Table 1. Results of a retrospective review of dietary supplement that has a beneficial role in various cognitive domains in patients' with Alzheimer's disease.

ADAS-Cog - Alzheimer’s Disease Assessment Scale-Cognitive Subscale, ADCS-ADL - Alzheimer’s Disease Cooperative Study-Activities of Daily Living Subscale, ADL - Activities of Daily Living, BPI - Brief Pain Inventory, BPSD - Behavioral and Psychological Symptoms of Dementia, CERAD - Consortium to Establish a Registry for Alzheimer’s Disease, CDR-SB - Clinical Dementia Rating Scale-Sum of Boxes, DAD - Disability Assessment in Dementia, DRS-2 - Dementia Rating Scale, FFQ - Food Frequency Questionnaire, GDS - Geriatric Depression Scale, MMSE - Mini-Mental State Examination, NPI - Neuropsychiatric Inventory, NTB - Neuropsychological Test Battery, PLI - Phase Lag Index, WMS - Wechsler Memory Scale, WMS-R - Wechsler Memory Scale-Revised, WMS-RLM - Wechsler Memory Scale-Revised Logical Memory

Study	No	Supplement	Markers and outcomes	Domains improved
1. Moré MI et al. [22]	Study 1: n= 72 (60-80) years. Study 2: n= 96 (50-90) years.	Phosphatidylserine (PS) and Phosphatidic acid (PA)	Study 1: At 3 months - WMS. Study 2: At 2 months - General self-reporting, scoring of ADL are assessed.	Study 1: Positive influence on memory and mood in pre-post comparison, significant(p<0.05). Study 2: Positive influence on daily functioning, positive trends on emotional state, self-reported general condition. Significant(p<0.05).
2. Sun J et al. [26]	n=97 (74.6 +/- 9.2) years.	Betaine, a zwitterionic quaternary ammonium compound (200 microgram/kg).	-Homocysteine levels - Tau Phosphorylation and phosphatase activity -memory-related and synaptic protein levels - ADAS-Cog analysis.	-Homocysteine level significantly elevated in malnourished (p<0.05) - Homocysteine levels and malnourishment results in AD - Betaine able to reduce hyperphosphorylation of Tau protein and increase phosphatase activity (P<0.05) -Betaine increases memory-related protein (NR1 & NR2A) (P<0.05) and synaptic proteins - Betaine cause a significant improvement in recall of words, visuospatial capacity, recognition of dual words.
3. Andrieu S et al. [28]	n=1680 Age>70 years.	Docosahexaenoic acid 800mg Eicosapentaenoic acid 225mg In Addition to multidomain intervention, omega 3 polyunsaturated fatty acids, placebo.	Composite Z-Score at 36 months.	Neutral Study. The multidomain intervention plus supplement showed improvement in composite Z-score which is not statistically significant.
4. Gleason CE et al. [33]	n= 65 (> 60 years).	Purified soy isoflavones (mainly Daidzin and Genistin) capsules; 100 mg/day.	Assessed at 3 & 6 months Study subjects were assessed for weekly dietary intake using FFQ. Cognitive domains specifically assessed include visual-spatial memory, visual-motor, verbal fluency, and dexterity. Isoflavone assays (Equol) were also measured. Grooved Pegboard; dominant and non-dominant hand.	Isoflavone increased significantly at 3 and 6 months compared to the placebo. Total plasma equol levels significantly correlated with a measure of speeded dexterity. Plasma equol levels and verbal fluency performance showed a positive association. Phonemic fluency has a positive correlation r=0.29, p=0.04.
5. Nolan JM et al. [36]	n=40 patients Trial 1, n=12 Trial 2, n=13 Trial 3, n=15 normal controls.	Trial/Formulation 1: xanthophyll carotenoids only. Trial/formulation 2: xanthophyll carotenoids along with fish oil.	Trials 1, 2, 3 measured serum conc. Of lutein (L) and meso zeaxanthin (MZ) at baseline and after 6 months after intervention In trial 2 LPC 22:6 and LPC 20:5 were measured at baseline and at 6 months to gauge DHA and EPA response respectively.	Patients on (Formulation 2) over 18 months show less Progression of AD compared (Formulation 1). 1. Clinical progression of AD was less in T2 compared to T1 (P=.003) 2. Patient carer reported functional benefits in memory, sight, and mood in T2 patients.
6. Stein MS et al. [41]	n=63 (age >60).	Open labeled, 3000 IU vitamin D2 for 8 weeks. Followed by Humulin-R (100IU/ml) - nasal insulin	Baseline assessment - ADAS-cog and DAD, Folstein MMSE, WMS-RLM; Serum calcium, albumin, creatinine, uric acid. Primary endpoint - ADAS-Cog, WMS-RLM immediate and delayed scores. Secondary endpoint-ADAS-cog word recall, word recognition; GDS, BPI.	Neutral study. ADAS-cog improved by a median (IR) of 9 with nasal insulin after placebo high-dose vitamin D (p = 0.02) but may represent regression to the mean as WLS-R LM did not change. Intranasal insulin benefits may be restricted to early disease.
7. Scheltens P et al. [44,46]	n=259 Mean age 73.8 (51-89)	Daily 125ml(125kcal) Nutricia Souvenaid - has FortasynTM Connect composed of: Eicosapentaenoic acid (EPA), 300mg, Docosahexaenoic acid (DHA), 1200mg, Phospholipids 106mg Choline 400mg Uridine monophosphate 625mg Vitamin E (alpha-tocopherol equivalents) 40mg, Vitamin C 80mg, Selenium 60µg, Vitamin B12 3µg Vitamin B6 1µg, Folic acid 400µg	The primary outcome assessed includes the memory function domain (NTB z score). Secondary outcomes-Executive function domain score. - using WMS-r Digit span, Category fluency, Trail making part A and B tests, Controlled oral word association test. PLI of various bands alpha, beta, theta, delta is analyzed on EEG. PLI marker of functional connectivity. Blood tests (Homocysteine levels, Vit E, RBC EPA, and DHA) to test for adherence.	-Improved NTB composite Z score at 24 weeks (p = 0.023; Cohen’s d = 0.21; 95% confidence interval [−0.06]–[0.49]). -No significant intervention effect on the NTB executive function domain. -Connectivity analysis (PLI) for the delta band revealed a significant in favor of the active group -increased erythrocyte DHA and EPA, plasma vitamin E, and decreased plasma homocysteine were detected in the active group, reported high compliance at 24 weeks.
8. Soininen H et al. [47]	n=311 (prodromal AD patients) Age not defined but participants have a diagnosis of AD.	Souvenaid, a daily supplement that contains FortasynTM Connect as the active ingredient composed of: Eicosapentaenoic acid, 300mg Docosahexaenoic acid, 1200mg Phospholipids 106mg Choline 400mg Uridine monophosphate 625mg Vitamin E (alpha-tocopherol equivalents) 40mg Vitamin C 80mg Selenium 60µg, Vitamin B12 3µg Vitamin B6 1µg, Folic acid 400µg	NTB composite Z-score over 24 months NTB Z-score was based on CERAD 10-word list learning immediate recall, CERAD 10-word delayed recall, CERAD 10-word recognition, category fluency, and the Letter Digit Substitution test.	IN NTB composite Z-score statistically significant findings include -CDR-SB -MRI total hippocampal volume reduction -MRI ventricular volume reduction. FortasynTM Connect has positive outcomes on attention, memory, and executive function when considered separately.
9. Remington R et al. [51]	n=106 Aged 77.8 ± 8.4 years.	NF-2 Tabs/day dose composed of: folic acid 400µg Vitamin B12 6ug alpha-tocopherol 30IU, S-Adenosylmethionine SAM 400mg (200 mg active iron) N-Acetyl Cysteine 600mg Acetyl-L-Carnitine 500mg Placebo-identical in appearance but inert.	Primary outcome-Cognitive outcome determined by Clox-1 and Age- and Education-Corrected Mayo’s Older Americans Normative Studies Scaled Score (AEMSS) of DRS-2 Secondary outcomes- BPSD and daily function determined by NPI and ADCS-ADL.	Improved Cognitive performance, memory at 3 months and improved with statistical significance (Clox-1 p = 0.0083, 95% CI [0.4481, 2.9343]; DRS-2 p = 0.0266, 95% CI [0.1722, 2.7171]). BPSD improved NPI improved 1.86-fold in NF group NF more effective in earlier stages of AD.
10. Remington R et al. [52]	n=24. Aged 78.4 +/- 5.7 years.	Nutraceutical formulation (NF) composed of: folic acid 400µg Vitamin B12 6ug alpha-tocopherol 30IU, S-Adenosylmethionine SAM 400mg (200 mg active iron) N-Acetyl Cysteine 600mg Acetyl-L-Carnitine 500mg prepared by Nutricap Labs.	Primary outcome-Cognitive performance determined by Clox-1 and DRS-2 Secondary outcomes-BPSD and daily function determined by NPI and ADCS-ADL.	-baseline, 3 months for 12 months. (Participants already on NF prior to study not de novo, so not improved). Participants did not display any significant or clinical change in cognitive performance of BPSD score over the course of 12 months. Crossover of placebo to NF showed improvement or maintenance paralleling There is no decrease in cognitive performance or BPSD over the course of 12 months observed in Placebo.