Confrontation Naming Deficit in Lewy Body Dementia Patients with Alzheimer’s Disease Co-Pathology (4234)

Objective: To test the association of confrontation naming performance in LBD patients with AD CSF biomarkers. Background: Lewy Body Dementias (LBD) are characterized by alpha-synuclein pathology but ~50% have sufficient Alzheimer’s disease (AD) co-pathology at autopsy for a second neuropathological diagnosis. These patients have worse overall prognosis, but little is known regarding the specific influence on cognition. LBD cognitive impairment is heterogeneous with core features of executive and visuospatial dysfunction; however, language difficulty is not uncommon and previous work suggests confrontation naming impairment may be associated with AD tau co-pathology. Design/Methods: We selected LBD patients (n=86) (PDD=36, DLB=50) with available CSF and neuropsychological data. AD CSF biomarkers were measured using the Luminex platform. We used an autopsy-validated cutpoint (Total-tau:Abeta42 ratio>0.3) to categorize patients as LBD with AD co-pathology (LBD+AD=33) and those without (LBD-AD=53). We used ANCOVA to test between-group comparisons on confrontation naming (30-item Boston Naming Test=BNT) and core features of executive (Letter Fluency=LF) and visuospatial (modified 6-item Judgment of Line Orientation=JOLO) functioning while adjusting for sex, disease duration, global cognition (MMSE) and clinical phenotype. Pearson correlation related testing to CSF analytes. Results: LBD+AD (mean=20.59, SD=6.31, n=22) performed worse on BNT than LBD-AD (mean=26.12, SD=3.85, n=32) (F=20.846, p 0.1). In contrast, both groups were similarly impaired on LF (LBD+AD mean=7.58, SD=6.31, n=19; LBD-AD mean=9.45, SD=5.19, n=31) (F=1.174, p>0.1) and JOLO (LBD+AD mean=3.07, SD=2.22, n=15; LBD-AD mean=4.08, SD=1.98, n=25) (F=2.414, p>0.1). We also found a moderate correlation between lower BNT score and increased CSF total-tau (r=−0.52, p Conclusions: These findings suggest that AD tau co-pathology has a specific influence on phenotypic expression of LBD in the language domain. BNT may be a useful clinical test to screen for likely mixed pathology, which has important prognostic implications. Disclosure: Dr. Howard has nothing to disclose. Dr. Cousins has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Nevler has nothing to disclose. Dr. Tropea has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genzyme, Medtronics.. Dr. Tropea has received research support from Sanofi.. Dr. Chen-Plotkin has nothing to disclose. Dr. Siderowf has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory board: Biogen, Axovant. Data and Safety Monitoring Board: Prilenia Therapeutics, Prevail Therapeutics, Wave Life Sciences.. Dr. Siderowf has received research support from Site investigator: Voyager Therapeutics, Denali Therapeutics.. Dr. Weintraub has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honoraria for consultancy from Acadia, Alkahest, CHDI Foundation, Clintrex LLS, F. Hoffmann-LaRoche Ltd and Sunovion. Dr. Weintraub has received royalty, license fees, or contractual rights payments from University of Pennsylvania for the QUIP and QUIP-RS.Dr. Shaw has nothing to disclose. Dr. Trojanowski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Johnson a Johnson. Dr. Grossman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GE Whitney, Ionis, and Alector. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. Grossman has received research support from Biogen and Avid. Dr. Irwin has nothing to disclose.