Featured Research Sessions: F5-01: Subjective Cognitive Decline in Preclinical Alzheimer’s DiseaseP824

FEATURED RESEARCH SESSIONS: F5-01:

SUBJECTIVE COGNITIVE DECLINE IN PRECLINICAL

ALZHEIMER’S DISEASE

F5-01-01 A CONCEPTUAL FRAMEWORK OF SUBJECTIVE

COGNITIVE DECLINE (SCD) IN PRECLINICAL

ALZHEIMER’S DISEASE (AD)

Frank Jessen, University of Bonn, Bonn, Germany. Contact e-mail: frank.

jessen@ukb.uni-bonn.de

Background: Biomarker-based early recognition research in AD is moving

to the preclinical stage. One challenge is identifying individuals, which are

at increased risk of having preclinical AD and of progressing to dementia.

Growing evidence suggest that the self-experienced decline in cognitive per-

formance in elderly subjects with otherwise normal performance on cogni-

tive tests (subjective cognitive decline, SCD) is a risk factor for future AD

dementia and indicates an increased likelihood for the presence of preclin-

ical AD in individuals. A major limitation for further refinement of SCD as

an indicator of preclinical AD is the lack of a common framework and com-

mon research standards on this topic. Methods: In November 2012 the

SCD-Initiative (SCD-I) was founded to develop a common framework on

the research on SCD in preclinical AD. The working group includes main

authors of the recently presented criteria of preclinical AD, MCI due AD

and prodromal AD as well a main investigators of prominent biomarker ini-

tiatives (ADNI, AIBL, DESCRIPA, Dementia Competence Network) and

large population-based cohort studies. In a number of e-mail discussions

the common research framework was developed. Results: The group con-

cludes that the currently available data is too limited and too heterogeneous

to define SCD in preclinical AD as a clear-cut entity and highlights the need

for intensified research on this topic. The SCD-I created a research frame-

work which defines terminology and provides guidance on the coding of

on key features of SCD in research projects. Thus, it allows the integration

of a wide variety of research approaches in different settings and cohorts and

achieves comparability across different studies. The core components of the

framework will be presented in the session. Conclusions: The research

framework sets the stage for intensified and comparable research on

SCD in preclinical AD. It provides the basis to investigate characteris-

tics and dynamics of the earliest symptomatic stage of AD and to even-

tually evaluate the usefulness of SCD as a clinical sign of the

biomarker based diagnosis of preclinical AD.

F5-01-02 CSF BIOMARKERS AND APOE GENOTYPE

AS PREDICTORS OF CLINICAL PROGRESSION

IN PATIENTS WITH SUBJECTIVE COMPLAINTS

Wiesje Van der Flier, VU University Medical Center, Amsterdam,

Netherlands. Contact e-mail: wm.vdflier@vumc.nl

Background: We investigated the independent and combined predictive

value of CSF biomarkers and APOE genotype for clinical progression in pa-

tients with subjective complaints.Methods:We included 229 patients with

subjective complaints (6169 yrs; 93(41%) F;MMSE 2862) from our mem-

ory clinic based Amsterdam Dementia Cohort. Patients were eligible when

CSF biomarkers, APOE genotype and follow-up (m6sd; 362yrs) were

available. After follow-up, 192 patients remained stable, 21 progressed to

MCI and 8 developed AD. Five patients progressing to non-AD dementia

were not included in further analyses. Clinical progression was defined as

patients progressing to MCI or AD. Predictive value of dichotomized CSF

biomarkers and APOE genotype were assessed using Cox proportional haz-

ard models adjusted for age, sex and MMSE. Results: Patients showing

clinical progression (n¼29(13%)) were older than patients who remained

stable. There were no differences in sex or MMSE. They were more often

APOE e4 carrier (62% vs 38%; p<0.05). CSF levels were lower in patients

who showed clinical progression for ab42 and higher for (p)tau (ab42

6396290 vs 8646227; tau 4506253 vs 2776191; ptau 66631vs 48621;

all p<0.01). Overall, APOE e4 carriers had lower ab42 and higher (p)tau

than APOE e4 non-carriers (all p<0.05). APOE e4carriers had a more than

twofold increased risk of clinical progression (HR (95% CI): 2.2 (1.0-4.8)).

For the CSF biomarkers, abnormal ab42 was associated with the highest in-

creased risk (HR (95% CI): 6.6 (3.0-14.6)), followed by tau (4.3 (1.9-9.8))

and ptau (2.8 (1.3-6.4)). Therewas a significant interaction betweenAPOEge-

notype and CSF ab42 (p<0.05), but not betweenAPOEgenotype and CSF tau

or ptau. After stratification for APOE, CSF ab42 had the strongest

predictive value in APOE e4 noncarriers (HR (95% CI): 35 (6-217)), while

the predictive value in APOE e4 carriers was modest (3.1 (1.1-8.4)).

Conclusions: In patients with subjective complaints, a subset of which has

preclinical AD, CSF ab42 is the strongest predictor of clinical progression, es-

pecially inAPOE e4 noncarriers. This finding illustrates that the effect of beta-

amyloid 42 at least partially follows a different, not APOE-related pathway.

F5-01-03 NEUROPSYCHOLOGICAL AND NEUROIMAGING

DIFFERENCES BETWEEN INDIVIDUALS WITH

SUBJECTIVE COGNITIVE DECLINE RECRUITED

FROM MEMORY CLINIC VERSUS FROM THE

GENERAL POPULATION

Audrey Perrotin, Inserm - EPHE - UCBN U1077, Caen, France. Contact

e-mail: audrey.perrotin@gmail.com

Background: Subjective cognitive decline (SCD) may be the first clinical

sign of Alzheimer disease (AD). A recent initiative aimed at further defining

the SCD concept in relation to preclinical AD. Within this framework, the ob-

jective of the present study was to assess the relevance of the setting in select-

ing SCD individuals with high likelihood to develop AD.Methods:A total of

51 elderly without objective cognitive deficits were included in the study, on

which 10 were recruited from a memory clinic (SCD-clinic), 21 were elderly

from the general populationwith a high self-rating on the “MacNair” Cognitive

Difficulties Scale (SCD-population), and 20 were controls with low rating on

the MacNair. Data from detailed neuropsychological assessment, structural-

MRI, FDG-PETand amyloid Florbetapir-PETwere acquired and compared be-

tween groups. Results: No significant difference was found between the three

groups regarding demography andApoE4 genotyping. As expected, both SCD-

clinic and SCD-population showed higher self- and informant-ratings on the

MacNair compared to the controls, but the two groups didn’t differ from one

another. No difference was found in any neuropsychological test between the

three groups. Regarding neuroimaging biomarkers, highly significant differ-

ences were found in the SCD-clinic compared to controls or SCD-population

in the hippocampal region, including both graymatter atrophy and hypometab-

olism. By contrast, the SCI-population didn’t show any significant difference

compared to controls but their MacNair rating tended to positively correlate

with atrophy, including (but not only) within the hippocampal region. SCD

was relatedwith Florbetapir-PETmeasurement in the frontal cortex but this ef-

fect cancelled when controlling for ApoE4 genotype. Conclusions: Our find-

ings showed that, among two SCD groups without objective deficits and same

degree of subjective cognitive decline, only those who seek help for memory

concern showed significant atrophy, with a topography consistent with early

AD. In line with studies showing that worries associated with SCD increase

the risk for AD, these findings highlight the relevance of memory clinic set-

ting in selecting SCDwith a high likelihood of developing AD. The degree of

subjective cognitive decline in the general populationmay also be relevant but

is probably associated to a more heterogeneous outcome.

F5-01-04 SUBJECTIVE COGNITIVE CONCERNS AS AN

EARLY INDICATOR OFALZHEIMER’S DISEASE

PATHOLOGY

Rebecca Amariglio, Massachusetts General Hospital, Boston,

Massachusetts, United States. Contact e-mail: RAMARIGLIO@partners.

org

Background:Although self-reported cognitive concerns (SCC) have previ-

ously been dismissed as a sign of the “worried well”, there is emerging ev-

idence to suggest that SCC may herald initial cognitive decrements at the

stage of preclinical Alzheimer’s disease (AD). Recent preliminary data

from our own group and others suggests that specific SCC may in fact indi-

cate early awareness prior to objective impairment on standardized tests and

may be associated with evidence of early pathology on AD biomarkers.

Methods:Multimodality studies relating SCCwith AD biomarker evidence