A type of drug called antipsychotics may be prescribed to treat hallucinations, aggression and agitation. However, research has shown that some antipsychotics are associated with an increased risk of stroke and death in individuals with dementia.49-50 The decision to use antipsychotics must be considered with extreme caution. The FDA has ordered manufacturers to label such drugs with a “black box warning” about their risks and a reminder that they are not approved to treat dementia symptoms. Many factors contribute to the difficulty of developing effective treatments for Alzheimer’s. These include the slow pace of recruiting sufficient numbers of participants and sufficiently diverse participants to clinical studies, gaps in knowledge about the precise molecular changes and biological processes in the brain that cause Alzheimer’s disease, and the relatively long time needed to observe whether an investigational treatment affects disease progression. In addition, because mixed dementia is so common, even more brain changes than previously thought may be contributing to symptoms, further complicating decisions about which brain changes to target. 12 Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2021;17(3). Researchers believe that future treatments to slow or stop the progression of Alzheimer’s disease and preserve brain function may be most effective when administered early in the disease continuum, either at the MCI due to Alzheimer’s or preclinical Alzheimer’s phase. Biomarker tests, such as PET brain imaging and analysis of proteins in blood and CSF, will be essential to identify which individuals are in these phases of the continuum and should receive treatments when they are available. Biomarkers also will be critical for monitoring the effects of treatment. Biomarker tests are already playing an important role in drug development because they enable researchers to recruit into clinical trials only those individuals with the Alzheimer’s brain changes that a drug has been designed to affect.51 The most effective biomarker test or combination of tests may differ depending on where the individual is on the disease continuum and other factors.52 Nonpharmacologic Therapy Nonpharmacologic therapies are those that do not involve drugs. They are often used for people with Alzheimer’s dementia with the goal of maintaining or improving cognitive function, overall quality of life or the ability to perform activities of daily living. They also may be used with the goal of reducing behavioral symptoms such as depression, apathy, wandering, sleep disturbances, agitation and aggression. A recent review and analysis of nonpharmacologic treatments for agitation and aggression in people with dementia concluded that nonpharmacologic interventions seemed to be more effective than pharmacologic interventions for reducing aggression and agitation.53 Examples of nonpharmacologic therapies include computerized memory training, listening to favorite music as a way to stir recall, and using special lighting to lessen sleep disorders. As with current pharmacologic therapies, nonpharmacologic therapies do not slow or stop the damage and destruction of neurons that cause Alzheimer’s symptoms and make the disease fatal. Determining the effectiveness of nonpharmacologic therapies can be difficult because of the large number of unique therapies tested; the diversity of therapeutic aims (from improved overall quality of life to improvements in specific symptoms); the range of dementia stages represented (from mild to moderate to severe); the multiple types of dementia that may be present among participants in a particular study given the pervasiveness of mixed dementia; and the lack of a standard method for carrying out any individual therapy. With these multiple factors to consider, it is challenging to group together and compare nonpharmacologic therapies. Nevertheless, researchers have pooled data from multiple studies of nonpharmacologic therapies to provide insight into their potential effectiveness. • A meta-analysis54 found that aerobic exercise and a combination of aerobic and non-aerobic exercise had positive effects on cognitive function in people living with Alzheimer’s dementia.