A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease.
OBJECTIVE
(1) to assess the effect of 1 mg folic acid supplementation of cholinesterase inhibitors (ChI) in a 6 month double-blind placebo-controlled study of patients with Alzheimer's Disease (AD) and (2) to assess whether outcome measures were affected by changes in homocysteine levels.


METHODS
Fifty-seven consecutive outpatients with probable AD were treated concurrently with a ChI and either folic acid or placebo. None had conditions or medication known to interfere with folate metabolism. Fasting folate and homocysteine levels were measured prior to commencing ChI and 6 months later. Response was categorised using criteria of the National Institute of Clinical Excellence (NICE).


RESULTS
Twelve males and 29 females completed treatment (mean age 76.27 SD 6.23 years, Mini-Mental State Examination (MMSE) 23.49 SD 3.53, baseline homocysteine 18.39 SD 4.62 micromoles per litre). 23 received folic acid and 18 placebo. There were no significant baseline differences or use of individual ChI between the two arms. After 6 months a significant difference was seen in the change from baseline in combined Instrumental Activities of Daily Living and Social Behaviour scores between arms (folate+1.50 (SD 5.32) vs placebo -2.29 (SD 6.16) (p=0.03) but not change in MMSE scores. Sixteen of 23 subjects receiving folic acid and 7/18 placebo subjects were classified as NICE responders (p=0.05).


CONCLUSIONS
This pilot double blind study suggests that response to ChI in patients with AD may be improved by the use of folic acid. The relationship between any change in homocysteine levels and response to treatment is discussed.
Connelly
Peter J
PJ
Department of Psychiatry, University of Dundee, Murray Royal Hospital, Perth, UK. pjc@dementiaresearch.freeserve.co.uk
Prentice
Neil P
NP
Cousland
Gary
G
Bonham
Jim
J
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D019587:Dietary Supplements; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D005702:Galantamine / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008609:Mental Status Schedule; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D010919:Placebos; D000068836:Rivastigmine; D016896:Treatment Outcome; D014803:Vitamin B Complex; D014815:Vitamins / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D010919:Placebos; D014815:Vitamins; D005702:Galantamine; D006710:Homocysteine; D014803:Vitamin B Complex; D000077265:Donepezil; D005492:Folic Acid; D000068836:Rivastigmine