Poster Presentations P2 S369

P2-174 ENHANCED RISK OF MILD

COGNITIVE IMPAIRMENTAND ITS

PROGRESSION TO DEMENTIA AMONG

APOE e4 CARRIERS

Weili Xu1, Weili Xu2, Yaogang Wang3, Barbara Caracciolo2, Hui-

Xin Wang2, Bengt Winblad2, Laura Fratiglioni2, 1Aging Research Center,

Aging Research Center, Sweden; 2Karolinska Institutet, Stockholm, Sweden;3Tianjin medical University, Tianjin, China.

Background: The contribution of APOE 34 to mild cognitive impairment

(MCI) and its progression to dementia remains challenging. We sought to

examine whether APOE 34 is associated with the development of MCI,

and accelerate progression from MCI to dementia. Methods: In the Kung-

sholmen Project, 756 cognitively intact participants and 212 people with

MCI (88 amnestic MCI [aMCI] and 124 other cognitive impairment no de-

mentia [oCIND]) aged ¼ 75 were identified at baseline. The two cohorts

were followed for 9 years to detect incident MCI and dementia cases follow-

ing international criteria. APOE genotypes were assessed using standard

procedure. Data were analyzed using Cox models with adjustment for po-

tential confounders.Results:During the follow-up period, in the cognitively

intact cohort, 165 people developed MCI (40 aMCI and 125 oCIND), and

176 developed dementia (126 Alzheimer’s disease); in the MCI cohort,

118 persons progressed to dementia. Compared with APOE 3333 genotype,

the hazard ratios (HRs) (95% confidence interval) of 3234/3334 genotype

was 1.65 (1.15-2.38) for MCI, 2.24 (1.10-4.57) for aMCI, and 1.78 (1.15-

2.75) for oCIND, while the ?4?4 was related to dementia with HR of 4.35

(1.97-9.63) in the cognitively intact cohort. In the MCI cohort, the 3434 ge-

notype led to a multi-adjusted HR of 2.89 (1.12-7.48) for conversion to de-

mentia, and accelerated the progression from MCI to dementia by 3.36

years. Conclusions: The APOE e4 heterozygotes are associated with an in-

creased risk of MCI, aMCI and oCIND. The e4 homozygote accelerates the

progression from MCI to dementia, and anticipate dementia occurrence by

more than 3 years in people with MCI.

P2-175 MIDLIFE AND ELDERLY BIOLOGIC

FUNCTIONS AND DEMENTIA:

RADIATION EFFECTS RESEARCH

FOUNDATION ADULT

HEALTH STUDY

Michiko Yamada1, Fumiyoshi Kasagi1, Yasuyo Mimori2,

Takafumi Miyachi3, Tomohiko Ohshita3, Hideo Sasaki4, 1Radiation Effects

Research Foundation, Hiroshima, Japan; 2Hiroshima International

University, Higashihiroshima, Japan; 3Hiroshima University Graduate

School of Biomedical Sciences, Hiroshima, Japan; 4Hiroshima Atomic

Bomb Casualty Council Health Promotion Center, Hiroshima, Japan.

Background: Biologic functions such as grip strength (grip) and reaction

time (RT) are not only associated with clinical and subclinical age-related

health status in a cross-sectional study but also are predictors of future health

events. However, only a few longitudinal studies have been conducted on

association between midlife and elderly biologic functions and dementia.

We investigated whether midlife grip and RT and/or elderly grip are associ-

ated with dementia risk in the population-based cohort of the Radiation Ef-

fects Research Foundation’s Adult Health Study (AHS). Methods: AHS

biennial health examinations have been conducted since 1958. Grip and

RT were measured in 1,785 participants born between 1917 and 1932, at

clinical examinations during the period 1970 - 1972. By September 1992,

487 subjects had died or dropped out of the follow-up. The remaining

1,298 subjects were assessed in terms of cognitive function and presence

of dementia biennially between 1992 and 2007. Elderly grip was measured

at baseline examination for assessment of dementia. Relative risk (RR) of

dementia incidence associated with grip and RT was estimated by Poisson

regression analysis after adjustment for radiation dose. Results:Midlife re-

action time was found to be an independent risk factor of dementia inci-

dence. Effects of education and midlife grip were no longer significant

after adjustment was made for midlife RT. Elderly grip also was found to

predict dementia occurrence. Conclusions: In this prospective study of

Japanese, biologic aging, marked by slower midlife reaction time and

weaker elderly grip strength, was found to be a predictor of dementia

incidence.

P2-176 NON-HOMOGENEOUS MARKOV

PROCESS MODELS WITH

INFORMATIVE OBSERVATION

TIMES, WITH AN APPLICATION TO

ALZHEIMER’S DISEASE

Baojing Chen1, Xiao-Hua Andrew Zhou2, 1University of Nebraska,

Omaha, Nebraska, United States; 2University of Washington, Seattle,

Washington, United States.

Background: Identifying risk factors for transition rates among normal

cognition, mild cognitive impairment (MCI), dementia and death is very im-

portant. It is known that transition rates among these states vary over time.

While Markov process models are often used to describe these disease pro-

gressions, the literature mainly focuses on time homogeneous processes,

and limited tools are available for dealing with temporal non-homogeneity.

Furthermore, the timing of observations may vary among patients, and the

time interval between visits can affect transition probabilities. Methods:

We developed new statistical methods to deal with non-homogeneous Mar-

kov processes through time scale transformation when observation times are

pre-planned but with some observations missing. We also conducted a sim-

ulation study to compare the relative performance of the new method with

the most commonly used complete case analysis which removes any sub-

jects with missing visits. We then applied the method to the Uniform Data

Set (UDS) at the National Alzheimer’s Coordinating Center (NACC). The

UDS involves standardized longitudinal data collection at 29 NIA funded

Alzheimer’s Disease Centers (ADCs) across the United States since 2005.

Our analytic data set included 7,932 subjects with or without cognitive im-

pairment. Follow-up visits for subjects were scheduled at approximately

one-year intervals, with up to five clinical visits. Risk factors included:

age at first clinic visit, sex, education (years), family history of dementia

(yes/no), congestive heart failure (CHF-yes/no), diabetes (yes/no), hyper-

tension (yes/no), Geriatric Depression Score (GDS), and MMSE score.

Results: The simulation study shows that the proposed method gives satis-

factory results with small finite sample biases and good coverage probabil-

ities. However, the complete case method yields large biases and poor

coverage probabilities. Using the new method, we found that family history

of dementia and age were significant factors in the transitions from normal

cognition to MCI. In the transitions from MCI to dementia, sex, GDS and

age were significant factors. In the transition from dementia to death, sex,

CVCHF, GDS, education and age were significant factors. Conclusions:

Our newly proposed method for modeling disease progression is very ap-

pealing in that it can deal with all kinds of missing data mechanisms and

non-homogeneous transition intensities. The application of our new method

to the NACC UDS revealed some risk factors associated with disease tran-

sition probabilities.

P2-177 CORRELATION BETWEEN ATRIAL

FIBRILLATION, STROKE AND

DEMENTIA

Gratiela Baidac1, Alice Petrescu1, Alexandru Sterea1, Luiza Spiru1, 1Ana

Aslan International Academy of Aging, Bucharest, Romania.

Background: Atrial fibrillation (AF) is a frequent disorder in the elderly

and a known risk factor for cerebrovascular stroke. Our study aims to inves-

tigate the association between AF, stroke and different types of dementia,

and more precisely if AF may contribute directly to the development of cog-

nitive dysfunction.Methods:The studywas performed on 181 patients aged

over 70 (124 female), with all types of dementia, referred to the Geriatric

Clinic of the Elias Hospital (Bucharest). The diagnostic of dementia was

based on Standardized Geriatric Evaluation; AF was ECG-documented;

the stroke was documented by both neurological examination and brain im-

aging (CTor MRI).Results: In the study group, n¼ 94 (51.93%) hadMixD

(mixed dementia), n ¼ 32 (17.67%) had VaD (vascular dementia) and n ¼55 (30.40%) had AD (Alzheimer’s dementia). AF was identified in n ¼ 51