Abstract

Neurochemical and pharmacological studies establish a rationale for clinical trials of drugs that increase central cholinergic activity in patients with a diagnosis of Alzheimer's disease, and in normal elderly people with an age-related loss in memory functioning. The major goal of the project is to test potential cholinomimetic compounds in patients with Alzheimer's disease, normal elderly people with an age-related memory loss and in normal young subjects, to determine the ability of these drugs to enhance memory functioning. Various cholinergic agents with different mechanisms of action will be tested and compared in the same patients to determine their relative abilities to imprve the ability of patients and subjects to learn new information. These drugs include, precursors to acetylcholine, acetylcholinesterase inhibitors and muscarinic receptor agonists. In all instances broad dose ranging studies are a prerequisite to subsequent studies. As these sudies are being conducted, an attempt will be made to determine if the cholinergic deficit that exists in Alzheimer's disease, and exists to a lesser extent in normal elderly people, can be detected in vivo by measurements of cerebrospinal fluid or neuroendocrine parameters.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG002219-08S1
Application #
3090618
Study Section
Aging Review Committee (AGE)
Project Start
1988-04-01
Project End
1989-03-31
Budget Start
1988-04-04
Budget End
1989-03-31
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Khan, Atlas; Liu, Qian; Wang, Kai (2018) iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes. BMC Bioinformatics 19:501
Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen et al. (2018) A Bayesian framework for multiple trait colocalization from summary association statistics. Bioinformatics 34:2538-2545
Toker, Lilah; Mancarci, Burak Ogan; Tripathy, Shreejoy et al. (2018) Transcriptomic Evidence for Alterations in Astrocytes and Parvalbumin Interneurons in Subjects With Bipolar Disorder and Schizophrenia. Biol Psychiatry 84:787-796
Huckins, L M; Hatzikotoulas, K; Southam, L et al. (2018) Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Mol Psychiatry 23:1169-1180
Mitchell, A C; Javidfar, B; Pothula, V et al. (2018) MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Mol Psychiatry 23:123-132
Bryois, Julien; Garrett, Melanie E; Song, Lingyun et al. (2018) Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia. Nat Commun 9:3121
Fazio, Leonardo; Pergola, Giulio; Papalino, Marco et al. (2018) Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory. Proc Natl Acad Sci U S A 115:5582-5587
Gusev, Alexander; Mancuso, Nicholas; Won, Hyejung et al. (2018) Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50:538-548
Girdhar, Kiran; Hoffman, Gabriel E; Jiang, Yan et al. (2018) Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 21:1126-1136
Hauberg, Mads E; Fullard, John F; Zhu, Lingxue et al. (2018) Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls. Mol Psychiatry :

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