Oral Sessions: O3-12: Public Health and Psychosocial Focus: MCI and Dementia—Attitudes, Beliefs and Perceptions P545
both overall, and stratified by APOE-ε4 (+/-). Results: The prevalence of
FBB+ was significantly higher in the highest tertile of PROCAM, (7/27,
25.9%) compared with first and second tertiles (2/26 and 2/25 respectively,
p<0.05). FBB SUVR distribution differed significantly according to PRO-
CAM tertile (p¼0.03), in all participants, and in APOE-ε4+ (p¼0.02), but
not APOE-ε4- (Figure 1). There was no significant difference in age be-
tween PROCAM tertiles. There was no significant difference in FBB
SUVR between tertiles of FCRP. Conclusions: To our knowledge this is
the first study to find a significant association was observed between a com-
posite vascular risk measure (PROCAM) taken in mid-life and, and in vivo
beta-amyloid burden later in life, a finding which persisted in APOE-ε4+ but
not APOE-ε4- participants. However, no association was seen with the
FCRP. Incorporation of later-life biomarkers such as beta-amyloid burden
measured with FBB-PET into a cohort established in mid-life increases
the ability to shed new light on relevant risk factors associated with AD
across the life-course. Further work will address whether overall burden
of mid-life vascular risk, or specific individual components of the PROCAM
are implicated in this association with late-life beta-amyloid.
O3-11-05 ATHEROSCLEROTIC CALCIFICATION IS
RELATED TO COGNITIVE DECLINE
Meike Vernooij, Daniel Bos, Albert Hofman, Jacqueline Witteman,
Aad van der Lugt, Mohammad Ikram, Erasmus Medical Center, Rotterdam,
Netherlands. Contact e-mail: [email protected]
Background: Increasing evidence implicates atherosclerosis in the etiology
of cognitive impairment and ultimately dementia, but longitudinal data are
scarce. Also, it remains unclear whether atherosclerosis in different vessel
beds affects cognitive decline differentially. In this study, we investigate
the relationship between arterial calcification, as marker of atherosclerosis,
in four vessel beds and cognitive decline over a 6 year interval. Methods:
From the population-based Rotterdam Study, 1858 participants (mean age
68.46 5.9 years) underwent computed tomography of the coronaries, aortic
arch, extracranial and intracranial carotid arteries to quantify atherosclerotic
calcification. At baseline and after six years of follow-up, cognition was
assessed using the MMSE and a neuropsychological test battery that com-
prised the following domains: global cognition, memory, executive function
and information processing speed. Per participant, we calculated the differ-
ence between both time points in standardized scores for each cognitive
domain. Relationships between atherosclerotic calcification and cognitive
decline were assessed using linear regression models and adjusted for
age, sex, education and additionally for APOE-ε4-status and cardiovascular
risk factors. Results: Larger load of calcification in the coronary arteries,
aortic arch and intracranial carotid arteries, but not in the extracranial ca-
rotid arteries, was associated with a decline in MMSE scores and decline
in global cognitive function (see Figure). These associations seemed primar-
ily driven by decline in executive function. Conclusions: Atherosclerosis is
an important cause of cognitive decline and thus of interest as potential
modifiable target for prevention of dementia.
O3-11-06 RETINALVESSEL CALIBERS ASSOCIATE
DIFFERENTIALLY WITH GREY MATTER AND
WHITE MATTER ATROPHY ON MRI
Mohammad Ikram1, Frank Jan Jong1, Mohammad Kamran Ikram2,
Meike Vernooij1, Wiro Niessen1, Caroline Klaver1, Aad van der Lugt1,
Albert Hofman1, 1Erasmus Medical Center Rotterdam, Rotterdam,
Netherlands; 2Singapore Eye Research Institute (SERI), Singapore,
Singapore. Contact e-mail: [email protected]
Background:Normal aging as well as Alzheimer’s disease is characterized
by diffuse accumulation of cerebral pathologies that can ultimately lead to
brain atrophy. Cerebral small vessel disease is thought to contribute to brain
atrophy, but it remains unclear whether it affects grey matter and white mat-
ter atrophy differentially. Given the shared embryologic origin of retinal and
cerebral microcirculation, imaging of retinal vessels provides a direct mea-
sure to study cerebral small vessel disease in vivo. We studied the associa-
tion of retinal vascular calibers with brain atrophy, focusing particularly on
grey matter and white matter atrophy separately.Methods: In 1,065 non-de-
mented and stroke-free persons (mean age 67.5 and 51% women) from the
population-based Rotterdam Study, we performed retinal imaging and brain
MRI. Retinal arteriolar and venular calibers were semi-automatically mea-
sured on digitized fundus transparencies. Using automated MRI-quantifica-
tion we obtained whole-brain volume and volumes of grey matter and white
matter. The association of retinal vessels with brain tissue volumes was as-
sessed continuously and in quintiles, while adjusting for age, sex, the other
retinal vessel (arterioler vs. venules) and additionally for cardiovascular risk
factors. Results: Both narrower arteriolar and wider venular calibers were
associated with smaller brain volume, independent from each other, both
in continuously and in quintiles. These associations were primarily driven
by smaller white matter volume (difference in Z-score per SD increase in
retinal vessel: 0.07 (95%CI 0.01;0.14) for arterioles and -0.09 (-0.15;-0.02
for venules), whilst no associations were seen for grey matter (difference
in Z-score -0.02 (-0.07;0.03) for arterioles and 0.04 (-0.03;0.11) for ve-
nules). Adjustments for cardiovascular risk factors marginally attenuated
the results, but wider venular caliber remained significantly associated
with smaller white matter volume (-0.07 (-0.14;0.00)).To rule out any effect
of white matter lesions driving these associations, we performed the analy-
ses for both normal white matter and total white matter, but results remained
identical. Conclusions: We found that narrower arterioles and wider ve-
nules are related to white matter atrophy, but not grey matter atrophy.
This suggests that small vessel disease primarily leads to white matter atro-
phy, providing further insights into how cerebral small vessel disease may
ultimately affect the risk of Alzheimer’s disease.
ORAL SESSIONS: O3-12
PUBLIC HEALTH AND PSYCHOSOCIAL FOCUS: MCI AND
DEMENTIA—ATTITUDES, BELIEFS AND PERCEPTIONS
O3-12-01 AN INTERNET-BASED SURVEYASSESSING
PUBLIC ATTITUDES ABOUT PRECLINICAL
TESTING FOR ALZHEIMER’S DISEASE
Richard Caselli1, Jessica Langbaum2, Gary Marchant3, Rachel Lindor3,
Katherine Hunt1, Jason Robert4, 1Mayo Clinic, Scottsdale, Arizona, United
States; 2Banner Alzheimer’s Institute, Phoenix, Arizona, United States;3Sandra Day O’Connor College of Law, Arizona State University, Tempe,
Arizona, United States; 4School of Life Sciences, Arizona State University,
Tempe, Arizona, United States. Contact e-mail: [email protected]
Background: Preclinical testing for Alzheimer’s disease (AD) in which
predictive tests are performed before symptoms develop has materialized,
and interest among both professionals and the general public is rising.
Research programs such as the REVEAL study have shown that presymp-
tomatic disclosure of APOE genotype, which predicts a person’s risk of de-
veloping AD, can be done safely under carefully supervised conditions, but
the perspectives and desires of the general public remain to be explored, es-
pecially regarding other types of testing options. Methods: Information
about preclinical testing, and an online survey posted on the Alzheimer’s
Oral Sessions: O3-12: Public Health and Psychosocial Focus: MCI and Dementia—Attitudes, Beliefs and PerceptionsP546
Prevention Registry website (www.endALZnow.org) provided us the
opportunity to determine levels of interest in the general population for pre-
symptomatic testing and to correlate interest with basic demographic char-
acteristics. Results: Of 2135 total respondents in its first month, 99% were
high school graduates and 70%were college graduates. 68.5%were self-de-
scribed as professional, and another 21% as managers or self-employed.
92.7% reported a parent and 58.8% a sibling with AD. Fear of AD
(80.6%) exceeded cancer (12%), stroke (5.3%), and heart attack (2.1%).
80% wanted genetic testing if paid by insurance; 54% if it would cost
them at least $100. The most common reasons for not wanting genetic test-
ing were personal fear of the possible results (29.6%) and fear it might hurt
their insurability (15.7%). 78.2% stated they would want biomarker testing
(mainly PET but not spinal taps) to detect signs of AD years before the onset
of symptoms even in the absence of an effective prevention therapy. If found
to be at high risk for Alzheimer’s disease, 13.2% would “seriously consider
suicide,“ 18.8% would spend all their money doing what they always
wanted. 75.7%would obtain long term care insurance and 89.2%would pur-
sue a healthier lifestyle. The implications of a positive APOE test were in-
correctly understood by 12.7%; and 17.6% would interpret a positive
biomarker test as evidence of having AD now. Conclusions: Responders
were highly educated, specifically interested in AD, and generally wanting
preclinical testing. However over 10% misunderstand the implications of
genetic and biomarker testing, and over 10% would “seriously consider
suicide” if given “bad news.”
O3-12-02 PERSPECTIVES ON THE BENEFITS AND HARMS
OF PRECLINICALTESTING FOR ALZHEIMER’S
DISEASE
Jalayne Arias1, Paul Ford1, Richard R. Sharp1, Alexander Rae-Grant1,
Jeffrey Cummings2, 1Cleveland Clinic, Cleveland, Ohio, United States;2Cleveland Clinic Lou Ruvo Center, Las Vegas, Nevada, United States.
Contact e-mail: [email protected]
Background: Patient and family perspectives regarding potential bene-
fits or harms of beta-amyloid biomarkers for Alzheimer’s disease in
asymptomatic individuals are currently unknown. Recently published
criteria deem the use of PET amyloid for asymptomatic individuals in-
appropriate at this time point. Yet, consideration of patient and family
member perspectives is critical as clinicians and researchers contemplate
asymptomatic testing. A positive amyloid test could have psychological,
financial, legal and social consequences for patients and families. Pa-
tient and family perspectives (including goals, values, and concerns)
will serve an important role in determining the potential benefit of pre-
clinical information. This exploratory study identifies core themes relat-
ing to family members’ perspectives about potential benefits and harms
of asymptomatic testing for biomarkers associated with Alzheimer’s dis-
ease. Methods: 14 semi-structured interviews were conducted and ana-
lyzed for family members of patients diagnosed with Alzheimer’s
dementia or mild cognitive impairment. Using inductive qualitative
methods investigators analyzed recorded and transcribed interviews to iden-
tify themes given by interviewees including whether participants classified
knowing of a preclinical status as beneficial. Research was conducted with
IRB approval.Results:Half of the participants reported that preclinical test-
ing would be beneficial, where beneficial is defined as the potential benefits
of knowing the information would outweigh potential harms. Participants
identifying potential benefits focused on what they could do with the infor-
mation. Classification of benefits included themes of seeking treatment, al-
tering lifestyle, and preparation for loss of cognition. Participants
identifying harm focused on the psychological impact of the information.
Classification of potential harms included worry, anxiety, or depression.
Life philosophy and experiences shaped participants’ perspectives.Conclu-
sions: Family members provide unique insight into how potential benefits
and harms may relate to patient and family outcomes. These outcomes
and patient and family perspectives should be foundational to implementing
clinical amyloid testing in asymptomatic individuals. These perspectives
can inform: (1) the importance of treatment options in justifying asymptom-
atic testing, (2) the informed consent process, and (3) the disclosure process.
O3-12-03 THE PSYCHOLOGICAL IMPACT OF GENETIC
RISK INFORMATION ON INDIVIDUALS WITH
MILD COGNITIVE IMPAIRMENTAT IMMINENT
RISK FOR CONVERSION TO ALZHEIMER’S
DISEASE DEMENTIA: FINDINGS FROM THE
REVEAL STUDY
Kurt Christensen1, Scott Roberts2, Jason Karlawish3,
Thomas Obisesan4, Leo Waterston5, L. Adrienne Cupples6,
Wendy Uhlmann7, Elisabeth Wood8, Robert Green9, 1Brigham and
Women’s Hospital and Harvard Medical School, Boston, Massachusetts,
United States; 2University of Michigan School of Public Health, Ann
Arbor, Michigan, United States; 3University of Pennsylvania,
Philadelphia, Pennsylvania, United States; 4Howard University Hospital,
Washington, District of Columbia, United States; 5Brigham and Women’s
Hospital, Boston, Massachusetts, United States; 6Boston University
School of Public Health, Boston, Massachusetts, United States;7University of Michigan Health System Division of Molecular Medicine &
Genetics, Ann Arbor, Michigan, United States; 8University of
Pennsylvania Center for Neurodegenerative Disease Research,
Philadelphia, Pennsylvania, United States; 9Brigham and Women’s
Hospital, Harvard Medical School, and Partners Center for Personalized
Genetic Medicine, Boston, Massachusetts, United States.
Contact e-mail: [email protected]
Background: Given advances in AD treatment, APOE genotyping may aid
clinical practice by identifying patients at different levels of risk for AD con-
version. Prior work showed that AD genetic risk information did not pose
psychological risks to volunteer populations who are many years away
from disease onset, but little is known about its impact on MCI patients at
substantially increased risk of AD conversion in the near future or their
care partners.Methods:Amnestic MCI patients were randomized to re-
ceive 3-year AD risk estimates (range: 8-57%) based on age and MCI
diagnosis alone, or based on those factors and APOE genotype. To
date, 6-week follow-up data has been collected from 61 patients
(mean age 72; 46% male; 18% Black) and study partners (typically
a spouse or adult child, mean age: 64, 32% male, 16% Black). Anx-
iety and depression were assessed using short forms of the State-Trait
Anxiety Inventory (STAI) and the Geriatric Depression Rating Scale
(GDRS). Test-related distress was assessed using the Impact of
Events Scale (IES). Results: Among patients, 6-week mood scores
were substantially below cutoffs for concern for both the genotyped
group (STAI¼11.7, GDRS¼1.9, IES¼11.4) and control group
(STAI¼11.9, GDRS¼2.7, IES¼15.7). Differences in changes to
STAI and GDRS scores by randomization arm or genotype were
not observed. However, IES scores 3-days post-disclosure were
greater among ε4-positive patients than control arm patients
(D¼5.9, p¼.04) and ε4-negative patients (D¼7.3, p¼.02), while dif-
ferences were not observed at the 6-week follow-up. Among study
partners, differences to changes in STAI and GDRS scores were
not observed by randomization arm, but IES scores of ε4-positive pa-
tients were greater than ε4-negative patients 3-days post-disclosure
(D¼8.4, p¼.01). Differences in IES scores by randomization arm
or patient genotype among study partners were not observed at the
6-week follow-up. Conclusions: Genetic risk information about immi-
nent AD conversion does not pose significant short-term psychological
risks to MCI patients or study partners. Test-related distress in the imme-
diate aftermath of risk disclosure was greater among ε4-positive partici-
pants and study partners, but this effect was transient. Results are
consistent with prior work on healthy adults, and extend those findings
to potential caregivers.
O3-12-04 USING A COMMON SENSE MODELTO PREDICT
WILLINGNESS TO BE SCREENED FOR MILD
COGNITIVE IMPAIRMENT IN A COMMUNITY
SAMPLE OFAFRICAN-AMERICANS
Carey Gleason1, Wade Gunn2, Rachel Smedley3, Sanjay Asthana4,
Dorothy Edwards2, 1Wisconsin Alzheimer’s Disease Research Center,
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