With an established population of elderly subjects with strictly defined mild senile dementia/Alzheimer type (SDAT) and matched healthy elderly controls, we are continuing the longitudinal investigation of the interrelationships and predictive value of clinical, behavioral and multiple biomedical factors. Serial assessments include detailed clinical examinations, psychometric test battery, advanced quantitative CT, EEG, study of event-related potentials (ERP), positron emission tomography (PET), and assay of plasma levels of S-100 protein, a biochemical marker of impaired glial cell integrity. Having found significant differences between mild SDAT subjects and controls on some of these measures, we are starting a prospective study on elderly subjects with cognitive impairment too mild to be diagnosed as SDAT. These subjects and matched controls will be studied by the same measures given above, with the goal of identifying interrelationships and factors which predict the development of SDAT. At a single assessment we will study subjects with mild, moderate and severe SDAT by clinical, psychometric, CT, EEG, and ERP measures. We will compare results from a """"""""cross-sectional"""""""" assessment with those of the longitudinal study. The PET study will describe local cerebral hemodynamics and metabolism in healthy aging and SDAT to explore PET's role in diagnosis and prognosis. Further, it may provide evidence for the role, if and, of brain circulation in pathogenesis of SDAT. We will assess all subjects serially with measures of behavior (activities of daily living, functional capacities) for comparison with our other studies. The longitudinal impact of SDAT on the primary caregiver will also be assessed. The possible relationship between susceptibility to SDAT and HLA antigen frequencies will be examined by HLA study of all subjects. Subjects will be followed until autopsy when results of pathologic examination of the brain will be compared with previous data. Remaining brain tissue will be frozen and stored. These studies have bearing on the enormous national health problem o senile dementia and on the important adaptive capabilities of the healthy elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG003991-02
Application #
3090774
Study Section
Aging Review Committee (AGE)
Project Start
1984-01-01
Project End
1988-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Maxwell, Taylor J; Corcoran, Chris; Del-Aguila, Jorge L et al. (2018) Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels. Alzheimers Res Ther 10:86
Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin et al. (2018) Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 14:205-214
Brainstorm Consortium (see original citation for additional authors) (2018) Analysis of shared heritability in common disorders of the brain. Science 360:
Kinnunen, Kirsi M; Cash, David M; Poole, Teresa et al. (2018) Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study. Alzheimers Dement 14:43-53
Ibanez, Laura; Dube, Umber; Davis, Albert A et al. (2018) Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease. Front Neurosci 12:230
Schultz, Stephanie A; Gordon, Brian A; Mishra, Shruti et al. (2018) Widespread distribution of tauopathy in preclinical Alzheimer's disease. Neurobiol Aging 72:177-185
Broce, Iris; Karch, Celeste M; Wen, Natalie et al. (2018) Correction: Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLoS Med 15:e1002504
Javaherian, Kavon; Newman, Brianne M; Weng, Hua et al. (2018) Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Dis Assoc Disord :
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95
Liao, Fan; Li, Aimin; Xiong, Monica et al. (2018) Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation. J Clin Invest 128:2144-2155

Showing the most recent 10 out of 911 publications