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The Impact of Age-Related Changes on Working Memory Functional Activity

This work investigated associations of age-related brain atrophy and functional neural networks identified using multivariate analyses of BOLD fMRI data in young and elder participants (young, N=37; mean age=25; elders, N=15; mean age=74). Two networks were involved in retaining increasing loads of verbal information in working memory. Network utilizations were used to test associations between function and indices of grey matter volume changes using voxel based morphometry. Global changes in brain volume were not associated with the secondary network. Lower regional grey matter volume in the left pre-central gyrus within the primary network was associated with increased secondary network utilization independent of age group. Decreased regional grey matter volume was associated with increased age only in the elders. Increased secondary network expression was associated with increased slope of reaction times across memory load, in the elders. These results support the theory of neural compensation, that elder participants recruit additional neural resources to maintain task performance in the face of age-related decreases in regional grey matter volume.

Department: 
Neurology
Topic: 
Publication type: 
Author: 
Jason Steffener
Adam M. Brickman
Brian C. Rakitin
Yunglin Gazes
Yaakov Stern
Subjects: 
Neurology
Aging
Memory in old age
Magnetic resonance imaging
Title string: 
The Impact of Age-Related Changes on Working Memory Functional Activity
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:j6q573n5wf

Selective Association between Cortical Thickness and Reference Abilities in Normal Aging

A previous study of reference abilities and cortical thickness reported that association between reference abilities and cortical thickness summarized over large ROIs suppressed was suppressed after controlling for mean cortical thickness and global cognition. In this manuscript, we showed that preserving detailed spatial patterns of cortical thickness can identify reference-ability-specific association besides the association explained by global cognition and mean cortical thickness. We identified associations between cortical thickness and 3 cognitive reference abilities after controlling for mean thickness, global cognition, and linear chronological age: (1) memory, (2) perceptual speed, and (3) vocabulary. Global cognition was correlated with mean overall thickness but also was found to have a regionally specific pattern of associations. Nonlinear associations between cortical thickness and cognition were not observed, neither were nonlinear age effects. Age-by-thickness interactions were also absent. This implies that all thickness-cognition relations and age associations are independent of age and that consequently no age range is inherently special, since brain-behavioral findings are invariant across the whole age range.

Department: 
Neurology
Publication type: 
Author: 
Seonjoo Lee
Christian G. Habeck
Qolamreza R. Razlighi
Timothy Salthouse
Yaakov Stern
Subjects: 
Neurosciences
Aging
Cerebral cortex
Cognition--Age factors
Principal components analysis
Title string: 
Selective Association between Cortical Thickness and Reference Abilities in Normal Aging
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:69p8cz8wbr

Regional Cerebral Blood Flow in Mood Disorders. II. Comparison of Major Depression and Alzheimer's Disease

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression,30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and AIzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subproflle Model,developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning.

Department: 
Neurology
Topic: 
UNI: 
Publication type: 
Author: 
Harold A. Sackeim
Isak Prohovnik
James R. Moeller
Richard Paul Mayeux
Yaakov Stern
Devangere P. Devanand
Subjects: 
Neurology
Alzheimer's disease
Cerebral circulation
Depression
Mental
Title string: 
Regional Cerebral Blood Flow in Mood Disorders. II. Comparison of Major Depression and Alzheimer's Disease
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:h44j0zpcbh

Neuropsychological Predictors of Dependency in Patients with Alzheimer Disease

OBJECTIVE: To determine whether specific cognitive deficits can predict the progression of Alzheimer disease (AD). METHODS: Two hundred fifty-two patients with AD enrolled in the Predictors Study were followed at 6-month intervals for up to 4.5 years with neurologic, cognitive, and psychiatric examinations. Neuropsychological functions were assessed by the Modified Mini-Mental State Examination (mMMSE). Items of mMMSE were divided into five cognitive domains: temporospatial orientation, short-term memory, long-term memory, language, and visuoconstructive functions. Loss of autonomy was assessed by both the Dependency Scale (DS) and the Equivalent Institutional Care (EIC) rating. Cox proportional hazards models, adjusted for age, sex, estimated duration of illness at entry into the study, and presence of extrapyramidal signs and behavioral disturbances, were used to determine the predictive value of each neuropsychological domain on dependency outcomes. RESULTS: Global mMMSE, temporospatial orientation, and short-term memory scores were associated with a greater relative risk of moderate or severe dependency. The visuoconstructive score predicted the development of severe dependency. Long-term memory and language scores were not predictive of the EIC or DS endpoints. CONCLUSIONS: The presence of certain neuropsychological deficits at a patient's initial visit, such as short-term memory, temporospatial orientation, and constructive apraxia, predict more rapid dependency in patients with Alzheimer disease. Neuropsychological items have different weights in term of predictive power, and these effects are independent of the influence of age and disease duration at baseline.

Department: 
Neurology
Topic: 
Publication type: 
Author: 
Maria Sarazin
Yaakov Stern
Claudine Berr
Aliza Riba
Marilyn Albert
Jason Brandt
Bruno Dubois
Subjects: 
Neurology
Alzheimer's disease
Cognition
Alzheimer's disease--Forecasting
Title string: 
Neuropsychological Predictors of Dependency in Patients with Alzheimer Disease
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:0gb5mkkwj5

Inter-Rater Reliability of a Clinical Staging of HIV-Associated Cognitive Impairment

Objective: To determine the inter-rater reliability of a modification of the Memorial Sloan-Kettering (MSK) Staging for HIV-associated cognitive impairment. Methods: Data were abstracted on neurologic, neuropsychological, and functional status on 100 individuals participating at four sites in the Northeast AIDS Dementia (NEAD) Consortium cohort study, a longitudinal study of predictors of cognitive impairment in HIV-infected individuals. Neuropsychological performance was defined 1) based on the neuropsychologist’s global impression and 2) solely based on neuropsychological test scores. Raters at each site used the abstracted data to assign an MSK stage to each subject blind to any identifying information. Inter-rater reliability was assessed using kappa statistics. Agreement between computer-generated ratings and site-generated ratings was also assessed. Results: Kappa statistics for pair-wise agreement among the sites regarding MSK stage ranged from 0.70–0.91, representing good to excellent agreement between sites. Agreement between computer-generated ratings and site-generated ratings was in the good to excellent range (0.62–0.79). Conclusions: The authors have modified the MSK rating scale and developed a reliable instrument that can be used in multicenter studies. This instrument will be useful in staging HIV-dementia in future longitudinal studies and will be valuable in increasing accuracy of clinicopathologic studies.

Department: 
Neurology
Topic: 
Publication type: 
Author: 
Karen Marder
Steven M. Albert
Michael P. McDermott
Justin C. McArthur
Giovanni Schifitto
Ola A. Selnes
Ned Sacktor
Yaakov Stern
Donna Palumbo
Karl Kieburtz
Bruce Cohen
Constance Orme
Leon G. Epstein
Subjects: 
Neurology
AIDS dementia complex
Cognition
Reliability
Title string: 
Inter-Rater Reliability of a Clinical Staging of HIV-Associated Cognitive Impairment
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:brv15dv435

Increased Risk of Mortality in Alzheimer's Disease Patients with More Advanced Educational and Occupational Attainment

A reserve hypothesis suggests that clinical symptoms of Alzheimer's disease (AD) begin earlier in individuals with less education. Therefore, patients with less education might survive longer after diagnosis than those with more education. Two hundred forty-six subjects with probable AD were following for 1 to 4 years. There were 78 deaths; 30 deaths occurred in the 127 patients whose education was ≤8 years, while 48 deaths occured in the 119 patients with <8 years of education. Cox proportional hazards models adjusted for age, gender, and clinical dementia rating (CDR) showed that patients with more education had increased mortality (continuous variable: RR = 1.06 for each years of education; 95% confidence interval {CI}, 1.01-1.11; dichotomous variable at 8 yr: RR = 1.76; CI, 1.11-2.77). This observation might at first seem counterintuitve, since groups with lower socioeconomic status are often at greater mortality risk. It implies that at any level of assessed clinical severity, the underlying pathology of AD is more advanced in patients with more education, resulting in shorter duration of diagnosed disease before death. These findings suggest either that education systematically influences global ratings of disease severity or that education provides a reserve against the clinical manifestation of AD pathology.

Department: 
Neurology
UNI: 
Publication type: 
Author: 
Yaakov Stern
Mingxin Tang
Jean Denaro
Richard Paul Mayeux
Subjects: 
Neurology
Alzheimer's disease--Patients
Mortality
Dementia
Education
Title string: 
Increased Risk of Mortality in Alzheimer's Disease Patients with More Advanced Educational and Occupational Attainment
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:h44j0zpcbg

Hippocampal Subregions Differentially Associate with Standardized Memory Tests

Recent studies suggest that individual hippocampal subregions perform distinct cognitive operations and are differentially targeted by aging and disease. Although originally developed to assess global hippocampal function, whether performance on standard memory tests used in neuropsychological batteries is associated with individual hippocampal subregions remains unknown. Here we addressed this issue by imaging 210 neuropsychologically characterized subjects using a high-resolution variant of functional magnetic resonance imaging that generates maps reflective of basal hippocampal metabolism. Regression analysis revealed memory tests that differentially associate with two hippocampal subregions, the entorhinal cortex (EC) and the dentate gyrus (DG). Whereas performance on the delayed retention component of the Selective Reminding Test was associated with the EC, performance on the recognition component of the Benton Visual Retention Test (BVRT) was associated with the DG. Furthermore, elevation in blood glucose, previously shown to target the DG, was found to correlate selectively with the recognition component of the BVRT. These findings provide further evidence that the hippocampal subregions perform distinct roles, and, interpreted in the context of previous neuropsychological and imaging studies, confirm that aging and Alzheimer's disease target different hippocampal subregions.

Department: 
Neurology
Publication type: 
Author: 
Adam M. Brickman
Yaakov Stern
Scott A. Small
Subjects: 
Neurology
Hippocampus (Brain)
Neurosciences
Cognition
Memory--Testing
Title string: 
Hippocampal Subregions Differentially Associate with Standardized Memory Tests
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:bk3j9kd533

Global Familiarity of Visual Stimuli Affects Repetition-Related Neural Plasticity but Not Repetition Priming

In this study, we tested the prediction of the component process model of priming [Henson, R.N. (2003). Neuroimaging studies of priming. Prog Neurobiol, 70 (1), 53-81] that repetition priming of familiar and unfamiliar objects produces qualitatively different neural repetition effects. In an fMRI study, subjects viewed four repetitions of familiar objects and globally unfamiliar objects with familiar components. Reliable behavioral priming occurred for both item types across the four presentations and was of a similar magnitude for both stimulus types. The imaging data were analyzed using multivariate linear modeling, which permits explicit testing of the hypothesis that the repetition effects for familiar and unfamiliar objects are qualitatively different (i.e., non-scaled versions of one another). The results showed the presence of two qualitatively different latent spatial patterns of repetition effects from presentation 1 to presentation 4 for familiar and unfamiliar objects, indicating that familiarity with an object's global structural, semantic, or lexical features is an important factor in priming-related neural plasticity. The first latent spatial pattern strongly weighted regions with a similar repetition effect for both item types. The second pattern strongly weighted regions contributing a repetition suppression effect for the familiar objects and repetition enhancement for the unfamiliar objects, particularly the posterior insula, superior temporal gyrus, precentral gyrus, and cingulate cortex. This differential repetition effect might reflect the formation of novel memory representations for the unfamiliar items, which already exist for the familiar objects, consistent with the component process model of priming.

Department: 
Neurology
Publication type: 
Author: 
Anja Soldan
Eric Zarahn
John Hilton
Yaakov Stern
Subjects: 
Neurosciences
Priming (Psychology)
Brain--Imaging
Magnetic resonance imaging
Neuroplasticity
Title string: 
Global Familiarity of Visual Stimuli Affects Repetition-Related Neural Plasticity but Not Repetition Priming
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:s1rn8pk0rq

Epidemiology of Alzheimer Disease

The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease.

Department: 
Neurology
Topic: 
UNI: 
Publication type: 
Author: 
Richard Paul Mayeux
Yaakov Stern
Subjects: 
Neurology
Alzheimer's disease
Epidemiology
Dementia
Title string: 
Epidemiology of Alzheimer Disease
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:nk98sf7m2s

Differing Effects of Education on Cognitive Decline in Diverse Elders with Low Versus High Educational Attainment

OBJECTIVE: In light of growing debate over whether and how early life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. METHOD: Older adults (N = 3,435) in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. RESULTS: More years of education were associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. Although having additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. CONCLUSIONS: Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., 9 years and beyond) is associated with higher income, which may influence late-life cognitive health through multiple, nonmutually exclusive pathways.

Department: 
Neurology
Publication type: 
Author: 
Laura B. Zahodne
Yaakov Stern
Jennifer J. Manly
Subjects: 
Neuropsychology
Cognition--Age factors
Education
Aging
Title string: 
Differing Effects of Education on Cognitive Decline in Diverse Elders with Low Versus High Educational Attainment
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:15dv41ns2p

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