Delaying Dementia Before We Can See It
Thursday, November 21st, 2019
The highest likelihood for successful treatment of dementia may be in the early or preclinical stages of the condition, when an individual does not show any symptoms but has beta-amyloid, or toxic protein clumps in the brain thought to cause dementia. Determining the effectiveness of treatments administered during this preclinical stage requires understanding of what early amyloid-related cognitive decline looks like in cognitively healthy adults.
How long does it take to see a meaningful decline in cognition?
For six years, researchers analysed how various cognitive tests changed over time in 1,120 cognitively healthy individuals across three international cohorts from Australia, Sweden, and North America. The recently published study found that on average, individuals in the preclinical stage of Alzheimer’s Disease started showing levels of performance similar to someone with mild cognitive impairment, within six years[1]. However, there was substantial variation between individuals, with some showing significantly less or hardly any decline across the six years, and some showing substantially more decline.
What does this mean for clinical trials?
The findings have sobering implications for clinical trials. Study participants’ cognitive decline was so gradual and variable over the first couple years that it would make it difficult to demonstrate that a drug is working – even if it is working – until three or four years in when the decline becomes more apparent. Even then, the variation in decline was such that the study analyses predicted that a clinical trial would need to enrol thousands of participants to detect what might be a considered a reasonable or modest treatment effect of 25-30% slowing of cognitive decline.
What can we do to speed up these trials?
Three to six years is a long time to wait to see if an experimental treatment can delay or prevent an onset of symptoms related to Alzheimer’s Disease. The study used a variety of measures to construct a composite cognitive score, in a cohort of people that lacked the diversity seen in the general population due to strict criteria regarding eligibility to participate in the trial. There is a need to develop more sensitive and reliable tests of cognition. A future goal could be to identify a biomarker highly correlated with cognition that can act as a proxy for cognitive decline so that trials can be shorter and require less participants. However, such an ideal is a long way-off. In the meantime, the study findings emphasise the importance of national drives to recruit more people into dementia research, through initiatives such as StepUp for Dementia Research.
[1] https://www.ncbi.nlm.nih.gov/pubmed/31289148
