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Cognitive Profile and Markers of Alzheimer Disease–Type Pathology in Patients With Lewy Body Dementias
Open accessAbstract
Objective To determine whether patients with Lewy body dementia (LBD) with likely Alzheimer disease (AD)–type copathology are more impaired on confrontation naming than those without likely AD-type copathology. Methods We selected 57 patients with LBD (dementia with Lewy bodies [DLB], n = 38; Parkinson disease dementia [PDD], n = 19) with available AD CSF biomarkers and neuropsychological data. CSF β-amyloid1-42 (Aβ42), phosphorylated-tau (p-tau), and total-tau (t-tau) concentrations were measured. We used an autopsy-validated CSF cut point (t-tau:Aβ42 ratio > 0.3, n = 43), or autopsy data when available (n = 14), to categorize patients as having LBD with (LBD + AD, n = 26) and without (LBD − AD, n = 31) likely AD-type copathology. Analysis of covariance tested between-group comparisons across biologically defined groups (LBD + AD, LBD − AD) and clinical phenotypes (DLB, PDD) on confrontation naming (30-item Boston Naming Test [BNT]), executive abilities (letter fluency [LF], reverse digit span [RDS]), and global cognition (Mini-Mental State Examination [MMSE]), with adjustment for age at dementia onset, time from dementia onset to test date, and time from CSF to test date. Spearman correlation related cognitive performance to CSF analytes. Results Patients with LBD + AD performed worse on BNT than patients with LBD − AD (F = 4.80, p = 0.03); both groups performed similarly on LF, RDS, and MMSE (all p > 0.1). Clinically defined PDD and DLB groups did not differ in performance on any of these measures (all p > 0.05). A correlation across all patients showed that BNT score was negatively associated with CSF t-tau (ρ = −0.28, p < 0.05) and p-tau (ρ = −0.26, p = 0.05) but not Aβ42 (p > 0.1). Conclusion Markers of AD-type copathology are implicated in impaired language performance in LBD. Biologically based classification of LBD may be advantageous over clinically defined syndromes to elucidate clinical heterogeneity.
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“Indeed, in another study, we found impaired naming in people presenting with synucleinopathies who had concomitant ADNC and this was directly associated with a high p‐tau level in their CSF. 54”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [54]
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Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease
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Metadata
- Authors
- Howard, E., Irwin, D. J., Rascovsky, K., Nevler, N., Shellikeri, S., Tropea, T. F., Spindler, M., Deik, A., Chen-Plotkin, A., Siderowf, A., Dahodwala, N., Weintraub, D., Shaw, L. M., Trojanowski, J. Q., Vaishnavi, S. N., Wolk, D. A., Mechanic-Hamilton, D., Morley, J. F., Duda, J. E., Grossman, M., & Cousins, K. A. Q.
- Affiliations
- Philadelphia VA Medical Center (US)
- From the Department of Neurology (E.H., D.J.I., K.R., N.N., S.S., T.F.T., M.S., A.D., A.C.-P., A.S., N.D., D.W., S.N.V., D.A.W., D.M.-H., J.F.M., J.E.D., M.G., K.A.Q.C.), Frontotemporal Degeneration Center (E.H., D.J.I., K.R., N.N., S.S., M.G., K.A.Q.C.), Parkinson’s Disease and Movement Disorders Center (T.F.T., M.S., A.D., A.C.-P., A.S., N.D., D.W.), Digital Neuropathology Laboratory (D.J.I.), Alzheimer’s Disease Center (J.Q.T., S.N.V., D.A.W., D.M.-H.), Center for Neurodegenerative Disease...
- ORCID
- Howard, Erica
- Irwin, David J.
- Nevler, Naomi
- Shellikeri, Sanjana
- Tropea, Thomas F.
- Spindler, Meredith
- Deik, Andres
- Siderowf, Andrew
- Dahodwala, Nabila
- Weintraub, Daniel
- Shaw, Leslie M.
- Trojanowski, John Q.
- Vaishnavi, Sanjeev N.
- Wolk, David A.
- Mechanic-Hamilton, Dawn
- Morley, James F.
- Duda, John E.
- Grossman, Murray
- Cousins, Katheryn A.Q.
- Venue
- Neurology
- Published
- 2021-04-06
- Volume
- 96
- Issue
- 14
- Pages
- e1855-e1864
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC8105963
- OpenAlex
- W3131805017
- Cited by
- 47
- References
- 56
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 9
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (K23AG065499, U19AG062418, P01AG066597, P30AG010124, P01AG017586, U01AG052943, P01AG019724, U19AG024904, R01AG054519, P30AG072979)
- National Institute of Neurological Disorders and Stroke (K23NS114167, P50NS053488)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- dementia with Lewy bodies, Parkinson's disease dementia, confrontation naming, Boston Naming Test, cerebrospinal fluid biomarkers, tau protein, phosphorylated tau, amyloid-beta 42, language impairment, executive function, cognitive profile, clinical heterogeneity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Language Tests, Male, Middle Aged, Biomarkers, Amyloid beta-Protein Precursor, tau Proteins, Lewy Body Disease
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