Mild to moderate Alzheimer disease: alpha-Tocopherol slows functional decline

Although Vitamin-E and Memantine ( Ebixa, Namenda ) have been shown to have beneficial effects in moderately severe Alzheimer disease, evidence is limited in mild to moderate Alzheimer disease.

The aim of the study was to determine if Vitamin-E ( alpha-Tocopherol ), Memantine, or both slow progression of mild to moderate Alzheimer disease in patients taking an acetylcholinesterase inhibitor.

Researchers designed a double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate Alzheimer disease initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers.

Participants received either 2000 IU/d of alpha-Tocopherol ( n = 152 ), 20 mg/d of Memantine ( n = 155 ), the combination ( n = 154 ), or placebo ( n = 152 ).

The main measure was Alzheimer’s Disease Cooperative Study / Activities of Daily Living ( ADCS-ADL ) Inventory score ( range, 0-78 ). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures.

Data from 561 participants were analyzed ( alpha-Tocopherol = 140, Memantine = 142, combination = 139, placebo = 140 ), with 52 excluded because of a lack of any follow-up data.

Over the mean follow-up of 2.27 years, ADCS-ADL Inventory scores declined by 3.15 units ( adjusted P = 0.03 ) less in the alpha-Tocopherol group compared with the placebo group.
In the Memantine group, these scores declined 1.98 units less ( adjusted P = 0.40 ) than the placebo group’s decline.

This change in the alpha-Tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period.
Caregiver time increased least in the alpha-Tocopherol group.

All-cause mortality and safety analyses showed a difference only on the serious adverse event of infections or infestations, with greater frequencies in the Memantine ( 31 events in 23 participants ) and combination groups ( 44 events in 31 participants ) compared with placebo ( 13 events in 11 participants ).

Among patients with mild to moderate Alzheimer’s disease, 2000 IU/d of alpha-Tocopherol compared with placebo resulted in slower functional decline.
There were no significant differences in the groups receiving Memantine alone or Memantine plus alpha-Tocopherol.
These findings suggest benefit of alpha-Tocopherol in mild to moderate Alzheimer’s disease by slowing functional decline and decreasing caregiver burden. ( Xagena )

Dysken MW et al, JAMA 2014;311:33-44



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