Oral Sessions: O5-04: Diagnosis and Prognosis: Diagnostic Implications of Vascular FactorsP836

which volumetric measures of the hippocampus, grey matter, white matter

and white matter hyperintensity volumes. Results: Our results indicate

widespread microstructural deterioration in the NAWM in MCI patients

with CSVD, whileMCI patients without CSVD show FA decrease restricted

to the temporal lobe, the perforant path. Within the full cohort of MCI

patients, microstructural integrity within the NAWM of DMN fiber

tracts was found to be affected mainly by the presence of CSVD. Within

specifically the cingulum along the hippocampal cortex we found a re-

lationship between microstructural integrity and ipsilateral hippocampal

volume as well as the extent of macrostructural manifestations of CSVD.

Conclusions:We found evidence of vascular disease relatedmicrostructural

damage in important fiber tracts that subserve the DMN in patients with

MCI. These findings indicate that CSVD plays an important role in

NAWM structural integrity in MCI patients.

O5-04-03 CAN NEAR INFRARED SPECTROSCOPY BE USED

FOR EARLY DETECTION AND DIAGNOSIS OF

BRAIN MICROVASCULAR DISEASE?

Aron Troen, Hebrew University of Jerusalem, Rehovot, Israel. Contact

e-mail: troen@agri.huji.ac.il

Background: The contribution of commonly occurring microvascular

changes to dementia have received far less attention than neurodegenerative

changes, despite their theoretical significance in the early and potentially

preventable stages of cognitive decline. We and others have found a loss

of capillaries to correlate with cognitive decrements and precede neurode-

generation in animals. Methods: To understand the functional impact of

such microvascular loss, w e developed an innovative non-invasive near in-

frared spectroscopy (NIRS) instrument, which is particularly sensitive to the

microvasculature and which allows us to measure absolute brain hemoglo-

bin concentration (reflecting microvascular volume) and oxygen saturation

at rest and in response to physiologic challenges in rat. We used this method

evaluate cerebral blood volume and vascular reactivity in several animal

models as a function of age, hypertension and dietary vascular risk (hyper-

homocysteinemia). Results: Our findings document reproducible decre-

ments in absolute hemoglobin concentrations between control animals

and experimental conditions, indicating substantial structural microvascular

loss, even when the relative vascular reactivity did not differ between groups

(i.e. percent change from resting conditions). Moreover, in our model of di-

etary vascular-risk, we were able to mitigate and reverse the decrease in ab-

solute hemoglobin concentration, indicating a significant degree of vascular

plasticity. Finally, our longitudinal findings in rats of decreasing brain he-

moglobin concentrations with age, was consistent with our preliminary

cross-sectional study comparing young adult and old humans.Conclusions:

Our findings indicate that non-invasive absolute NIRS may be useful as

a biomarker for the early detection and monitoring of brain microvascular

disease in humans.

O5-04-04 ADIPOSITY INDICATORS AND BRAIN

STRUCTURE

Nikolaos Scarmeas1, Yian Gu2, Yaakov Stern3, Charles S. Decarli4,

Jennifer Manly1, Richard Mayeux2, Adam Brickman2, 1Columbia

University Medical Center, New York, New York, United States; 2Columbia

University, New York, New York, United States; 3Columbia University,

Department of Neurology, New York, New York, United States; 4University

of California-Davis, Sacramento, California, United States. Contact e-mail:

ns257@columbia.edu

Background: Previous studies have reported associations between adipos-

ity indicators, such as bodymass index (BMI) or waist-hip ratio (WHR), and

cognition or risk of dementia in the elderly, but little is known whether BMI

and WHR are also associated with brain imaging biomarkers. We aimed to

examine the relationships between BMI or WHR and brain structure in cog-

nitively healthy elderly.Methods: High-resolution structural magnetic res-

onance imaging (MRI) was collected on 717 non-demented community

elderly (aged �65) participants of the multi-ethnic Washington Heights-In-

wood Columbia Aging Project imaging sub-study with available BMI (kg/m

2) and WHR assessments administered at the same visit. Total brain volume

(TBV) was adjusted for total cranial volume. Total white matter hyperinten-

sity volume (WMHV) was log-transformed to yield a normal distribution.

Brain infarction lesions that were 3 mm or larger qualified for consideration

as subclinical brain infarcts (SBI). We used linear regression to examine

whether BMI andWHR are associated with TBVorWMHV.We used logis-

tic regression to examine the association of BMI (or WHR) with SBI.

Models were adjusted for age, gender, ethnicity, and cognition. Interaction

terms were added to the model to examine whether the association between

adiposity markers and MRI markers are modified by these covariates.

Results: Subjects with higher WHR had greater TBV (b¼0.04; p¼0.007),

and marginally positively related to WMHV (b¼0.53; p¼0.07). Even

when simultaneously including BMI in the model there was still a positive

association between WHR and TBV (b¼0.04; p¼0.006), and a marginally

significant positive association between WHR and WMHV (b¼0.54;

p¼0.08). The associations of WHR with TBVand WMHV were both mod-

ified by ethnicity, with significant WHR-TBV in Blacks and WHR-WMHV

association in Hispanics. WHR was not associated with SBI (OR¼1.76;

95%CI: 0.39-7.95). BMI was not associated with TBV (b¼-.00004;

p¼0.13), WMHV (b¼-0.006; p¼0.30) or SBI (OR¼0.98; 95% CI: 0.95-

1.01). Conclusions: Atrophy and WMH may reflect different underlying

neurobiological changes in aging brain (i.e. neurodegeneration and vascular

damage, respectively). We found that elderly subjects with higherWHR had

less atrophy and moreWMH over and above BMI values. Adiposity indices

may bear different, even opposing relations with underlying neurobiological

processes.

O5-04-05 IS THERE A LINK BETWEEN NOVEL RETINAL

AND CEREBRAL MARKERS OF

MICROVASCULAR PATHOLOGY?

MohammadKamran Ikram1, Yi TingOng2, SaimaHilal3, Carol Cheung2,

Monica Saini1, Ainur Anuar2, Merwyn Chew2, Tien Yin Wong2,

Christopher Chen1, Narayanaswamy Venketasubramanian1, 1National

University of Singapore, Singapore, Singapore; 2Singapore Eye Research

Institute, Singapore, Singapore; 3National University Health System,

Singapore, Singapore. Contact e-mail: kamran_ikram@nuhs.edu.sg

Background:Qualitative retinal vascular changes such as retinopathy signs

have been linked to cognitive impairment and subclinical neuroimaging

markers such as silent infarcts and white matter lesions. Recent advances

in retinal imaging have enabled us to assess novel quatitative retinal vascular

parameters, whilst concomitantly advances in neuroimaging have revealed

cerebral microbleeds (CMB) to be a novel marker for microvascular pathol-

ogy in the brain. We examine the association between novel retinal imaging

markers and the presence of cerebral microbleeds (CMB) on magnetic res-

onance imaging (MRI). Methods: A total of 300 participants (age�60

years) subjects participated in the Chinese component of the on-going

Epidemiology of Dementia in Singapore (EDIS) Study. All participants

Oral Sessions: O5-05: Public Health and Psychosocial Focus: Epidemiology IV—Protection and Risk P837

underwent an extensive examination, including retinal photography and 3T

cranial MRI. Retinal vascular parameters (caliber, tortuosity, fractal dimen-

sion) were assessed from fundus images using a semi-automated computer-

based program. The presence and number of CMBs were assessed using the

Brain Observer Microbleed Scale (BOMBS) on susceptibility weighted im-

aging sequences. Poisson regression models were constructed, adjusting for

age, gender, smoking status, body mass index, mean arterial blood pressure,

fasting blood glucose, blood cholesterol, and additionally for total white

matter volume, total brain volume, presence of stroke and intracranial steno-

sis. Results: A total of 239 participants who had gradable fundus photo-

graphs and MRI scans were included in this analysis. CMB were present

in 75 participants, of whom 48 had a single CMB and another 27 subjects

had�2 CMBs. In the multivariate adjusted models, smaller arteriolar fractal

dimensions (multi-variable adjusted rate ratio [RR] per standard deviation

[SD] decrease: 1.42; 95% confidence interval: 1.17-1.74), increased arteri-

olar tortuosity (RR per SD increase: 1.26; 95% CI: 1.04-1.53), narrower ret-

inal arteriolar caliber (RR per SD decrease: 1.55; 95% CI: 1.05-2.33) and

wider venular caliber (RR per SD increase: 1.55; 95%CI: 1.05-2.33) were

associated with increasing numbers of CMB on MRI. Conclusions: In

this study we found that a sparser and a more tortuous microvascular net-

work in the retina is related to presence of CMB on MRI, suggesting com-

mon pathophysiological mechanisms may underlie both retinal and cerebral

microvascular pathology.

O5-04-06 LONGITUDINAL CHANGES IN WHITE MATTER

DISEASE AND COGNITION IN SUBCORTICAL

VASCULAR MILD COGNITIVE IMPAIRMENT

Hee-Jin Kim1, Young Noh1, Hanna Cho1, Cindy Yoon2, Byoung Seok Ye1,

Geon Ha Kim1, Seun Jeon3, Jong Min Lee3, Jung-Hyun Kim1,

Yearn Seong Choe4, Kyung-Han Lee1, Changsoo Kim5, Jae Hong Lee6,

Duk L. Na1, SangWon Seo7, 1Samsung Medical Center, Seoul, Seoul, South

Korea; 2Department of Neurology, Samsung Medical Center,

Sungkyunkwan University School of Medicine, Seoul, South Korea;3Hanyang University, Seoul, South Korea; 4Sungkyunkwan University

School of Medicine, Samsung Medical Center, Seoul, South Korea; 5Yonsei

University College of Medicine, Seoul, South Korea; 6University of Ulsan

College of Medicine, Asan Medical Center, Seoul, South Korea; 7Samsung

Medical Center, Sungkyunkwan University School of Medicine, Seoul, South

Korea. Contact e-mail: evekhj@gmail.com

Background: Increasing evidences suggest that a strong association exists

between cerebrovascular disease (CVD) and Alzheimer’s disease (AD).

However, few studies have evaluated the relationship between CVD and

AD pathologies in living human subjects, or their effects on cognition.

We investigated a longitudinal data in subcortical vascular mild cognitive

impairment (svMCI), a prodromal stage of subcortical vascular dementia.

We aimed (1) to assess the significance of co-existing AD pathology which

was measured by 11 C-Pittsburgh Compound-B (PiB)-PET at baseline, as

a predictor of changes in CVD, measured as white matter hyperintensities

(WMH) and lacunes, (2) to evaluate the relationship between baseline am-

yloid burden and CVD and changes in cognitive performance, (3) to deter-

mine whether longitudinal changes in CVD are associated with changes in

cognition. Methods: We prospectively recruited 67 svMCI patients who

were annually followed up with MRI and neuropsychological tests for

3.85 years. 32.8% of svMCI patients were determined to be PiB(+) which

was defined as PiB retention ratio greater than 1.5. We performed

mixed-effect-models after controlling possible confounders. Results: PiB-

positivity in svMCI patients was not associated with increase in WMH vol-

ume or number of lacune. However, as compared to PiB(-) patients, PiB(+)

svMCI patients had greater decline in Boston naming test (p<0.001), Seoul

verbal learning test (p¼0.002), Controlled oral word association

test(p<0.001), and clinical dementia rating scale sum of box (CDR-SOB)

(p<0.001). Baseline WMH volume and number of lacune were not associ-

ated with rate of cognitive decline in any domain. There was no interactive

effect of baseline PiB retention ratio and baseline CVD burden on cognitive

decline. Greater increase in lacunewas associated with rapid decline in digit

span backward (p¼0.030), Stroop color reading (p<0.001), and CDR-SOB

(p¼0.045). Greater increase in WMH was associated with rapid decline in

Stroop color reading (p¼0.012) and CDR-SOB (p¼0.047). Conclusions:

Our findings suggest that concomitant AD pathology is a strong predictor

of subsequent cognitive decline in svMCI patients, but does not play

a role in the progression of CVD burden. Progression of CVD results in

rapid decline in frontal function, independent of amyloid burden. Thus am-

yloid and vascular pathway leading to cognitive decline, are probably

independent.

ORAL SESSIONS: O5-05:

PUBLIC HEALTH AND PSYCHOSOCIAL FOCUS:

EPIDEMIOLOGY IV—PROTECTION AND RISK

O5-05-01 MIDLIFE PROBLEM DRINKING AND RISK OF

COGNITIVE DECLINE AND DEMENTIA: AN 18-

YEAR PROSPECTIVE COHORT STUDY

Elzbieta Kuzma1, David Llewellyn1, Maya Soni1, Kenneth Langa2,

Robert Wallace3, Iain Lang1, 1University of Exeter Medical School, Exeter,

United Kingdom; 2University of Michigan, Ann Arbor, Michigan, United

States; 3University of Iowa, Iowa City, Iowa, United States. Contact e-mail:

elzbieta.kuzma@pcmd.ac.uk

Background: In the US, lifetime prevalence of problem drinking is increas-

ing. Little is known about the long-term consequences of midlife problem

drinking on risk of cognitive decline and incident dementia in later life.

Methods: We used data on 6686 participants aged 51 through 61 in the

Health and Retirement Study (HRS), a biennial, prospective, nationally rep-

resentative study of older US adults. Participants were followed from 1992

baseline until 2010 or until death or drop-out (mean years of follow-up ¼15.7 years, standard deviation 3.8). Problem drinking was identified using

the three-item modified CAGE (i.e. omitting the question on “cutting

down”), a widely used screening instrument, with problem drinking defined

as a score � 1. O outcomes were cognitive decline on the 35-item modified

Telephone Interview for Cognitive Status (mTICS), and severe cognitive

impairment indicative of incident all-cause dementia (mTICS score �8).

Linear and logistic regression models were adjusted for age, gender, race,

education, current smoking status, depressive symptoms, history of diabetes

or hypertension, years of follow-up, and baseline cognitive functioning.

Results: Problem drinkingwas reported by 16.7% of participants at baseline

and was more common in men, younger participants, thosewith lower levels

of education, and smokers. In fully adjusted models, problem drinking was

significantly associated with cognitive decline (B ¼ -0.42, 95% confidence

interval [CI] 0.14 to 0.71), and a doubling of the odds of incident dementia

(odds ratio ¼ 2.03, 95% CI 1.10 to 3.68). Conclusions: Midlife problem

drinking was associated with a substantially increased risk of cognitive de-

cline and incident dementia in later life. The CAGE instrument, which is

quick and straightforward to administer, may offer clinicians a practical

way to identify and intervene in individuals at elevated risk of future adverse

cognitive outcomes as a result of problem drinking.

O5-05-02 RISK AND PROTECTIVE FACTORS FOR

DEMENTIA IN PEOPLE 85 AND OLDER

Karin Wallin1, Gustaf Bostr€om2, Miia Kivipelto1, Yngve Gustafson3,1Karolinska Institutet, Stockholm, Sweden; 2Ume�a University, Ume�a,

Sweden; 3Ume�a Universitet, Ume�a, Sweden. Contact e-mail: karin.wallin@

ki.se

Background: The size of the older population is increasing worldwide, and

those 80 years and older comprise the fastest growing group. There are sev-

eral established risk factors for Alzheimer’s disease (AD), cognitive impair-

ment (CI) and dementia from mid to late life. However, knowledge about

such factors in people �85 years is limited. The present study aims to iden-

tify independent factors associated with risk of dementia incurred over

a 5-year period. Methods: The Ume�a85+/GERDA study, a population-

based cohort study of those aged 85, 90 and 95+ years, was used. Baseline

material was collected from 2000 through 2002. After 5 years of follow-up,

it was possible to evaluate 212 participants. Of these, 71 developed demen-

tia. Results: Presence of depression at baseline was associated with higher