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Poster Presentations P3P388
FOME scores when compared to those with WMH ratings below the 50th
percentile. Conclusions: A history of CABG is an apparent risk factor for
developing aMCI and dementia as well as for having higher WMH ratings.
Those with CABG who had high WMH ratings had greater medial temporal
atrophy, suggesting that there are related mechanisms for developing WMH
and neurodegenerative disease among these subjects.
P3-149 CONVERSION OF MILD COGNITIVE
IMPAIRMENT (MCI) TO ALZHEIMER DISEASE
(AD): RISK FACTORS
Spiru Luiza, Turcu Ileana, Ana Aslan International Academy of Anti-Aging,Bucharest, Romania. Contact e-mail: [email protected]
Background: The identification of inner and environmental risk factors
influencing the progression rate from predementia conditions to Alzheimer’s
disease is a challenge. They may vary depending on geographical, social and
cultural determinants. Methods: Sixty MCI subjects between 60-75 years,
77% women/23% men, 37% university graduated and 90% from urban
area were studied at ‘‘Elias’’ University Hospital, Bucharest in a three years
follow up, as the Romanian contribution to the DESCRIPA Study developed
by EADC. Their MCI to AD conversion rate was corroborated with their co-
morbidity incidences and certain of their social and lifestyle items, character-
istic for rural vs, urban areas. Results: The MCI to AD conversion rate was of
29.9%. Comorbidity items (hypertension, angina pectoris, dyslipidemia, di-
abetes type II, osteoporosis, transient ischemic attack, hypothyroidism, ca-
rotid artery stenosis and depression) were prevalent in women. In our
patients sample hypertension and dyslipidemia should be the main conver-
sion risk factors. A close correlation was found between co-morbidity items,
education degree and lifestyle in rural or urban area. Conclusions: Compar-
ative study of the results obtained on the Romanian patients group with those
reported by other international partners in the DESCRIPA Consortium could
be able to contribute to the validation of the international risk factors distri-
bution patterns for Alzheimer’s disease onset and development.
P3-150 HISTONE ACETYLATION ENHANCES
NEUROTROPHIN EXPRESSION AND SYNAPTIC
PLASTICITY IN AGING BRAIN
Cui-Wei XIE, Xiao Feng Yin, Yan Zeng, Joseph B. Watson, UCLA, Los
Angeles, CA, USA. Contact e-mail: [email protected]
Background: Recent studies have shown that chromatin modification via
histone acetylation plays an important role in synaptic plasticity and memory
storage. The cellular basis and therapeutic potentials of this epigenetic regu-
latory mechanism remain to be further explored. We have examined whether
regulation of histone acetylation affects changes in hippocampal synaptic
plasticity associated with aging, one of the best known risk factors for Alz-
heimer’s disease. Methods: Hippocampal long-term potentiation (LTP) was
determined in brain slices derived from young (1-2 months old) and old (12-
14 months old) Sprague-Dowley rats. Western blot analysis was used to mea-
sure age-dependent and drug-induced changes in the expression of several
proteins crucial for synaptic plasticity and memory function. Results: A
high frequency stimulation (HFS) to the Schaffer collateral-CA1 pathway
induced long-lasting increases in evoked synaptic responses in young but
not old slices (153+13% vs. 106+11% at 60 min post-HFS, p<0.01). Pre-
incubation of slices for 3 hr with trichostatin (TSA), a histone deacetylase
(HDAC) inhibitor, selectively enhanced LTP in old slices (140+15%,
P<0.01) but caused only insignificant changes in LTP of young slices.
Western blot analyses demonstrated that impairment of hippocampal
LTP in old animals was associated with significant reductions in histone
3 (H3) acetylation and expression levels of brain-derived neurotrophic fac-
tor (BDNF) and trkB receptors in hippocampal tissue. Treatment with
TSA induced a robust increase in H3 acetylation in old slices, which
led to significant upregulation of BDNF and trkB levels. The same treat-
ment in young slices, however, produced minimum effect. Our previous
studies showed that BDNF rescued amyloid-b induced synaptic dysfunc-
tion by enhancing phosphorylation of Ca2+ and calmodulin-dependent pro-
tein kinase II (CaMKII) and GluR1 subtype of glutamate receptors.
Consistent with these findings, upregulation of the BDNF-trkB system
in TSA-treated old slices resulted in significant increases in the phosphor-
ylation of CaMKII and GluR1, which could well explain the rescue of
LTP in these slices. Conclusions: Our findings suggest that age-depen-
dent decline in histone acetylation leads to down-regulation of the
BDNF-trkB system, contributing to aging-related impairment of hippo-
campal synaptic plasticity. Therapeutic strategies that enhance histone
acetylation therefore may prove beneficial for aging and Alzheimer’s dis-
ease-associated synaptic and memory deficits.
P3-151 MODELING RESERVE WITH CHANGE OVER TIME
Laura S. Hemmy1, Michael A. Kuskowski2, Karen S. SantaCruz1,
Kelvin O. Lim1, 1University of Minnesota, Minneapolis, MN, USA;2GRECC, VAMC, Minneapolis, MN, USA. Contact e-mail: hemmy001@
umn.edu
Background: Most investigations of predictors of resiliency to cognitive im-
pairment in late life focus on discrete outcome status (i.e. dementia vs. no de-
mentia). However, hypothesized reserve effects can also be modeled as
differential trajectories of change over time. The extensive longitudinal
data in the Nun Study are ideal for exploring this analysis strategy. Hypoth-
eses of the cognitive reserve theory were investigated by testing for a relation
between educational attainment and rate of cognitive decline. Methods: The
Nun Study is a longitudinal study of aging in 678 participants aged 75þ years,
recruited from a congregation of 1027 sisters living in the United States. Anal-
yses using mixed effect regression models evaluated rate of change on global
and memory-specific cognitive outcomes (MMSE and CERAD word list re-
call), and the effect of education on intercept and slope (including age as a co-
variate). The sample was first limited to all study participants with two or
more evaluation time points (n¼442), and then to those with available Braak
staging and ApoE4 status. Results: Education was significantly related to ini-
tial intercepts (MMSE: 1.701, SE¼.404, p¼.000; Word Recall: .716,
SE¼.155, p¼.000), but not the slopes of both cognitive outcomes. Two ad-
ditional sets of models were run with participants split into 1) Braak stages
0-2 vs. 3-6, and 2) ApoE4 vs no 4. Education maintained a significant effect
on the intercept in each model, and demonstrated an effect on slope for those
in Braak 0-2 (MMSE: .230, SE¼.093, p¼.015), Braak 3-6 (Word Recall:
-.074, SE¼.028, p¼.008), those with ApoE4 (Word List: -.107, SE¼.048,
p¼.030), and those without ApoE4 (MMSE: .194, SE¼.075, p¼.01). Con-
clusions: Education was consistently related to initial cognitive status. How-
ever, its relationship to rate of cognitive decline was inconsistent. These
results are discussed within the framework of cognitive reserve.
P3-152 THE ASSOCIATION BETWEEN VASCULAR RISK
FACTORS AND KOREAN ALZHEIMER’S DISEASE
PATIENTS
Hee Jin Kang, Yong Shin Yoon, Jung Eun Kim, Seunga Ko,
Ji Young Yeom, Ki Duk Park, Kyong Gyu Choi, Jee H. Jeong, Department
of Neurology, Center for Cognitive & Neurogenerative Disorders, Ewha
Womans University School of Medicine, Mokdong, Yangcheon-gu, Republicof Korea. Contact e-mail: [email protected]
Background: With the epidemiologic evidence supporting the vascular dis-
ease as an important risk factor for AD, we aimed to evaluate the influence of
the major vascular risk factors to the prevalence in possible and probable Ko-
rean AD patients. Methods: Of the total 260 possible and probable AD pa-
tients, 186 patients fulfilling inclusion criteria were gathered from the
Dementia Cohort from Cognitive and Language Disorder clinic, Ewha
Womans University from 2003 through 2008. Inclusion criteria at the time
of diagnosis were 1) probable or/possible AD 2) Brain MRI including T2,
Flair and T1 images 3) homocysteine, Vit B12, Folic acid 4) Fasting sugar
5) Blood pressure 6) HDL-Chol, LDL-Chol, TG, Total Chol 7) EKG and
8) obtained medical history of vascular risk factor (Hypertension, DM, hy-
percholesterolemia, heart disease, stroke) and conventional AD risk factors.
Cognitive functions were measured as D-score of Seoul Neuropsychological
Screening Battery (SNSB), functional measure as S-IADL. Ischemic subcor-
tical hypertintensities with Fazekas grade in deep white matter (DWM), peri-
ventricular white matter (PVWM) and deep subcortical gray matter (DSGM,
including caudate, putamen and thalamus) with FLAIR and T2W images.
Poster Presentations P3 P389
Results: Each mean age 6 SD of AD and non-AD control was 72.3268.66
and 71.036 7.75. Sex ratio of female to male was about 2: 1. Among the vas-
cular risk factors, DM and PVH was statistically significant factor in AD pa-
tients than non-AD patients. The severity of white matter changes was not
associated with severity of dementia in AD. Conclusions: DM and PVH
had a higher prevalence in AD patients than non-AD patients. Thus, control
of DM may reduce the risk of AD development. PVH might have several
causative factors, and may have some clinical significance of AD, the change
itself does not contribute to the progression of AD.
P3-153 SURGERY USING GENERAL ANESTHESIA AND
RISK OF DEMENTIA IN THE AGING,
DEMOGRAPHICS AND MEMORY STUDY
Brenda L. Plassman1, Kenneth M. Langa2, Emily V. A. Finlayson2,
Mary A. M. Rogers2, 1Duke University Medical Center, Durham, NC, USA;2University of Michigan, Ann Arbor, MI, USA. Contact e-mail: brenda.
Background: Short-term postoperative cognitive dysfunction is common
among the elderly. However, to date there has been minimal evidence to sup-
port continued postoperative cognitive decline beyond 6 months. We exam-
ined the association between surgery conducted under general anesthesia and
risk of dementia in a nationally representative sample in the United States.
Methods: We used data from the Aging Demographics and Memory Study
(ADAMS), a population-based study of dementia that used a single standard-
ized diagnostic protocol and included subjects from all regions of the country.
The ADAMS sample of 856 individuals aged 70 years or older was drawn
from participants in the ongoing Health and Retirement Study (HRS). All par-
ticipants received an extensive in-home clinical and neuropsychological as-
sessment to determine a diagnosis of normal cognition; cognitive
impairment, not demented; or dementia. We obtained the full set of Medicare
administrative records from 1991-2005 to determine details of each partici-
pant’s surgical history prior to the outcome date, defined as the estimated
age of onset for the demented and the ADAMS assessment date for non-de-
mented individuals. We used proportional hazards models to examine the as-
sociation between exposure to general anesthesia and the risk of dementia vs.
normal cognition. Results: We found that surgery with general anesthesia
was associated with increased risk of dementia (Hazard Ratio (HR) ¼ 2.90;
95% CI ¼ 1.70-4.93), independent of the number of hospitalizations prior
to the outcome date. This association was evident for non-cardiovascular sur-
geries (HR¼3.01; 95% CI¼1.55-5.82) but less so for cardiovascular surgeries
(HR¼2.17; 95% CI¼0.94-5.04). When persons with less than 2 years of
Medicare claims and those with questionable cognition at baseline were ex-
cluded, the association between general anesthesia and dementia remained
(HR¼2.69; 95% CI¼1.51-4.80). Persons with dementia had 27 hospitaliza-
tions per 100 person-years compared to 15 hospitalizations/100 person-years
in those with normal cognition (p<0.001) in the years prior to the outcome
date. Conclusions: Our findings suggest an increased risk of dementia after
surgery with general anesthesia among older adults. If confirmed, this in-
creased risk for dementia may be an important factor to consider when making
decisions about surgery, especially those that are elective, in later life.
P3-154 PROSPECTIVE STUDY OF DIABETES AND
COGNITIVE DECLINE AND DEMENTIA SUBTYPES
IN CACHE COUNTY, UTAH, USA
Ronald G. Munger1, Jack Charoonruk2, JoAnn Tschanz1, Peter Zandi3,
Christopher Corcoran1, Heidi Wengreen1, Kate Hayden4, Maria Norton1,
Kathleen Welsh-Bohmer4, 1Utah State University, Logan, UT, USA;2Mahidol University, Bangkok, Thailand; 3The Johns Hopkins University,
Baltimore, MD, USA; 4Duke University, Durham, NC, USA.Contact e-mail: [email protected]
Background: Type 2 diabetes mellitus (DM) is a well-known cause of vas-
cular disease and cognitive impairment, but its relationship with specific sub-
types of dementia, including Alzheimer’s disease, is unclear. Methods: The
Cache County Memory Study (CCMS) is a prospective study of 5092 men
and women aged 65þ years at baseline in 1995. Cognitive function was as-
sessed with the Modified Mini-Mental State Examination (3MS) at baseline
and 3, 7, and 11 years later. Dementia was assessed by clinical examination
and standard diagnostic criteria. Diabetes history was self-reported and per-
sons with dementia at baseline were excluded from the analyses. Multivari-
able mixed effects models were used to evaluate differences in 3MS scores
and Cox proportional hazards models were used to evaluate risk of all-cause
mild cognitive impairment (MCI), all-cause dementia, and dementia sub-
types. Results: DM was associated with a lower mean 3MS score at baseline
(-0.92 points, p< 0.01) that was maintained over all examination waves. DM
was associated with risk of all-cause MCI (hazard ratio (HR) ¼ 1.57; 95%
confidence interval (CI) ¼ 1.24, 1.98) and all-cause dementia (HR ¼ 1.49,
CI¼ 1.13, 1.97). A stronger association was found between DM and the de-
mentia subgroup consisting of AD þ vascular diseases and vascular demen-
tia (HR ¼ 2.93, CI ¼ 1.94, 4.43). These results did not differ by sex. No
significant overall association was found between DM and risk of AD in
the absence of vascular disease (HR¼ 1.26, CI¼ 0.89, 1.78) however a dif-
ference was found by sex with a positive association for men (HR¼ 2.25; CI
¼ 1.24, 4.08) and no association for women (HR ¼ 1.10, CI ¼ 0.63, 1.93).
Conclusions: DM was associated with lower 3MS scores, MCI, all-cause de-
mentia, and dementia with vascular disease in the Cache County Memory
Study. AD in the absence of vascular disease was associated with DM in
men but not women. DM appears to primarily contribute to age-related cog-
nitive disorders via vascular mechanisms. In the absence of vascular disease,
DM may have more subtle neurodegenerative effects via non-vascular mech-
anisms that vary by sex.
P3-155 CEREBRAL BLOOD FLOW, WHITE MATTER
LESIONS AND RISK OF HIPPOCAMPAL ATROPHY:
THE SMART-MR STUDY
Mirjam I. Geerlings, Arnoud J. G. Knoops, Auke P. A. Appelman,
Theo D. Witkamp, Yolanda Van Der Graaf, Willem P. T. M. Mali, UniversityMedical Center Utrecht, Utrecht, Netherlands. Contact e-mail:
Background: Reduced cerebral blood perfusion and white matter lesions
(WML) may increase risk for Alzheimer’s disease. It has been suggested
that particularly the hippocampus is vulnerable to hypoperfusion and ische-
mia. We investigated whether total parenchymal cerebral blood flow (pCBF)
and WML increased risk for hippocampal atrophy in a population of patients
with atherosclerotic disease. Methods: Within the SMART-MR (Second
Manifestations of ARTerial disease-magnetic resonance) study, a cohort
study among patients with a history of atherosclerotic disease, cross-sectional
analyses were performed in 392 patients (mean age 6269 years, 84% male).
Automated brain segmentation was used to quantify volumes of WML and
total brain on MRI. Using MR angiography, CBF was measured in the inter-
nal carotid arteries and basilar artery and was expressed per 100 ml brain vol-
ume. Manual volumetric measurements of the hippocampus were performed
on a 3-dimensional T1-weighted MRI scan. Volumes of total hippocampus,
WML and total brain were expressed relative to intracranial volume. Results:
Total mean hippocampal volume was 6.260.7 ml. Mean pCBF was
49.8611.2 ml/min per 100 ml brain volume, and median WML volume
was 1.26 ml (10-90% 0.41-7.41). Linear regression analysis showed that re-
duced parenchymal CBF was not associated with smaller hippocampal vol-
ume after adjustment for age and sex, nor after additional adjustment for
vascular risk factors, lacunar infarcts and WML (b¼ 0.02 ml per SD decrease
in pCBF; 95% CI -0.05 to 0.93). Higher WML volume was associated with
smaller hippocampal volume after adjustment for age, sex, and attenuated but
remained statistically significant after additional adjustment for smoking, al-
cohol use, body mass index, hyperlipidemia, blood pressure, diabetes melli-
tus and lacunar infarcts (b¼ -0.08; 95% CI -0.153 to -0.002). However, after
adjustment for global brain atrophy, WML were no longer associated with
hippocampal volume (b¼ -0.06; 95% CI -0.127 to 0.018). Conclusions: Re-
duced parenchymal blood flow was not associated with smaller hippocampal
volumes in this population. WML were associated with smaller hippocampal
volumes, independent of shared vascular risk factors, but there was no evi-
dence of increased hippocampal volume loss compared to other brain tissue.
These findings do not suggest that the hippocampus in particular is vulnerable
to hypoperfusion and ischemia.
