Distinguishing Prodromal Dementia With Lewy Bodies From Prodromal Alzheimer Disease: A Longitudinal Study.

Background and Objectives: It can be clinically challenging to differentiate dementia with Lewy bodies (DLB) and Alzheimer disease (AD). As potential therapies emerge with the goal of slowing or halting misfolded protein aggregation, it is imperative to be able to identify individuals before the disease becomes disabling. Differentiating between DLB and AD in the preclinical or prodromal phase of DLB and AD becomes more important. Studies are needed to validate the proposed criteria for prodromal DLB.
Methods: Longitudinal data were obtained from the Uniform Data Set of the National Alzheimer's Coordinating Center. Included participants had a baseline diagnosis of normal or mild cognitive impairment and a consecutive 2-year follow-up diagnosis of DLB or AD. We examined whether core DLB clinical features, supportive neuropsychiatric features, and neuropsychological data in the 2 years preceding the dementia diagnosis distinguished DLB from AD.
Results: We identified 143 participants with DLB and 429 age-matched/sex-matched participants with AD. The presence of 2 or more core DLB features in the year before dementia diagnosis yielded the greatest AUC (0.793; 95% CI 0.748-0.839) in distinguishing prodromal DLB from prodromal AD. Sleep disturbances, hallucinations, and a cognitive profile of worse processing speed, attention, and visuoconstruction performance were evident at least 2 years before the dementia diagnosis in DLB compared with AD.
Discussion: Data from this multisite, longitudinal, well-characterized research North American cohort support the validity of the recently published criteria for prodromal DLB. In the prodromal stage, patients who subsequently develop DLB are more likely to have core DLB clinical features and worse attention, processing speed, and visuospatial performance than those who go on to develop AD. Differentiation of DLB and AD before dementia emerges provides an opportunity for early, disease-specific intervention and overall management.
Competing Interests: K.A. Wyman-Chick receives research support from the NIH (R21AG074368). T.J. Ferman receives support from the National Institutes of Health and from Mangurian Foundation Lewy Body Dementia Program at Mayo Clinic. M.J. Armstrong receives research support from the NIH (R01AG068128, P30AG066506, R01NS121099, and R44AG062072), the Florida Department of Health (grants 20A08, 24A14, and 24A15), and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. She serves on the DSMBs for the Alzheimer's Therapeutic Research Institute/Alzheimer's Clinical Trial Consortium and the Alzheimer's Disease Cooperative Study. She has provided educational content for Medscape, Vindico CME, and Prime Inc. E. Bayram receives research support from the NIH (K99AG073453) and the Lewy Body Dementia Association. B.F. Boeve has served as an investigator for clinical trials sponsored by Alector, Biogen, and Transposon. He serves on the Scientific Advisory Board of the Tau Consortium, which is funded by the Rainwater Charitable Foundation. He receives support from NIH, the Mayo Clinic Dorothy, Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Foundation. D. Weintraub has received research funding or support from MJFF, Alzheimer's Therapeutic Research Initiative, Alzheimer's Disease Cooperative Study, the International Parkinson and Movement Disorder Society, and National Institute on Aging (NIA); honoraria for consultancy from Acadia, Aptinyx, Biogen, CHDI Foundation, Clintrex LLC, Eisai, Enterin, F. Hoffmann-La Roche Ltd, Ferring, Janssen, Otsuka, Promentis, Sage, Signant Health, Sunovion, and Takeda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. M.J. Barrett receives research support from the NIH (R21AG077469). Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
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