β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies

. 2020 Dec 15 ; 95 (24) : e3257-e3268. [epub] 20200928

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, multicentrická studie, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid32989106

Grantová podpora
P50 AG016574 NIA NIH HHS - United States
R37 AG011378 NIA NIH HHS - United States
R01 AG041851 NIA NIH HHS - United States
C06 RR018898 NCRR NIH HHS - United States
R01 AG040042 NIA NIH HHS - United States
U01 AG006786 NIA NIH HHS - United States
U01 NS100620 NINDS NIH HHS - United States
R01 AG011378 NIA NIH HHS - United States
R01 NS080820 NINDS NIH HHS - United States

Odkazy

PubMed 32989106
PubMed Central PMC7836666
DOI 10.1212/wnl.0000000000010943
PII: WNL.0000000000010943
Knihovny.cz E-zdroje

OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid 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 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and 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 in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. 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 REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid 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, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.

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