Specific Nutritional Biomarker Profiles in Mild Cognitive Impairment and Subjective Cognitive Decline Are Associated With Clinical Progression: The NUDAD Project

Abstract

Objectives: Nutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Design, setting and participants: We included 299 patients without dementia (n ¼ 149 SCD; age 61 AE 10 years, female 44%, n ¼ 150 MCI; age 66 AE 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years. Methods: We measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction Funding sources: The NUDAD project is funded by NWO-FCB (project number 057-14-004), and Francisca de Leeuw and Maartje Kester are appointed on this project. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Docosahexaenoic acid and total omega-3 fatty acids measurements were funded by Biobanking and Biomolecular Resource Research Infrastructure (BBMRI)-NL (NWO 184.021.007). Theobromine measurements were supported by Fundação para a Ciência e a Tecnologia (FCT) [

LDL cholesterol and uridine levels in blood are potential nutritional biomarkers for clinical progression in Alzheimer's disease: The NUDAD project

“…Additionally, in a combined analysis of predementia stages in our prospective and retrospective cohort, higher HDL cholesterol levels and lower CSF SAM and SAH levels in MCI were associated with clinical progression. The role of HDL cholesterol levels in AD is inconclusive 17,38 . One explanation for our findings could be that HDL is dysfunctional in AD, as also reported for type 2 diabetes and coronary heart disease, resulting in impaired protective effects while HDL cholesterol levels remain normal 39 .…”

“…A previous cross‐sectional study showed that lower levels of several nutritional biomarkers are already prevalent in patients with MCI 16 . In addition, in a retrospective study of patients with subjective cognitive decline (SCD) and MCI, we found modest associations between higher levels of high‐density lipoprotein (HDL) cholesterol and lower levels of CSF S‐adenosylmethionine (SAM) and clinical progression 17 . The role of nutritional biomarkers across the complete cognitive spectrum of AD remains, however, largely unknown.…”

“…Subsequently, we repeated the models (1) stratified for baseline diagnosis, (2) in amyloid‐positive patients only, and (3) stratified for lipid‐lowering medication (yes/no). Last, we focused our analysis on predementia stages, combining individual patient data from the current cohort and from the previously published, retrospective cohort 17 . Eight patients were included in both cohorts, and were therefore excluded from the retrospective cohort.…”

Cerebrospinal fluid oxidative stress markers in Alzheimer's disease

“…S‐adenosylmethionine (SAM), a natural compound produced in homocysteine metabolism in the human body, is the primary methyl donor and the precursor of glutathione. In mild cognitive impairment (MCI) with putative early AD pathology, SAM in the CSF was decreased 43,44 . SAM level is decreased in the brain of AD patients 45 …”

Near-moderate cognitive decline

“…В ранее упомянутом исследовании 45 and Up Study [26] была выявлена ассоциация между СКС и гиперхолестеринемией. В другой работе [54] высокий уровень липопротеинов высокой плотности был связан с прогрессированием СКС.…”