CSF β-Amyloid 1-42 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease.
Low CSF β-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson's disease; data from a single cohort suggest β-amyloid 1-42 may be an early marker of cognitive impairment. Newly diagnosed Parkinson's participants (mean duration, 6.9 months) in the Parkinson's Progression Markers Initiative (n = 341) were assessed at baseline (untreated state) and followed for 2 years. CSF β-amyloid 1-42, α-synuclein, total tau, and tau phosphorylated at threonine 181 were collected at baseline. Participants were classified as having cognitive impairment (CI) if scores on two of six cognitive tests were 1.5 standard deviations below the standardized mean based on published norms in healthy controls. Multivariable regression analyses were used to determine the association between baseline CSF markers with cognitive impairment, defined by neuropsychological testing performance at 2-year follow-up. Fifty-five participants (16.1 %) had CI at baseline and were not included in further analyses. Thirty-seven of the 286 participants without CI at baseline (12.9 %) developed CI at 2 years. Participants with CI at 2 years had significantly lower mean baseline CSF β-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for α-synuclein, T-tau, or P-tau 181. In a regression model of 286 participants without baseline CI adjusted for age, gender, disease duration, education, motor severity, and depression status, lower baseline β-amyloid 1-42 levels were associated with higher odds of CI at 2 years. (OR(10pg/mL) = 1.04, 95 % CI 1.01-1.08, p < 0.05). CSF β-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson's disease.
Department of Neurology, Columbia University, 710 W 168th St, New York, NY, 10032, USA.
Mark
M
Terrelonge
Department of Neurology, Columbia University, 710 W 168th St, New York, NY, 10032, USA.
Karen S
KS
Marder
Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.
Daniel
D
Weintraub
Department of Neurology, Columbia University, 710 W 168th St, New York, NY, 10032, USA. RNA2104@COLUMBIA.EDU.
Roy N
RN
Alcalay
D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
CSF β-amyloid 1-42; Cognitive impairment; PPMI; Parkinson’s disease