TABLE 6.

Summary of findings from the GRADE assessment

Neurodegenerative disease	Outcome	Effect	Number of participants (studies)	Certainty in the evidence
Alzheimer's disease	Improvement in cognition	Most studies (3/5) showed no statistically significant effects of treatment	634 (5 randomized controlled trials)	LOW1 certainty ⊕⊕OO
Mild cognitive impairment	Improvement in cognition	Studies which examined cognition showed small-medium improvements or no effect	130 (6 randomized controlled trials)	VERY LOW2,3 certainty ⊕OOO
Parkinson's disease or MCI secondary to Parkinson's disease	Improvement in cognition and motor function	Both studies showed mixed results for measures of cognition and motor function	61 (2 randomized controlled trials)	VERY LOW4,5 certainty ⊕OOO
Multiple sclerosis	Improvement in quality of life and disability	Most studies (3/5) showed no significant effect of treatment	154 (3 randomized controlled trials; 1 nonrandomized prospective study)	VERY LOW6,7 certainty ⊕OOO

¹Serious inconsistencies were observed across the evidence significantly lowering the certainty of the body of evidence. Therefore, we chose to downgrade certainty by 2 levels.

²Very serious risk of bias across studies because of unclear or inadequate blinding, sequence generation, and allocation concealment.

³Serious imprecision and inconsistency were considered together as there were small effects or “no effects” reported in studies.

Note. Indirectness was not downgraded because the physiological endpoints were comparable between studies despite differing interventions (dietary compared with exogenous ketogenic therapies).

⁴Very serious risk of bias across studies because of unclear sequence generation and lack of blinding.

⁵The evidence was rated to be of very low certainty due to serious or very serious concerns across 4/5 categories.

⁶Very serious risk of bias across studies because of unclear sequence generation and lack of blinding.

⁷The evidence was rated to be of very low certainty due to serious or very serious concerns across 4/5 categories.

Certainty of evidence key = VERY LOW, ⊕OOO; LOW, ⊕⊕OO; MODERATE, ⊕⊕⊕O; HIGH, ⊕⊕⊕⊕.

GRADE, Grading of Recommendations, Assessment, Development and Evaluation; MCI, mild cognitive impairment.