Neurology 2021 04 16;96(14):e1855-e1864. Epub 2021 Feb 16.
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 Research (L.M.S., J.Q.T.), and Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T., D.A.W.), Perelman School of Medicine at the University of Pennsylvania; and Michael J. Crescenz VA Medical Center (D.W., J.F.M., J.E.D.), Parkinson's Disease Research, Education, and Clinical Center, Philadelphia, PA.
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-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (t-tau) concentrations were measured. We used an autopsy-validated CSF cut point (t-tau:Aβ 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 ( = 4.80, = 0.03); both groups performed similarly on LF, RDS, and MMSE (all > 0.1). Clinically defined PDD and DLB groups did not differ in performance on any of these measures (all > 0.05). A correlation across all patients showed that BNT score was negatively associated with CSF t-tau (ρ = -0.28, < 0.05) and p-tau (ρ = -0.26, = 0.05) but not Aβ ( > 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.