Last month, researchers Francisco Lopera and colleagues reported in the journal Lancet Neurology that they were able to capture a clear decline in cognition starting in people’s early 30s in the largest-known population with autosomal-dominant (inherited) Alzheimer’s disease. They define an earlier disease stage prior to what is called pre-MCI, in effect pushing the line of detectability back toward younger ages by some four years.
Two other papers go in the same direction. Last year in the journal Brain, Mario Parra and colleagues published a new test that appears to detect a specific visual memory deficit perhaps even earlier, at ages when mutation carriers perform as well as controls on standard neuropsychometric tests. And in last December’s Annals of Neurology, Yakeel Quiroz and colleagues report the first of what is expected to be a wave of preclinical brain imaging findings. Carriers in their thirties, while still performing the memory test at hand as well as non-carriers, push their hippocampus harder to achieve that parity.
Together, these three papers push back the preclinical phase of Alzheimer’s that is detected by neuropsychology and imaging. They characterize the 20 to 15 years prior to symptoms of dementia.
Each of the previous familial Alzheimer’s disease studies was small. In this paper by Lopera and colleagues, the Colombian scientists retrospectively analyzed descendents of the largest-known cohort of autosomal-dominant Alzheimer’s, including 1,784 patients age 17 to 70 who came to Lopera for treatment and research between 1995 and 2010. This study is by far the biggest study of its kind. Four hundred forty-nine people carried the mutation. Four hundred ninety-nine non-carriers served to establish normal parameters on the battery of cognitive tests that the scientists administered to the participants at follow-ups every other year where possible. The studies are helping us get a better sense of the continuum of Alzheimer’s disease, from its asymptomatic stage into the mild cognitive impairment/prodromal stage, followed by the well characterized mild, moderate and severe dementia stage.