Cognitive Profile and Markers of AD-Type Pathology in Patients with Lewy Body Dementias

Objective: To determine whether Lewy body dementia (LBD) patients with likely Alzheimer’s disease-type (AD-type) co-pathology are more impaired on confrontation naming than those without likely AD-type co-pathology.

Methods: We selected 57 LBD patients (dementia with Lewy bodies, DLB, n=38; Parkinson’s disease dementia, PDD, n=19) with available AD CSF biomarkers and neuropsychological data. CSF beta-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 LBD with (LBD+AD, n=26) and without (LBD-AD, n=31) likely AD-type co-pathology. Analysis of co-variance (ANCOVA) 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), adjusting for age at dementia onset, time from dementia onset to test date, and time from CSF to test date. Spearman’s correlation related cognitive performance to CSF analytes.

Results: LBD+AD patients performed worse on BNT than LBD-AD patients (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 was negatively associated with CSF t-tau (rho= -0.28, p<0.05) and p-tau (rho=-0.26, p=0.05), but not Aβ42 (p>0.1).

Conclusion: Markers of AD-type co-pathology are implicated in impaired language performance in LBD. Biologically-based classification of LBD may be advantageous over clinically-defined syndromes to elucidate clinical heterogeneity.