Prevention, Not Cure, as a Way Forward in Alzheimer’s Disease

Many of us have read with dismay of recent clinical trial failures in Alzheimer’s disease. Are researchers and pharma companies wrong in considering amyloid as a target for therapies? Not necessarily. As a recent cover article in Newsweek points out, the problem with many of these trials may not be the target but the point at which trial participants are being treated. Older trials enrolled subjects who had apparent symptoms of Alzheimer’s disease and had received the diagnosis from physicians; however, many were found in postmortem studies to have suffered from other forms of dementia. Subject selection has been refined in more recent years using PET scans to ensure that clinically diagnosed patients actually had elevated biomarkers and thus had Alzheimer’s disease prior to trial enrollment. This has still not resulted in a successful trial, let alone an effective therapy. It turns out that by the time current screening techniques can identify subjects with Alzheimer’s, neuronal damage has already been taking place for at least 10 years. Researchers are thus increasingly focusing on the concept that the disease must be treated pre-symptomatically. Several prevention trials are focusing on elderly subjects who are cognitively normal but have elevated amyloid levels in the CNS or who have the APOE4 gene, a major risk factor for the disease; it is not a foregone conclusion that they will get Alzheimer’s, but they are at elevated risk. And other research groups are focusing on families with genetic variants that result in early onset Alzheimer’s disease. Performing trials earlier in the disease process is an extremely important step. But how soon? Too soon and the costs of the therapy may be too high to be acceptable to insurance companies, too late and the therapy will be ineffective. “MCI [mild cognitive impairment] is the sweet spot in terms of the cost of trials, the cost of drugs and quality of life for patients,” Howard Fillit, CEO of the Alzheimer’s Drug Discovery Foundation says in the Newsweek article. “That’s still prevention because you’re preventing dementia.”