Key Messages

• In older adults with CATD, evidence for the nutritional drink Souvenaid^® compared with placebo showed:

  • No difference for function, serious adverse events, or withdrawals due to adverse events (low strength of evidence [SOE]).
  • Insufficient evidence to draw conclusions for cognition, quality of life, staging, or clinical impression of change.

Baseline Study Characteristics

Three publications reporting two trials (n=786) examined the efficacy of Souvenaid^®, a nutritional drink consisting of omega-3 fatty acids, phospholipids, vitamins (B12, B6, C, and E), folate, and selenium. ^315–317 One trial enrolled community-dwelling subjects with mild clinical Alzheimer’s-type dementia (CATD) (Mini-Mental State Exam [MMSE] ≥20). ^{315, 316} One trial enrolled participants’ with mild to moderate CATD severity (MMSE 14 to 24). ³¹⁷ Participant mean age was 76 years, 49 percent of participants were male, and race was not reported. Treatment duration for both trials was 24 weeks.

Outcomes

Table 7.1 summarizes primary efficacy and harms results. For efficacy, Souvenaid^® and placebo did not differ for change in function (low SOE) and evidence was insufficient to draw conclusions about differences in brief multidomain cognitive batteries and staging. No studies reported data on brief cognitive tests commonly used as individual stand-alone tests, domain level cognitive tests, quality of life, clinical impression of change, or change in patient residence to a different level of independence.

For harms, risk of serious adverse events and withdrawals due to adverse events did not differ between Souvenaid^® and placebo (both low SOE). In one trial reporting, confusion was reported in one placebo group participant and incident falls was reported in one participant each in the Souvenaid^® and placebo groups. ^{315, 316} No trial reported data on somnolence, extrapyramidal symptoms, stroke or mortality.

Table 7.1

Summary of findings for primary outcomes: Souvenaid^® versus placebo.

Key Messages

• In older adults with CATD, evidence for omega-3 fatty acids compared with placebo showed:

  • No difference for cognition (low SOE).
  • Insufficient evidence to draw conclusions about function, quality of life, staging, clinical impression of change, serious adverse events, or withdrawals due to adverse events.

Baseline Study Characteristics

Three publications reporting two trials (n=230) examined the efficacy of omega-3 fatty acids on cognition, function, and quality of life in patients with CATD.^318–320 Both trials were medium ROB. Mean age across both study populations was 74 years, and approximately 47 percent of participants were male. Neither trial reported race. Treatment duration was 6 months for one trial and 12 months for the other trial. The trials enrolled participants with mild to moderate CATD, with a mean MMSE score of 23 across both studies (MMSE 15 to 26). Participants were community dwelling. One trial used capsules with docosahexaenoic acid (430 mg) and eicosapentaenoic acid (150 mg).^{318, 319} The other trial used capsules of fish oil concentrate with docosahexaenoic acid (675 mg) and eicosapentaenoic acid (975 mg).³²⁰

Outcomes

Table 7.2 summarizes primary efficacy and harms results. For efficacy, omega-3 fatty acids and placebo did not differ for cognition, but evidence was insufficient to draw conclusions about differences for function or staging. No studies reported data on domain-level cognitive tests, quality of life, clinical impression of change or change in patient residence to a different level of independence.

For harms, evidence was insufficient to draw conclusions about differences between omega-3 fatty acids and placebo for risk of serious adverse events³²⁰ and withdrawals due to adverse events. ^{318, 319} One study reported one participant with an incident fall and no deaths in the omega-3 fatty acid group and reported two with a fall and one death in the placebo group. ³²⁰ No studies reported data on somnolence, confusion, extrapyramidal symptoms or stroke.

Table 7.2

Summary of findings for primary outcomes: omega-3 fatty acids versus placebo.

Key Messages

• Evidence was insufficient to draw conclusions about the efficacy and harms of the following supplements, for which all eligible trials were medium ROB, and results were analyzed:

  • Omega-3 fatty acids combined with alpha lipoic acid, antioxidants, choline alfoscerate, prolonged release melatonin, sodium selenite, soy isoflavones, copper, and folic acid combined with vitamin B (each supplement was studied in 1 trial only).
• Evidence was insufficient to draw conclusions about the efficacy and harms of the following supplements, for which all eligible trials were rated high ROB, and results were not analyzed:

  • Ginkgo biloba (6 trials), acetyl-l-carnitine (5 trials), ginseng (3 trials), curcumin (2 trials), lecithin (2 trials), vitamin E (2 trials), coconut oil (1 trial), folic acid (1 trial), multivitamin (1 trial), oral nicotinamide adenine dinucleotide (1 trial), ninjin’yoeito (1 trial), Colostrinin® (1 trial), selenium (1 trial), thiamine (1 trial), and resveratrol (1 trial).
• No eligible studies were identified that examined the efficacy or harms of Prevagen (apoaequorin), phosphotidylserine or Huperzine.

Baseline Study Characteristics

Eight publications reporting eight trials examined the efficacy of omega-3 fatty acids combined with alpha lipoic acid,³²⁰ antioxidants,³²¹ choline alfoscerate,³²² prolonged release melatonin,³²³ sodium selenite,³²⁴ soy isoflavones,³²⁵ copper,³²⁶ and folic acid combined with vitamin B,³¹⁴ respectively. All trials were medium ROB. Six studies enrolled subjects with mild and/or moderate CATD,^320–324 while two did not specify the severity of enrolled subjects.^{325, 326}

Primary Outcomes

Though collectively these eight trials reported a few statistically significant results favoring individual supplements compared with placebo, evidence was insufficient to draw conclusions about differences between each of these supplements compared with placebo for all reported efficacy and harms outcomes.

For a trial that compared omega-3 fatty acids plus alpha lipoic acid versus placebo (n=26), results statistically favored the supplement combination on an IADL function measure, but not for cognition or an ADL function measure.³²⁰ For a trial of add-on prolonged release melatonin compared with add-on placebo in participants who continued cholinesterase inhibitor treatment (n=80), results statistically favored the add-on melatonin group for change in cognition (MMSE, ADAS-Cog) and function (IADL).³²³ In a trial that compared choline alfoscerate with placebo (n=261), results statistically favored choline alfoscerate for cognition (MMSE, ADAS-Cog), global staging (Global Deterioration Scale [GDS]), and clinical impression of change (Clinical Global Impression [CGI]).³²²

By comparison, individual trials on antioxidant supplementation (n=52), sodium selenate (n=40), soy isoflavones (n=65), add-on copper (n=68), and folic acid combined with vitamin B (n=409) reported no difference between the supplement and placebo for all measured domains.^{314, 321, 324–326} Trials reported limited information about harms. Appendix Tables F.10-F.43 provide detailed evidence tables and strength of evidence for key comparisons and outcomes.