Rapamycin rescues memory in Alzheimer's mice

A study involving over 1100 patients with mild to moderate Alzheimer's disease at 50 French clinics has revealed that receiving a comprehensive care plan involving regular 6-monthly assessments (with standardised guidelines for the management of problems) produced no benefits compared to receiving the usual care (an annual consultation). After two years, there was no significant difference in functional decline between the two groups, and no difference in the risk of being admitted to an institution or death.

A study involving outpatients with early stage Alzheimer’s found that their performance on some computerized tests of executive function and visual attention, including a simulated driving task, improved significantly after three months of taking cholinesterase inhibitors. Specifically, the drug treatment was associated with an improved ability to accurately maintain lane position during the simulated driving task; to accurately and quickly detect a target in a visual search task; to more quickly complete computerized mazes.

Although research has so far been confined to mouse studies, researchers are optimistic about the promise of histone deacetylase inhibitors in reversing age-related memory loss — both normal decline, and the far more dramatic loss produced by Alzheimer’s. The latest study reveals that memory impairment in the aging mouse is associated with altered hippocampal chromatin plasticity, specifically with the failure of histone H4 lysine 12 acetylation, leading to a failure to initiate the gene expression program associated with memory consolidation.

A special supplement in the Journal of Alzheimer's Disease focuses on the effects of caffeine on dementia and age-related cognitive decline. Here are the highlights:

A mouse study has found memory restoration and lower levels of amyloid-beta in Alzheimer’s mice following only 1-2 months of caffeine treatment. The researchers talk of “ a surprising ability of moderate caffeine intake to protect against or treat AD”, and define moderate intake as around 5 cups of coffee a day(!).

The Phase II clinical trial of a treatment using naturally occurring antibodies (IGIV) has achieved significantly lower rates of ventricular enlargement (6.7% vs 12.7% per year) and less whole-brain atrophy (1.6% vs 2.2% per year) than control subjects who initially received placebo. The trial ran for 18 months and involved 24 patients with mild to moderate Alzheimer's disease, of whom 16 received IGIV once or twice a month for the whole period, and 8 received a placebo for the first 6 months.

The American Academy of Neurology has updated its guidelines on when people with dementia should stop driving. While the guidelines point out that this decision is a complex one that should be made by a doctor using the Clinical Dementia Rating scale, they also supported caregivers’ instincts, which have been found to often be correct. For caregivers and family members, the following warning signs are identified:

A few months ago, I reported on an exciting finding that rapamycin, a drug currently used in transplant patients, improved memory in Alzheimer's mice. Now a different strain of mice (ones engineered to have defects in the genes that make amyloid precursor protein) has also shown improvements in learning and memory, correlated with less damage in brain tissue, after rapamycin treatment lowered levels of amyloid-beta-42. The mice given the drug performed at levels comparable with normal mice.

A European trial involving 225 patients with mild Alzheimer's has found that those who drank Souvenaid (a cocktail of uridine, choline and the omega-3 fatty acid DHA, plus B vitamins, phosopholipids and antioxidants) for 12 weeks were more likely to improve their performance in a delayed verbal recall task. 40% of the Souvenaid group showed improved performance compared to 24% of the placebo group. Those with the mildest cases of Alzheimer’s showed the most improvement. There was no improvement on the more general ADAS-cog test. Three further clinical trials, one in the U.S.