Patients with Parkinson's disease (PD) have rigidity, bradykinesia, resting tremor and gait disturbance. These same signs may also be present to a mild degree in many normal elderly individuals who do not qualify for a diagnosis of PD, (i.e., mild Parkinsonian signs [MPS]). MPS are present in 30 - 40% of normal elderly individuals, are associated with a two-fold increased risk of mortality, and are an early marker for incident Alzheimer's disease (AD). A parallel may be drawn between MPS and mild cognitive impairment (MCI), as both entities may represent markers for incident AD. Whereas MCI has been the subject of intense investigation, MPS has received little attention. As a consequence, there are many unanswered questions about MPS. First, only a fraction of the individuals with MPS develop incident AD mad it is not clear why some individuals with MPS go on to develop AD while others do not. How this relates to known risk factors for AD has not been studied. Second, what are the long-term functional consequences of MPS? Third, what is the neuro-anatomical basis for MPS and is there evidence of basal ganglia involvement? There are no neuro-imaging data comparing individuals with MPS to similarly-aged individuals without MPS. This study will utilize the WHICAP II cohort. Primary Aim 1 is to study the relationship between MPS and risk factors for AD in increasing the risk for AD. Risk factors for AD that were assessed at baseline were: age, gender, family history of dementia, history of head injury, education, estrogen use, and APOE status. We hypothesize that subjects that have MPS as well as other baseline AD risk factors will be at the greatest risk for incident AD during follow-up. Primary Aim 2 is to study the functional impact of MPS in a longitudinal setting. We hypothesize that the subjects with MPS at baseline, and especially abnormalities in the axial function domain at baseline, will demonstrate more rapid decline in function during follow-up and that the rate of change in MPS will be associated with the rate of change in function. Primary Aim 3 is to study the neuroanatomical basis for MPS using magnetic resonance imaging (MRI) in 1000 non-demented subjects who will be scanned at Time 2. We hypothesize that subjects with MPS will demonstrate a reduction in MRI-assessed metabolic activity in the basal ganglia when compared with subjects without MPS and that subjects with MPS and a reduction of metabolic activity in the basal ganglia will be at increased risk for incident AD compared with subjects with neither MPS nor a reduction in metabolic activity. As our ability to treat dementia improves, there will be a corresponding increase in our interest in identifying individuals with MPS and in understanding this entity and its relationship to dementia. In this proposal, we set forth three research aims that will address basic unknowns about MPS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG007232-19
Application #
7459740
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
19
Fiscal Year
2007
Total Cost
$89,143
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Zahodne, Laura B; Watson, Caitlin W-M; Seehra, Sonia et al. (2018) Positive Psychosocial Factors and Cognition in Ethnically Diverse Older Adults. J Int Neuropsychol Soc 24:294-304
Zahodne, Laura B; Schupf, Nicole; Brickman, Adam M (2018) Control beliefs are associated with preserved memory function in the face of low hippocampal volume among diverse older adults. Brain Imaging Behav 12:1112-1120
Rizvi, Batool; Narkhede, Atul; Last, Briana S et al. (2018) The effect of white matter hyperintensities on cognition is mediated by cortical atrophy. Neurobiol Aging 64:25-32
Winawer, Melodie R; Griffin, Nicole G; Samanamud, Jorge et al. (2018) Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy. Ann Neurol 83:1133-1146
Gu, Yian; Manly, Jennifer J; Mayeux, Richard P et al. (2018) An Inflammation-related Nutrient Pattern is Associated with Both Brain and Cognitive Measures in a Multiethnic Elderly Population. Curr Alzheimer Res 15:493-501
Reitz, Christiane; Guzman, Vanessa A; Narkhede, Atul et al. (2017) Relation of Dysglycemia to Structural Brain Changes in a Multiethnic Elderly Cohort. J Am Geriatr Soc 65:277-285
Noble, James M; Schupf, Nicole; Manly, Jennifer J et al. (2017) Secular Trends in the Incidence of Dementia in a Multi-Ethnic Community. J Alzheimers Dis 60:1065-1075
Last, Briana S; García Rubio, Maria-José; Zhu, Carolyn W et al. (2017) Medicare Expenditure Correlates of Atrophy and Cerebrovascular Disease in Older Adults. Exp Aging Res 43:149-160
Gu, Yian; Vorburger, Robert; Scarmeas, Nikolaos et al. (2017) Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population. Brain Behav Immun 65:150-160
Sachdev, Perminder S; Lo, Jessica W; Crawford, John D et al. (2017) STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease. Alzheimers Dement (Amst) 7:11-23

Showing the most recent 10 out of 440 publications