquoteright}s dementia (AD), prior findings on whether it is also a risk factor for mild cognitive impairment (MCI) have been inconsistent. We tested two contrasting explanations: (a) an ε4-AD specificity hypothesis, and (b) a measurement insensitivity hypothesis.

METHOD: The frequency of the ε4 allele was investigated in older adults (mean age > 70) with various types of cognitive impairment (including MCI) and various types of dementia (including AD) with the aging, demographics, and memory study (ADAMS) of the National Institute on Aging{\textquoteright}s Health and Retirement Study (HRS). The ADAMS controls sources of Type I and Type II error that are posited in the ε4-AD specificity hypothesis and the measurement insensitivity hypothesis, and it is the only nationally representative data set on aging and cognitive impairment.

RESULTS: ε4 was a reliable predictor of MCI, with a frequency of 32\% in MCI subjects versus 20\% in healthy control subjects. This link was specific to MCI because ε4 was not a risk factor for other forms of cognitive impairment without dementia.

CONCLUSIONS: The results support the measurement insensitivity hypothesis rather than the ε4-AD specificity hypothesis and are consistent with recent research showing modest reductions in cognitive performance among normal functioning ε4 carriers.

}, keywords = {Aged, Aged, 80 and over, Aging, Analysis of Variance, Apolipoprotein E4, Cognitive Dysfunction, Dementia, Female, Gene Frequency, Genetic Markers, Genetic Testing, Genotype, Humans, Male, National Institute on Aging (U.S.), Neuropsychological tests, Reference Values, Reproducibility of Results, Risk Factors, United States}, issn = {1931-1559}, doi = {10.1037/a0024483}, author = {Brainerd, Charles J and V. F. Reyna and Ronald C Petersen and Glenn E Smith and Taub, Emily S} } @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} }