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Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.
Hoscheidt, S, Sanderlin, AH, Baker, LD, Jung, Y, Lockhart, S, Kellar, D, Whitlow, CT, Hanson, AJ, Friedman, S, Register, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;18(3):457-468
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Plain language summary
There is a current understanding that Alzheimer’s disease (AD) development is related to a high intake of saturated fat and simple carbohydrates, which are found in abundance in the so-called Western Diet (WD). In contrast the consumption of low saturated fat and simple carbohydrates characteristic of the Mediterranean Diet (MD), has been associated with a reduced risk for the development of AD. This study aimed to look at the association of the MD and WD with AD in a more robust way using the randomised control method in 84 individuals both with and without mild memory impairment. The results showed that depending on whether an individual has mild brain impairment determines their response to the MD or WD after 4 weeks. In those without brain impairment the adoption of the WD resulted in a shift towards increasing the risk for AD development and the reverse following the MD. Whereas in those with brain impairment, the adoption of the WD was protective against the development of AD and the MD moved individuals towards worse disease outcomes. It was concluded that diet can be of importance in the prevention or progression of AD and that further studies are required to determine the possible mechanisms through which these two diets can act differentially. This study could be used by health care professionals to understand that diet can have a large impact on AD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- A Med-diet may be beneficial for supporting brain health, cognitive function. metabolic health and reduce the risk of an AD pathology in middle-aged adults with normal cognitive function
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Epidemiological studies have associated a Western diet (West-diet) with an increased risk of Alzheimer’s disease (AD) and other dementias. This study aimed to examine the impact of a Mediterranean-diet (Med-diet) versus a West-diet on AD pathology, cognition, vascular function and metabolic markers in middle aged adults with normal cognitive (NC) function compared to adults with mild cognitive impairment (MCI).
Methods
N=41 NC adult females completed the Med-diet and N=43 adult females with MCI completed the West-diet arm of this study. The average age of the participants was 56y. All participants received isocaloric diets which were either high or low in saturated fat, sodium and glycaemic index (GI) for 4 weeks. Statistical analyses were conducted per dietary arm as well as per cognitive function (NC vs MCI).
Results
- NC Participants were found to have decreased cerebro-spinal fluid (CSF) biomarkers (p=.026) following the Med-diet and increased levels following the West-diet. Whereas, cerebral perfusion increased following the med-diet and decreased after the West-diet (p=.003). These results indicate a reduced AD risk. The MCI group showed no changes to CSF or cerebral perfusion for either dietary group.
- Cognition tended to improve for the NC Med-diet and remain the same for the NC West-diet group. No changes were found for the MCI groups.
- Total cholesterol levels were increased following the West-diet and decreased following the Med-diet for both groups (p=0.0001).
- Glucose and HbA1C were unchanged in the NC group following the Med-diet, increased for the West-diet (p=.049) and decreased for the MCI group (p=<.001). whereas fasting insulin was increased in the NC Med-diet group and decreased in the MCI Med-diet (p=.0.12) and West diet groups.
Conclusion
The results of this study found that diet may modulate AD pathology, cognitive and metabolic function in middle-aged adults. A West-like diet may increase risk of AD through its effects on impairing cognitive function, reducing cerebral infusion and negatively influencing metabolic health in NC adults. Conversely, A Med-diet may promote brain function and metabolic health. However, surprisingly, in this study the results were reversed for MCI middle aged adults, the results showed improvement in metabolic and cerebrospinal fluid biomarkers for the West-diet. These results require further confirmation.
No conflicts of interest were declared.
Clinical practice applications:
- A Med-diet may be beneficial for supporting brain health, cognitive function, metabolic health and reducing the risk of an AD pathology in middle-aged adults with normal cognitive function but not for those with MCI.
Considerations for future research:
The authors acknowledged several limitations to this study.
- These results require further confirmation through longer and larger studies, particularly the surprising finding that a West-diet may confer beneficial effects on metabolic and brain health for middle-aged adults with MCI.
Abstract
INTRODUCTION Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. METHODS Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. RESULTS CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion. DISCUSSION Diet response during middle age may highlight early pathophysiological processes that increase AD risk.
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The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.
Brakedal, B, Dölle, C, Riemer, F, Ma, Y, Nido, GS, Skeie, GO, Craven, AR, Schwarzlmüller, T, Brekke, N, Diab, J, et al
Cell metabolism. 2022;34(3):396-407.e6
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Parkinson’s disease (PD) is a major cause of death and disability, and current treatments can provide partial symptomatic relief, mainly for motor symptoms but make no substantial impact on disease progression. A growing body of evidence supports that boosting cellular levels of nicotinamide adenine dinucleotide (NAD) may confer neuroprotective effects in both healthy aging and neurodegeneration. The primary aim of this study was to assess penetration and metabolic responses of the brain to nicotinamide riboside (NR) supplementation in patients with PD. This study is a double-blinded, randomised, placebo-controlled phase I study of NR in newly diagnosed PD patients, naïve to dopaminergic therapy. Participants (n=30) where randomly assigned (1:1) to one of the two groups: NR group or placebo group. Results show that: - oral NR therapy increases brain NAD levels and impacts cerebral metabolism in PD. - supplementation with NR may target multiple processes implicated in the pathophysiology of the disease by upregulating the expression of genes involved in mitochondrial respiration, oxidative damage response, lysosomal and proteasomal function and downregulating inflammatory cytokines in the central nervous system. Authors conclude that NR can be a potential neuroprotective agent against PD. However, further investigation in a larger trial is required to warrant these findings.
Abstract
We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.