LDL cholesterol and uridine levels in blood are potential nutritional biomarkers of AD progression: The NUDAD project: Biomarkers (non‐neuroimaging) / Novel biomarkers. (7th December 2020)

• Record Type: Journal Article
• Authors: de Leeuw, Francisca A.; Tijms, Betty M.; Doorduijn, Astrid S; Hendriksen, Heleen M.A.; van de Rest, Ondine; de van der Schueren, Marian; Visser, Marjolein; van den Heuvel, Ellen G.H.M.; van Wijk, Nick; Bierau, Jörgen; Scheltens, Philip; Kester, Maartje I.; van Der Flier, Wiesje; Teunissen, Charlotte E.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.043108
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Suboptimal nutritional status is considered a modifiable risk factor for Alzheimer's disease (AD). Identification of nutritional biomarker levels that are related to clinical progression might provide targets for dietary intervention studies. Therefore, we examined associations between nutritional biomarkers and clinical progression in a prospective study with individuals with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and AD‐type dementia. Method: We included 551 participants: 219 patients with SCD (age 61±8y, F47%), 135 patients with MCI (age 66±8 y, F40%) and 197 patients with AD (age 67±8y, F50%). Mean follow‐up was 2±1 years. Main outcome was time to clinical event operationalized as presence of at least one of the following: 1) in SCD, progression to MCI or dementia; in MCI, progression to dementia; in AD an increase of ≥1 point on clinical dementia rating scale; or 2) admission to a nursing home or deceased; or 3) self‐reported progression of cognitive symptoms. Baseline levels of cholesterol, triglycerides, glucose, homocysteine, folate, vitamin A, B12, E, and uridine were measured in blood and those of S‐adenosylmethionine and S‐adenosylhomocysteine in cerebrospinal fluid. Cox proportional hazard models adjusted for sex, age, diagnosis, BMI and lipid lowering medication were used to assess associations of baseline nutritional biomarker levels with time to clinical progression, in the total cohort and stratified for baseline diagnosis (SCD/MCI/AD). We repeated analyses in the total cohort restricted to amyloid positive patients. Result: Clinical progression was observed in 25 (11%) patients with SCD, 45 (33%) with MCI and 100 (51%) with AD. None of the nutritional biomarkers was associated with clinical progression in the total cohort. Higher levels of LDL cholesterol in SCD (HR (95%CI) 1.92 (1.05‐3.52)), and lower uridine levels in AD were associated with clinical progression (HR (95%CI) 0.78 (0.62‐0.99)) (Table 1). In amyloid positive patients, lower uridine levels were associated with clinical progression. Conclusion: In this large prospective memory‐clinic study, we found that higher LDL cholesterol and lower uridine levels were associated with clinical progression in SCD and AD dementia respectively. Our findings suggest that nutritional interventions should take into account clinical stage, and target uridine and cholesterol levels.