Abstract Details

Title Frequency of White Matter Hyperintensities Across Neurodegenerative Syndromes Compared to Cognitively Unimpaired Individuals

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-013

Objective To report the relationship between white matter hyperintensity (WMH) and cognitive impairment across the spectrum of Alzheimer’s Disease (AD), Lewy Body Disease (LBD), and Frontotemporal Lobar Degeneration (FTLD) compared to controls.

Background

WMH are well known imaging markers of brain microvascular disease associated with aging and cognition. WMH have also been associated with advanced neurodegenerative changes. However, there is limited information about WMH across the cognitive spectrum of AD, LBD, or FTLD syndromes. Consequently, it is unclear if WMH represent a risk factor to the development of cognitive impairment or represent sequela of neurodegeneration.

Design/Methods

We included Mayo Clinic Alzheimer’s Disease Research Center (ADRC) participants who were 50 or older with MRI. Cognitive status and diagnosis were determined by committee consensus employing existing criteria. WMH volume was estimated and scaled over total intracranial volume, with severe burden defined as ≥0.98% of total intracranial volume. Associations with log-transformed WMH were tested using linear regression, adjusted for age and sex. The covariates of interest were group (controls, AD, LBD, and FTLD) tested in the whole sample and global CDR tested using impaired participants. For severe WMH burden, we evaluated mean ages for each disease.

Results Our cohort included 1078 participants, 166 controls, 473 AD, 247 DLB, and 192 FTLD participants. When controlling for age and sex, each disease had higher logged-WMH than controls (AD: β=0.49 SE=0.08, DLB: β=0.33 SE=0.08, and FTD: β=0.63 SE=0.09; all p<0.001). CDR was positively associated with logged-WMH (β=0.44, SE=0.04, and p<0.001). For patients with severe WMH burden, average age (with SD) was higher in AD (77.0 +/- 7.3) and DLB (75.0 +/- 5.7) compared to FTD (70.0 +/- 8.5).

Conclusions

Differential expression of WMH across cognitive syndromes represents both a non-specific small vessel disease and neurodegeneration, which can serve as a marker of disease progression.

Authors/Disclosures
Camilo Bermudez, MD, PhD (Mayo Clinic) PRESENTER	Dr. Bermudez has nothing to disclose.
Angela Fought (Mayo Clinic)	Angela Fought has received personal compensation in the range of $500-$4,999 for serving as a Biostatistician on DSMB with Northwestern University.
Ekaterina Hofrenning, MS	Ms. Hofrenning has nothing to disclose.
Kejal Kantarci, MD (Mayo Clinic)	The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. The institution of Dr. Kantarci has received research support from Eisai. The institution of Dr. Kantarci has received research support from BioArctic.
Clifford R. Jack, Jr., MD (Mayo Clinic)	The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Bradley F. Boeve, MD, FAAN (Mayo Clinic)	Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
David T. Jones, MD (Mayo Clinic)	Dr. Jones has stock in Cephlodyne Neurotechnologies, Inc.. Dr. Jones has received intellectual property interests from a discovery or technology relating to health care.
David S. Knopman, MD, FAAN (Mayo Clinic)	Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
Hugo Botha, MD (Mayo School of Graduate Medical ��ɫ��, Rochester)	Dr. Botha has received research support from NIH. An immediate family member of Dr. Botha has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH.
Vijay K. Ramanan, MD, PhD (Mayo Clinic)	The institution of Dr. Ramanan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Daridorexant trial for AD prevention (funded by Weston Family Foundation). The institution of Dr. Ramanan has received research support from the National Institutes of Health. The institution of Dr. Ramanan has received research support from the Mangurian Foundation for Lewy Body Disease Research. The institution of Dr. Ramanan has received research support from as part of clinical trials sponsored by the Alzheimer's Association, Eisai, the Alzheimer's Treatment and Research Institute at USC, and Transposon Therapeutics, Inc.. The institution of Dr. Ramanan has received research support from Medscape. The institution of Dr. Ramanan has received research support from Expert Perspectives in Medicine. The institution of Dr. Ramanan has received research support from Roche/ADLM. The institution of Dr. Ramanan has received research support from American College of Radiology. Dr. Ramanan has received personal compensation in the range of $500-$4,999 for serving as a Conference Speaker/Organizer (Honoraria) with AANI. Dr. Ramanan has received personal compensation in the range of $500-$4,999 for serving as a Speaker/CME Content with Clinical Care Options.
Stuart J. McCarter, MD (Mayo Clinic)	The institution of Dr. McCarter has received research support from NIH. The institution of Dr. McCarter has received research support from American Academy of Sleep Medicine Foundation.
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic)	Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.
Prashanthi Vemuri, PhD (Mayo Clinic)	The institution of Dr. Vemuri has received research support from NIH.
Jonathan Graff-Radford, MD, FAAN	Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. Dr. Graff-Radford has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Graff-Radford has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Open evidence . The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Cognition therapeutics. Dr. Graff-Radford has received personal compensation in the range of $5,000-$9,999 for serving as a Faculty Member with IMPACT AD .

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