Fight Aging!

There is now enough human data for immunotherapies that clear amyloid-β from the brain for researchers to say something useful and coherent about the effects of these drugs on Alzheimer's disease. It is clear that the effect size is nowhere close to the hoped for reversal of disease, and is small enough to be hard to detect without sizable patient populations or long-term follow up. This indicates that amyloid-β aggregation is not the most important pathological mechanism in later stages of the condition. It may well be the initially important mechanism that sets the stage for other forms of dysfunction, such as tau aggregation and neuroinflammation, but it will require years more to produce sufficient data in patients with early, mild cognitive symptoms to know whether or not these anti-amyloid immunotherapies can prevent Alzheimer's disease to any meaningful degree.

Alzheimer's patients and their families are faced with the tough question of whether to undergo a treatment that will not make them better. It won't even stop them from getting worse. At best, treatment with lecanemab or donanemab could slow the inevitable cognitive decline that characterizes Alzheimer's. Add to this the facts that treatment is expensive, requires biweekly or monthly infusions, and carries risks such as brain bleeds and brain swelling that are usually mild and go away on their own but can, in rare cases, be life-threatening. But just because the benefits are limited doesn't mean they are not valuable to patients and their families.

There are two critical inflection points on the continuum between independence and dependency. The first is the point where a person can no longer live independently because of an impaired ability to manage everyday tasks such as preparing meals, driving, paying bills and remembering appointments. The second point comes when a person can no longer care for his or her own body, and requires assistance with bathing, dressing, and toileting. To calculate the effects of treatment, researchers first estimated when people could expect to lose each of the two kinds of independence if left untreated. They analyzed the experiences of 282 people who participated in research studies. All participants met the criteria for treatment with the two new drugs, but hadn't received them previously. The researchers also calculated how quickly symptoms progressed without treatment.

Using these data on independence and progression, combined with the reported effects of the two drugs, the researchers calculated the amount of time a person at each stage of the disease could be expected to live or care for themselves independently without treatment, and how this progression would compare to those who received treatment. A typical person with very mild symptoms could expect to live independently for another 29 months without treatment, 39 months with lecanemab, and 37 months with donanemab. Most people with mild symptoms - as opposed to very mild symptoms - were already unable to live independently at baseline, so for them the more relevant measure was how much longer they would be able to care for themselves. The researchers calculated that a typical person at this stage of the disease could expect to manage self-care independently for an additional 26 months if treated with lecanemab, 19 months with donanemab.

Link: https://medicine.washu.edu/news/next-gen-alzheimers-drugs-extend-independent-living-by-months/