in spite of my post on the lack of utility of vitamins in 3 studies, a new one popped up today ( see doi:10.1001/jama.2013.282834) finding benefit of vitamin E for mild-to-mod alzheimer’s dz (AD, as defined by mini-mental health exam scores 12-26 who were on anticholinergics). VA study of 600 pts in 13 different veterans affairs hospitals, randomized to vitamin E 1000IU bid, memantine 20 qd, both or neither/placebo. assessed several different outcomes, with primary outcome of results on Alzheimer’s Disease Cooperative Study/Activity of Daily Living Inventory (ADCS-ADL). Had drug company support. Findings:
–baseline: 86% white, 97% male, 57% with no more than high school educ, mean MMSE of 21, median CAS (caregiver activity survey) with 3 hours of caregiver time per day. followed up to 4 years, with median of 2.27 years
–42% not complete trial: ½ of whom died.
— ADCS-ADL decreased in all groups, but was 3.15 points higher in the vit E alone group (no clear defn of what is clinically significant, but they state that 2 points could be the difference leading to loss of independence in bathing or dressing). this translated to an effective delay in AD progression by 6.2 months (which is pretty impressive, compared to the drugs available). and this delay was largely sustained during the study (delay of 10.8 months at 1 year, 8.7 months at 2 yrs, 9.3 at 3 yrs, and 1.8 at 4 yrs). larger treatment effect in those with more severe AD
–of the other secondary outcomes (including MMSE), the only other one of with significant findings was CAS – increase in caregiver hours was 2.17 less in the vitamin E alone group
–adherence rates were pretty bad: 65% in all groups
–adverse effects: not higher in vit E group (of concern, prior meta-anal had shown increased mortality with vit E. of note here, the mortality in the vit E group trended to be less – 7.3%/yr, vs 9.4% in placebo. Not statistically significant). there was a significant increase in infections, but only in the memantine group.
–of possible importance: memantine alone did nothing over placebo, and the combo or memantine plus vit E was worse than either drug alone!!
so,
–trials showing memantine benefit are limited to those for patients with moderately severe dementia, and this trial reaffirms not to use it in those with mild to moderate dementia
–vitamin E ineffective in those with mild cognitive impairment, and this trial adds nothing to that conclusion
–this seems to me to be a well-done study, though limited by adherence (tough in this group), high death rate (pretty much expected in this group), loss to follow-up. given the lack of alternatives, seems reasonable to me to suggest vit E at a dose of 2000 IU/day without memantine in patients with mild to moderate AD (ie, MMSE in th 12-26 range). it is unclear in the study if patients stopped their anticholinergics (mostly donepezil) or not, though most likely they continued (and there is pretty good evidence that it helps with mild-to-mod AD).