Alexa Pichet Binette

Proximity to Parental Symptom Onset and Amyloid-β Burden in Sporadic Alzheimer Disease

Importance Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. Objective To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-&bgr; (A&bgr;) levels in asymptomatic individuals with a parental history of AD dementia. Design, Setting, and Participants This cohort study analyzed A&bgr;1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant’s proximity to his/her parent’s symptom onset by subtracting the index relative’s onset age from his/her current age. The association between proximity to parental symptom onset and A&bgr; levels was then assessed using apolipoprotein E &egr;4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11–labeled positron emission tomography (PIB-PET) A&bgr; biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. Main Outcomes and Measures The association between proximity to parental symptom onset and A&bgr; burden in asymptomatic individuals with a parental history of sporadic AD. Results The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent’s onset age had lower CSF A&bgr;1-42 levels (range, 402-1597; B = −9.09, P = .04). This association was stronger in APOE4 carriers (B = −17.9, P = .03) and women (B = −19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. Conclusions and Relevance These results suggest that proximity to parental symptom onset may help estimate A&bgr; biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.

NEUROPSYCHIATRIC BURDEN IS RELATED TO INCREASED AMYLOID BUT NOT TAU DEPOSITION IN LATE MIDDLE-AGED COGNITIVELY NORMAL INDIVIDUALS WITH A FAMILY HISTORY OF ALZHEIMER’S DISEASE

as Free Recall>30 and Total (Cued) Recall>46; MMSE 27, Stage 1 was Free Recall 25-30 and Total Recall>46; MMSE 26, and Stage 2 was collapsed as either Free Recall 18-24 and Total Recall>44 or Total Recall 33-43 regardless of Free Recall score; MMSE 25. SOMI group differences in PET markers were explored. Results: A total of 66% were classified as SOMI Phase 0, 19%were Phase 1, 12%were Phase 2+ and 3%were unclassified (e.g., intact Free Recall with impaired Total Recall). A linear fit across Phase 0 to 2 was significant for Ab (p<0.001, Fig1), inferiortemporal (p<0.001, Fig2) and entorhinal Tau (p<0.001, Fig3). Posthoc contrasts revealed that Phase 1 had significantly higher levels of inferiortemporal Tau compared with Phase 0 (p<0.01), and that Phase exhibited greater inferiortemporal tau burden compared with Phase 0 (p<0.001). A similar but less robust pattern was observed with entorhinal Tau whereby the Phase 2 (p<0.001) had higher Tau compared with Phase 0 whereas Phase 1 and Phase 0 differed at trend level (p1⁄40.063).Conclusions:Higher stage of subtle objective memory impairment amongst clinically normal indi-

GENETIC AND ENVIRONMENTAL FACTORS ARE DIFFERENTIALLY RELATED TO Aβ BURDEN IN THE PRESYMPTOMATIC PHASE OF AUTOSOMAL DOMINANT AND SPORADIC ALZHEIMER’S DISEASE

Figure 1. Ab toms onset (E mutation carri history of spor lation in the tw while dotted l were obtained in ADAD, mu FACTORS ARE DIFFERENTIALLY RELATED TO Ab BURDEN IN THE PRESYMPTOMATIC PHASE OF AUTOSOMAL DOMINANTAND SPORADIC ALZHEIMER’S DISEASE Julie Gonneaud, Christophe Bedetti, Alexa Pichet Binette, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Judes Poirier, John C. S. Breitner, Sylvia Villeneuve, DIAN Study Group, and PREVENT-ADResearchGroup, McGill University, Montreal, QC, Canada; Douglas Mental Health Research Institute, Montreal, QC, Canada; Centre for Studies on Prevention of Alzheimer’s Disease, Douglas Mental Health Institute, Montreal, QC, Canada; Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Washington University School of Medicine, Saint Louis, MO, USA; Knight Alzheimer’s Disease Research Center, Saint Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA. Contact e-mail: gonneaud@cyceron.fr

NEUROPSYCHIATRIC BURDEN IS RELATED TO INCREASED AMYLOID BUT NOT TAU DEPOSITION IN COGNITIVELY NORMAL OLDER ADULTS

Dementia Behavior Study, caregivers were asked prior to randomized treatment assignment how much they would be willing to pay (WTP) per session for an 8-session program that lasts 3months, was delivered by healthcare professionals in their home, and provided them with skills to address problem behaviors of PwD and stress reduction techniques (response options:

EARLY INCREASE IN TAU-PET SIGNAL IS ASSOCIATED WITH Aβ BURDEN, CSF P-TAU LEVELS AND COGNITION IN COGNITIVELY NORMAL LATE-MIDDLE-AGED ADULTS

0/session,

SUBJECTIVE COGNITIVE DECLINE IS ASSOCIATED WITH ALTERED POSTERIOR CINGULATE CONNECTIVITY IN ELDERLY WITH A FAMILIAL HISTORY OF ALZHEIMER’S DISEASE

25/session,

MOVING AWAY FROM SINGLE AD-SIGNATURE ROI: ASSESSING THE RELATIONSHIP BETWEEN WHOLE-BRAIN GRAY MATTER PATTERN, AD PATHOLOGY, AND COGNITION IN HEALTHY ELDERLY AT RISK OF AD

50/session,

ASSESSING THE IMPACT OF INFLAMMATION ON LIMBIC CIRCUITRY AND ITS ROLE IN DEPRESSION IN OLDER ADULTS

75/ session,

HIGH CSF TAU IS RELATED TO REDUCED HIPPOCAMPAL VOLUME AND SUBJECTIVE COGNITIVE DECLINE IN HEALTHY ELDERLY WITH AMYLOID PATHOLOGY

100/session,

YEARS TO PARENTAL SYMPTOM ONSET PREDICTS AMYLOID BURDEN IN HEALTHY ELDERLY WITH A PARENTAL HISTORY OF SPORADIC ALZHEIMER’S DISEASE

125/session,