Abstract Details

Title Early Behavioral Changes in Familial Alzheimer's Disease: Results from the Dominantly Inherited Alzheimer Network

Topic Aging and Dementia

Presentation(s) S24 - (-)

Poster/Presentation
Number 005

Objective

Background AD pathology begins 15-20 years before overt symptoms. Prior studies indicate psychiatric symptoms such as anxiety and depression are either early signs of or risk factors for the development of AD. Persons at 50% risk for inheriting FAD mutations allow us to identify early behavioral changes.

Design/Methods The first 212 subjects enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at 50% risk for FAD, were evaluated with the Neuropsychiatric Inventory-Q (NPI-Q), the 15-item Geriatric Depression Scale (GDS) and the Clinical Dementia Rating Scale (CDR). Asymptomatic (CDR = 0), mildly symptomatic (0.5), and overtly affected (CDR > 0) FAD mutation carriers (MCs) were compared to non-carriers (NCs) with regard to frequency of behavioral changes on the NPI-Q (chi-square test), and depression severity on the GDS (two-sided t-test).

Results 133 subjects were MCs and 79 were NCs. Among MCs, 75 had CDR scores of 0, 37 scores of 0.5, and 21 scores > 0.5. There were no differences between asymptomatic MCs and NCs in neuropsychiatric symptoms. Among MCs with CDR scores of 0.5, there was a significantly higher frequency of agitation (30% vs. 4%), apathy (41% vs. 3%), appetitive changes (30% vs. 9%), depressive symptoms (49% vs. 15%), disinhibition (16% vs. 1%), irritability (51% vs. 10%), and sleep changes (32% vs. 4%) than in NCs. Mean GDS score was elevated in mildly symptomatic MCs (3.7 vs. 1.1). Among demented MCs, the frequency of most behavioral symptoms and mean GDS scores were higher than in NCs.

Conclusions Robust behavioral changes are not common in presymptomatic FAD. Increases in agitation, apathy, disinhibition, irritability, sleep behaviors and depression can accompany early cognitive changes. These findings are consistent with observations in late-onset AD.

Authors/Disclosures
John M. Ringman, MD, FAAN (Keck School of Medicine of USC, Neurology Dept) PRESENTER	The institution of Dr. Ringman has received research support from Avid Pharmaceuticals. The institution of Dr. Ringman has received research support from AltaMed. The institution of Dr. Ringman has received research support from CurePSP.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Alison Goate, PhD (WA Univ Sch of Medicine)	No disclosure on file
	No disclosure on file
	No disclosure on file
Tammie Benzinger (Washington University)	Tammie Benzinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $0-$499 for serving as a Consultant for Sora Neuroscience. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol, Myers Squibb. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for PeerView. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medscape. The institution of Tammie Benzinger has received research support from Siemens. The institution of Tammie Benzinger has received research support from Hyperfine. Tammie Benzinger has a non-compensated relationship as a Consultant with Siemens that is relevant to AAN interests or activities. Tammie Benzinger has a non-compensated relationship as a Consultant with Eisai that is relevant to AAN interests or activities.
	No disclosure on file
Chengjie Xiong, PhD (Washington University School of Medicine)	Chengjie Xiong has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for DIADEM.
Bernardino Ghetti, MD (Indiana University School of Medicine)	No disclosure on file
Eric M. McDade, DO (Washington University At St. Louis School of Medicine)	Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. McDade has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzamend. Dr. McDade has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fondation Alzheimer. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. The institution of Dr. McDade has received research support from NIA. The institution of Dr. McDade has received research support from Eli Lilly. The institution of Dr. McDade has received research support from Hoffman-La Roche. The institution of Dr. McDade has received research support from Eisai. The institution of Dr. McDade has received research support from Eisai. Dr. McDade has received intellectual property interests from a discovery or technology relating to health care. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Fondation Alzheimer.
	No disclosure on file
Richard P. Mayeux, MD, MSc, FAAN (The Neurological Institute, Columbia University Medical Center)	Dr. Mayeux has nothing to disclose.
Martin N. Rossor, MD, FAAN (University College London)	No disclosure on file
Reisa A. Sperling, MD (Brigham and Women'S Hospital)	Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nervgen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oligomerix. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vaxxinity. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Sperling has received research support from Eli Lilly. The institution of Dr. Sperling has received research support from Eisai. The institution of Dr. Sperling has received research support from NIH.
Stephen P. Salloway, MD, MS (Brown Medical School)	Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lilly. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NovoNordisk. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prothena. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurophet. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kisbee. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CognitionRX. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Icometrix. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck.
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System)	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Randall Bateman, MD (Washington Univ School of MedicinE)	Dr. Bateman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for C2N Diagnostics . Dr. Bateman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for C2N Diagnostics . Dr. Bateman has received stock or an ownership interest from C2N Diagnostics. The institution of Dr. Bateman has received research support from Alzheimer's SILQ Research Fund/ Barnes Jewish Hospital Foundation . The institution of Dr. Bateman has received research support from National Institutes of Health- R21AG067559. The institution of Dr. Bateman has received research support from Centene Corporation. The institution of Dr. Bateman has received research support from Rainwater Charitable Foundation . The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Anonymous Foundation. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from BrightFocus Foundation. The institution of Dr. Bateman has received research support from Assn for Frontotemporal Degeneration FTD Biomarkers Initiative. The institution of Dr. Bateman has received research support from Rainwater Foundation. The institution of Dr. Bateman has received research support from NIH- R01NS095773. The institution of Dr. Bateman has received research support from AbbVie/Biogen/Eli Lilly. The institution of Dr. Bateman has received research support from NIH/NINDS/NIA- RF1AG061900 (R56AG061900 & R01NS065667). The institution of Dr. Bateman has received research support from Eisai. The institution of Dr. Bateman has received research support from Good Ventures Foundation. The institution of Dr. Bateman has received research support from National Institutes of Health- R01 AG070941. The institution of Dr. Bateman has received research support from National Institutes of Health-. The institution of Dr. Bateman has received research support from National Institutes of Health. The institution of Dr. Bateman has received research support from NIH- P50AG005681-36. The institution of Dr. Bateman has received research support from NIH/NIA- U19AG032438. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Pharma Consortium. The institution of Dr. Bateman has received research support from Eli Lilly . The institution of Dr. Bateman has received research support from NIH/NIA- NIH R01AG053267. The institution of Dr. Bateman has received research support from Administrative Supplement 01- NIH . The institution of Dr. Bateman has received research support from Administrative Supplement 02- NIH . The institution of Dr. Bateman has received research support from NIH- 1U01AG059798. The institution of Dr. Bateman has received research support from NIH- R01AG068319. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Roche. The institution of Dr. Bateman has received research support from NIH/NIA- R01AG046179. The institution of Dr. Bateman has received research support from GHR; Anonymous Foundation. The institution of Dr. Bateman has received research support from NIH/NIA- 1U01AG042791, 1U01AG042791. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from NIH/State Government- 5U19AG010483. Dr. Bateman has received intellectual property interests from a discovery or technology relating to health care.
John C. Morris, MD, FAAN (Washington University)	Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CBR International Advisory Board. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cure Alzheimers Fund. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LEADS Steering Commitee. The institution of Dr. Morris has received research support from NIH grants. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care.

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