Project 3: Memory decline is the earliest manifestation of Alzheimer's disease (AD), and can be detected up to 10 years before the diagnosis is fully established by current methods. Numerous investigations indicate that decline in memory performance with advancing age is common and may occur in the absence of AD. It remains uncertain whether this failure in memory performance reflects a prodromal stage of AD or is a normal variation of aging. Early AD targets the hippocampal formation, a structure comprised of distinct anatomical regions. We have recently developed a functional MR protocol that can detect differential activation of these separate hippocampal, and in a series of pilot studies have found that AD patients have dysfunction in all regions compared to age-matched controls. When we employed this fMRI protocol to study elderly individuals with memory decline, but without dementia, two patterns of hippocampal activation emerged: One pattern had predominant dysfunction in the entorhinal region and was indistinguishable to the pattern seen in AD; and a second pattern had dysfunction restricted to single hippocampal region, the subiculum. The primary goal of this proposal is to determine whether this fMRI protocol can detect a regional pattern of hippocampal dysfunction that is associated with AD, and whether it can reliably dissociate healthy elderly with memory decline into those with and or without prodromal AD. 20 patients with probable AD, 40 elderly with normal with normal memory, and 80 elderly with memory decline will be evaluated at baseline. Elderly with and without memory decline will be followed prospectively and some are predicted to progress to AD at follow-up. Analysis will determine whether elderly with an AD-like hippocampal activation pattern at baseline have different clinical courses and a different incidence of AD. The fMRI protocol will also be employed to identify topographical networks within the hippocampus associated with normal memory processing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
2P50AG008702-11A1
Application #
6344469
Study Section
Special Emphasis Panel (ZAG1-PKN-7 (J1))
Project Start
1989-09-29
Project End
2002-05-31
Budget Start
Budget End
Support Year
11
Fiscal Year
2000
Total Cost
$271,393
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Guerreiro, Rita; Ross, Owen A; Kun-Rodrigues, Celia et al. (2018) Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol 17:64-74
Pottier, Cyril; Zhou, Xiaolai; Perkerson 3rd, Ralph B et al. (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558
Miranda, André M; Lasiecka, Zofia M; Xu, Yimeng et al. (2018) Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. Nat Commun 9:291
Weintraub, Sandra; Besser, Lilah; Dodge, Hiroko H et al. (2018) Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord 32:10-17
Kaur, Antarpreet; Edland, Steven D; Peavy, Guerry M (2018) The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the Detection of Amnestic Mild Cognitive Impairment. Alzheimer Dis Assoc Disord 32:120-124
Wilmoth, Kristin; LoBue, Christian; Clem, Matthew A et al. (2018) Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment. Clin Neuropsychol 32:524-529
Brenowitz, Willa D; Han, Fang; Kukull, Walter A et al. (2018) Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults. Neurobiol Aging 62:64-71
Ting, Simon Kang Seng; Foo, Heidi; Chia, Pei Shi et al. (2018) Dyslexic Characteristics of Chinese-Speaking Semantic Variant of Primary Progressive Aphasia. J Neuropsychiatry Clin Neurosci 30:31-37
Gallagher, Damien; Kiss, Alex; Lanctot, Krista L et al. (2018) Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors. J Clin Psychiatry 80:
Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642

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