Abstract
OBJECTIVE: In a multi-center cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that amyloid-β and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 DLB patients (45-93 years, 31% women).
Positivity on amyloid-β (A+) and tau (T+) biomarkers was determined by cerebrospinal fluid amyloid-β 1-42 and phosphorylated tau in the European cohort, and Pittsburgh compound-B and AV-1451 positron emission tomography in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, A+T+.
RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age and A+ and T+ increased with age both in women and men.
A+ increased more in APOE ε4 carriers with age than in non-carriers. A+ was the main predictor of lower cognitive performance when considered together with T+.
T+ was associated with a lower frequency of parkinsonism and probable rapid eye movement sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype.
CONCLUSIONS: Alzheimer's disease pathologic changes are common in DLB and are associated with the clinical phenotype. Amyloid-β is associated with cognitive impairment and tau pathology is associated with lower frequency of clinical features of DLB.
These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, amyloid-β is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.