Cognitive training to reduce incidence of cognitive impairment in older adults

PROJECT SUMMARY Dementia is the most expensive medical condition in the US. There is an urgent need to intervene to curb the increasing prevalence of dementia in our population. Strong preliminary data from more than 18 ran- domized clinical trials demonstrate that computerized, cognitive speed of processing training (SPT) im-

proves cognition and transfers to improved instrumental activities of daily living. Recent evidence further indicates that SPT may reduce dementia risk. Analyses of 10-year data from the ACTIVE trial revealed that older adults randomized to SPT were 29% less likely to develop dementia. Moreover, those who com-

pleted additional training had a 48% reduced risk of dementia across 10-years. Two limitations of this study were a lack of clinical diagnosis of dementia and use of a no-contact control condition. Thus, an im- portant question is, “Can SPT be successfully implemented to reduce incidence of mild cognitive impair-

ment (MCI) or dementia?”. Our primary goal is to test the effectiveness of SPT to reduce incidence of MCI or dementia. The Preventing Alzheimer's with Cognitive Training-PACT field trial advances prior research by rigorously implementing SPT in a large population of cognitively normal older adults and ex-

amining the primary endpoint of MCI or dementia clinical diagnoses. Older adults are randomized to SPT or an active control arm of cognitive stimulation (i.e., computer games) and progression to MCI or demen- tia will be clinically assessed after 3-years. We further will explore if SPT effects are moderated by the de-

gree of amyloid pathology or apolipoprotein E4 status. To demonstrate feasibility, our investigative team is implementing the study protocol in an R56 phase and successfully enrolled 744 older adults at the time of proposal submission. Three years after enrollment, we will re-assess study participants to identify those

exhibiting cognitive decline. Such participants will be provided a thorough medical evaluation to clinically ascertain MCI or dementia diagnosis. Those classified as MCI or dementia will further complete an amy- loid PET scan and genetic testing. This non-pharmacological prevention trial is innovative with a highly

efficient experimental design and optimized SPT training protocols including an active control group. The proposed research will determine if SPT successfully reduces incidence of MCI or dementia. This out- come will be significant in that if an intervention can delay the onset of dementia by only one year, there

will be ~9.2 million fewer cases of the disease by 2050, substantially reducing cost. Positive results would support use of a relatively inexpensive and easy to apply intervention that could delay or prevent the on- set of Alzheimer’s disease and/or related dementias. Such an outcome would justify further research to

identify mechanisms of action. Results will inform clinical practice of effective interventions to attenuate age-related cognitive and functional decline and thereby improve public health.