Learning slopes in early-onset Alzheimer's disease

Dustin B Hammers¹, Sára Nemes¹, Taylor Diedrich¹, Ani Eloyan², Kala Kirby¹, Paul Aisen³, Joel Kramer⁴, Kelly Nudelman⁵, Tatiana Foroud⁵, Malia Rumbaugh⁵, Alireza Atri⁶, Gregory S Day⁷, Ranjan Duara⁸, Neill R Graff-Radford⁷, Lawrence S Honig⁹, David T Jones^{10

11}, Joseph C Masdeu¹², Mario F Mendez¹³, Erik Musiek¹⁴, Chiadi U Onyike¹⁵, Meghan Riddle¹⁶, Emily Rogalski¹⁷, Steve Salloway¹⁶, Sharon J Sha¹⁸, Raymond Scott Turner¹⁹, Sandra Weintraub¹⁷, Thomas S Wingo²⁰, David A Wolk²¹, Bonnie Wong²², Maria C Carrillo²³, Bradford C Dickerson²², Gil D Rabinovici⁴, Liana G Apostolova^{1

5

24}; LEADS Consortium

Affiliations

¹ Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
³ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
⁴ Department of Neurology, University of California, San Francisco, California, USA.
⁵ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁶ Banner Sun Health Research Institute, Sun City, Arizona, USA.
⁷ Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
⁹ Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
¹⁰ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹² Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
¹³ Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
¹⁴ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
¹⁵ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁶ Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
¹⁷ Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
¹⁸ Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
¹⁹ Department of Neurology, Georgetown University, Washington D.C., USA.
²⁰ Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
²¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²² Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²³ Medical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
²⁴ Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA.

PMID: 37243937
PMCID: PMC10806757
DOI: 10.1002/alz.13159

Learning slopes in early-onset Alzheimer's disease

Dustin B Hammers et al. Alzheimers Dement. 2023 Nov.

. 2023 Nov;19 Suppl 9(Suppl 9):S19-S28.

doi: 10.1002/alz.13159. Epub 2023 May 27.

Authors

Affiliations

¹ Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
³ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
⁴ Department of Neurology, University of California, San Francisco, California, USA.
⁵ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁶ Banner Sun Health Research Institute, Sun City, Arizona, USA.
⁷ Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
⁹ Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
¹⁰ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹² Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
¹³ Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
¹⁴ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
¹⁵ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁶ Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
¹⁷ Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
¹⁸ Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
¹⁹ Department of Neurology, Georgetown University, Washington D.C., USA.
²⁰ Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
²¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²² Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²³ Medical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
²⁴ Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA.

PMID: 37243937
PMCID: PMC10806757
DOI: 10.1002/alz.13159

Abstract

Objective: Investigation of learning slopes in early-onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early-onset dementia with and without β-amyloid positivity METHOD: Data from 310 participants in the Longitudinal Early-Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determined RESULTS: Worse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric-the learning ratio (LR)-outperformed other learning slope calculations across analyses CONCLUSIONS: Learning slopes appear to be sensitive to early-onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses.

Highlights: Learning is impaired in amyloid-positive EOAD, beyond cognitive severity scores alone. Amyloid-positive EOAD participants perform worse on learning slopes than amyloid-negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

Keywords: early-onset Alzheimer's disease; learning slopes; memory.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

No authors associated with this project have reported conflicts of interest that would impact these results. Author disclosures are available in the supporting information.

References

1. Alzheimer’s Association. 2021 Alzheimer’s disease facts and figures. Alzheimers Dementia. 2021;17:327–406. - PubMed
1. Zhu XC, Tan L, Wang HF, et al. Rate of early onset Alzheimer’s disease: a systematic review and meta-analysis. Ann Transl Med. 2015;3:38. - PMC - PubMed
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Learning slopes in early-onset Alzheimer's disease

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Learning slopes in early-onset Alzheimer's disease

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Conflict of interest statement

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