Plasma neurofilament light (NFL) has been proposed as a blood-based biomarker for neurodegeneration in Alzheimer’s disease (AD) and parkinsonian disorders. However, the relationship between plasma NFL and cognitive decline in dementia due to Parkinson’s disease (PD) remains to be elucidated. In this research, 119 AD, 56 mild cognitive impairment (MCI), 26 non-demented PD (PDND), and 23 Parkinson’s disease dementia (PDD) patients, as well as 59 cognitively healthy controls (HC) were recruited. Each subject underwent a battery of neuropsychological testing. Plasma NFL levels were measured in duplicate using an NF-Light assay and transferred onto the Simoa platform with a home-brew kit. Plasma NFL was significantly increased in the AD group, compared with the control, MCI, PDND, and PDD groups. Plasma NFL was significantly higher in the PDD group, compared with the PDND group. High plasma NFL correlated with poor cognition in AD and PD, but not with motor symptoms in PD. Plasma NFL may represent a biomarker of cognitive decline in AD and PD, with more specificity for AD.

OBJECTIVES To investigate the summative effects of vascular risk factors (VRFs) on the progression of Alzheimer disease (AD). DESIGN Longitudinal follow‐up cohort study. SETTING AD patients from two teaching hospitals in Taiwan with 3‐year follow‐ups. PARTICIPANTS A total of 330 AD patients with a mean age of 80.7 years, a mean Mini‐Mental State Examination (MMSE) score 18.7, and a mean Clinical Dementia Rating Sum of Boxes (CDRSB) score of 6.9. MEASUREMENTS All patients completed a clinically functional assessment and a neuropsychological test battery at baseline and yearly follow‐ups. The VRF burden was combined into a summative VRF index at baseline (ie, having one, two, or more VRFs); VRFs included coronary heart disease, cardiac arrhythmia, hypertension, cerebrovascular disease, diabetes mellitus, obesity, smoking, and physical inactivity. The generalized estimating equation (GEE) method was used to analyze the correlations between the VRFs and longitudinal MMSE and CDRSB changes. RESULTS The results of the GEE adjusted for age, years of education, sex, disease duration, baseline MMSE score, time, apolipoprotein E (APOE) ε4 carrier status, use of medications (acetylcholinesterase inhibitors or N‐methyl‐D‐aspartate receptor antagonists), and hospitalization rates and showed that patients with more than three VRFs had more rapid cognitive decline than patients without VRFs (MMSE, P = .02; CDRSB, P = .001) as well as patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02). Subsequent analyses of APOE ε4 carriers with more than three VRFs also showed their more rapid cognitive decline compared with patients without VRFs (MMSE, P = .02; CDRSB, P = .001) and patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02), but no significant difference was found in APOE ε4 noncarriers. CONCLUSION Multiple VRFs have summative effects on the progression of AD, especially in APOE ε4 carriers. J Am Geriatr Soc 68:129–136, 2019