Cognitive Profile and Markers of Alzheimer Disease-Type Pathology in Patients With Lewy Body Dementias

Neurology. 2021 Apr 6;96(14):e1855-e1864. doi: 10.1212/WNL.0000000000011699. Epub 2021 Feb 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology*
  • Female
  • Humans
  • Language Tests
  • Lewy Body Disease / cerebrospinal fluid*
  • Lewy Body Disease / pathology*
  • Male
  • Middle Aged
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Protein Precursor
  • Biomarkers
  • tau Proteins