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RISK FACTORS FOR PATHOLOGIC MARKERS OF PARKINSON DISEASE

Award Number: R01NS041265
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2000
PERIOD OF PERFORMANCE END DATE: 05/31/2012

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RISK FACTORS FOR PATHOLOGIC MARKERS OF PARKINSON DISEASE - DESCRIPTION (provided by applicant): The purpose of this continuation application is to further study two neuropathologic markers of Parkinson's disease (PD), neuronal loss in the substantia niqra (SN) and diminished striatal dopamine levels, in brains of Japanese-American male decedents who were participants in the population based Honolulu Heart Program/Honolulu-Asia Aging Study. These are used as continuous endpoints to identify risk factors utilizing exposure data accumulated prospectively over the past 39 years. Findings include significantly lower SN neuron densities in PD cases compared to controls without PD. Further, duration of PD is highly correlated with SN neuron density. Brains with incidental Lewy bodies have intermediate mean densities. These relationships are strongest for the ventrolateral quadrant. Mid-life risk factors found preliminarily to predict low SN neuron density at death include high total kilocalorie intake, dietary iron and manganese, non-smoking of cigarettes, work on a sugar or pineapple plantation, high body mass index, increased time spent in edentary activity, and (in late life) slowed reaction time. Contrary to expectation, an association of advanced age with deceased SN neuron density was not found. To assess the influence of age with qreater certainty a new Aim is proposed: measurement of SN neuron densities in study subjects dying at a younger age, using archived materials from 160 cohort autopsies done prior to 1991. A second important and unexpected finding is of remarkably low SN neuron densities in the absence of Lewy bodies, but in association with parkinsonian signs, in a subset of the decedents. A second new Aim is proposed to extend investigations of this subset by applying a-synuclein immunohistochemistry to areas of brainstem, limbic regions, cortex, and olfactory bulb. These histopathologic studies will help to determine if the subset of decedents with isolated SN neuron loss represents a prodromal phase of PD, or a pathogenesis not associated with a-synucleinopathy. Continuation will allow accrual of SN neuron density measurements for 800 total autopsies, and 440 striatal dopamine assays. The greater numbers will dramatically enhance statistical power for substantiating risk factors preliminarily identified or suspected. This will also provide opportunity to examine the influence of a wider age range, as well as additional occupational, dietary, medical, constitutional, and environmental exposures on SN neuron density and striatal dopamine levels.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2008	PACIFIC HEALTH RESEARCH & EDUCATION INSTITUTE	459 PATTERSON ROAD E WING 151	HONOLULU	HI	96819	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	4/15/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $56,496 )
2010	2010	PACIFIC HEALTH RESEARCH EDUCATION INSTITUTE	459 PATTERSON ROAD E WING 151	HONOLULU	HI	96819	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	10	9/9/2010	SUPPLEMENT FOR EXPANSION	$56,496
2010	2008	PACIFIC HEALTH RESEARCH EDUCATION INSTITUTE	459 PATTERSON ROAD E WING 151	HONOLULU	HI	96819	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	9/9/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,843
2010	2008	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	5/13/2010	NON-COMPETING CONTINUATION	$0
2010	2008	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	9/8/2010	NON-COMPETING CONTINUATION	-$17,843
														Subtotal = $56,496

Issue Date FY: 2009 ( Subtotal = $0 )
2009	2008	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	12/3/2008	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $746,350 )
2008	2008	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	4/14/2008	NON-COMPETING CONTINUATION	$746,350
														Subtotal = $746,350

Issue Date FY: 2007 ( Subtotal = $774,826 )
2007	2007	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	6/7/2007	NON-COMPETING CONTINUATION	$774,826
														Subtotal = $774,826

Issue Date FY: 2006 ( Subtotal = $790,804 )
2006	2006	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	5/19/2006	NON-COMPETING CONTINUATION	$790,804
														Subtotal = $790,804

Issue Date FY: 2005 ( Subtotal = $790,992 )
2005	2005	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	5/31/2005	NON-COMPETING CONTINUATION	$790,992
														Subtotal = $790,992

Issue Date FY: 2004 ( Subtotal = $753,822 )
2004	2004	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	9/9/2004	COMPETING CONTINUATION	$753,822
														Subtotal = $753,822

Issue Date FY: 2003 ( Subtotal = $452,620 )
2003	2003	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/29/2003	NON-COMPETING CONTINUATION	$452,620
														Subtotal = $452,620

Issue Date FY: 2002 ( Subtotal = $452,417 )
2002	2002	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Biological Basis Research in the Neurosciences	000	3	7/29/2002	NON-COMPETING CONTINUATION	$452,417
														Subtotal = $452,417

Issue Date FY: 2001 ( Subtotal = $486,009 )
2001	2001	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	6/12/2001	SUPPLEMENT FOR EXPANSION	$50,000
2001	2001	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/27/2001	NON-COMPETING CONTINUATION	$425,659
2001	2001	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	4/2/2001	SUPPLEMENT FOR EXPANSION	$10,350
														Subtotal = $486,009

Issue Date FY: 2000 ( Subtotal = $467,091 )
2000	2000	PACIFIC HEALTH RESEARCH INSTITUTE	846 SOUTH HOTEL STREET	HONOLULU	HI	96813	HONOLULU	USA	Biological Basis Research in the Neurosciences	000	1	9/13/2000	NEW	$467,091
														Subtotal = $467,091

Grand Total All Awards = $5,771,427

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RISK FACTORS FOR PATHOLOGIC MARKERS OF PARKINSON DISEASE

Award Number: R01NS041265

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2000

PERIOD OF PERFORMANCE END DATE: 05/31/2012

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