Article - Effects of ketogenic diet on cognitive function of patients with Alzheimer's disease: a systematic review and meta-analysis.

Plain Language Summary

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline and memory loss. Recent interest has focused on dietary interventions, such as the ketogenic diet (KD), which may offer neuroprotective benefits by altering brain metabolism and reducing inflammation. The primary aim of this study was to evaluate the effects of the ketogenic diet on cognitive function in patients with AD. This study was a systematic review and meta-analysis of ten clinical trials. Results showed significant improvements in cognitive function in patients following a ketogenic diet, as measured by various cognitive assessment scales. Furthermore, patients on the ketogenic diet reported better quality of life scores compared to those on standard diets. Authors concluded that the ketogenic diet may have a positive impact on cognitive function and quality of life in patients with AD. These results support further research to confirm the potential therapeutic benefits of the ketogenic diet for AD patients.

Expert Review

Reviewer: Karin Elgar

13th Nov 2024

Conflict of interest

None

Take home message

A KD may support cognitive function and mental state in patients with AD but may also have a negative effect on blood lipids.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The aim of this review was to evaluate the potential benefits of a ketogenic diet (KD) for cognitive function in patients with Alzheimer’s disease (AD).

Methods

Systematic review and meta-analysis, searching PubMed, Cochrane Library, and Embase.
Registered on PROSPERO and adhering to PRISMA Guidelines.
Inclusion criteria: Randomised controlled trials (RCTs), patients with AD (other types of dementia were excluded) and studies using the following outcome measures -Mini mental status examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), daily living activities (ADL), and the Nishimura Geriatric Rating Scale for Mental Status (NM).
Cochrane Risk of Bias tool was used to assess study quality.

Results

10 RCTs with a total of 691 AD patients were included. Duration of intervention ranged from 12-60 weeks.
None of the studies had an overall high risk of bias.
Improvements were seen in MMSE (p=0.003, n=5), ADAS-cog (p=0.002, n=3) and NM (p=0.003, n=2) but not in ADL (p=0.95, n=2).
4 of the studies evaluated blood lipids and meta-analysis showed an increase in triglycerides (p=0.02) and LDL-cholesterol (p=0.03), with no change in total or HDL cholesterol (p=0.09 and p=0.63, respectively).

Conclusion

The authors conclude that there is “compelling evidence” for the potential of a KD in patients with AD whilst also highlighting the potential negative effects on blood lipids.

Clinical practice applications

A ketogenic diet could be considered to support cognitive function and mental state in patients with AD.
When advising on a ketogenic diet, blood chemistry, including blood lipids, should be monitored.
The impacts of long-term KD use in relation to the gut microbiome and dietary compliance should be considered when recommending KD as a dietary strategy for AD.

Considerations for future research

Research to determine the optimal type of ketogenic diet/diet composition to support cognitive function.
Clinical trials of a KD in other types of dementia.

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Abstract

BACKGROUND

Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment of Alzheimer's disease (AD). But the clinical effect of treating AD is uncertain.

OBJECTIVE

To systematically review the impact of KD on cognitive function in AD.

METHODS

We conducted a search of three international databases-PubMed, Cochrane Library, and Embase-to retrieve RCTs on the KD intervention for AD from the inception of the databases through October 2023. Two reviewers searched and screened the literature, extracted and checked relevant data independently, and assessed the risk of bias of the included studies. The meta-analysis was carried out utilizing RevMan 5.3 software.

RESULTS

A total of 10 RCTS involving 691 patients with AD were included. There were 357 participants in the intervention group and 334 participants in the control group. The duration of the KD intervention ranged from a minimum of 3 months to a maximum of 15 months. Meta-analysis results showed that KD could effectively improve the mental state of the elderly (NM scale) [MD = 7.56, 95%CI (3.02, 12.10), P = 0.001], MMSE [MD = 1.25, 95%CI (0.46, 2.04), P = 0.002], and ADAS-Cog [MD = -3.43, 95%CI (-5.98, -0.88), P = 0.008]. The elevation of ketone body (β-hydroxybutyric) [MD = 118.84, 95%CI (15.20, 222.48), P = 0.02] may also lead to the elevation of triglyceride [MD = 0.19, 95%CI (0.03, 0.35), P = 0.02] and low density lipoprotein [MD = 0.31, 95%CI (0.04, 0.58), P = 0.02].

CONCLUSION

Research conducted has indicated that the KD can enhance the mental state and cognitive function of those with AD, albeit potentially leading to an elevation in blood lipid levels. In summary, the good intervention effect and safety of KD are worthy of promotion and application in clinical treatment of AD.