Alzheimer’s disease has become the leading medical problem in adults with Down syndrome due to the chromosomal alteration and the increase in life expectancy of this population, with a risk of more than 90% of developing dementia throughout their lives
A study led by Juan Fortea and Laura Videla, researchers at the Hospital de la Santa Creu i Sant Pau Research Institute – IIB Sant Pau and the Catalan Down Syndrome Foundation (FCSD) have described the risk of developing the clinical symptoms of Alzheimer’s disease over time and the influence of age from the preclinical phase, as well as the associated progressive cognitive deterioration.
These results, published in the journal JAMA Network Open, reinforce the importance of developing specific health plans and monitoring people with Down syndrome to assess their cognitive performance before the fourth decade of life.
The researchers examined the clinical progression of a cohort of 632 adults with Down syndrome. In the first evaluation, a total of 436 individuals with Down syndrome without clinical symptoms of Alzheimer’s disease, 69 patients with Alzheimer’s disease in the prodromal phase, that is, with cognitive impairment but without functional interference, and 127 with Alzheimer’s disease were included. Alzheimer’s disease.
At 5 years of follow-up, it was found that 17% of all asymptomatic participants had progressed to symptomatic phases of the disease (prodromal or dementia). When studying the influence of age on the asymptomatic phase of Alzheimer’s disease, they found that the progression to symptomatic phases before the age of 40 was practically nil, but that it progressively increased to rates of almost 60% in those over 50 years of age . However, this relationship with age was not observed in the group of patients with prodromal Alzheimer’s disease, who progressed to the stage of dementia regardless of age.
According to Laura Videla, a neuropsychologist at the IIB Sant Pau and the FCSD, among the patients who were in the prodromal phase of the disease at the start of the study, it was found that half of them had progressed to dementia after two years of follow-up and , at 5 years, practically all.
These estimates of the risk of progression are important data to take into account when designing specific health plans for adults with Down syndrome and for the design of clinical trials for Alzheimer’s disease. “These results reinforce the hypothesis that these patients do not deteriorate due to age, but due to Alzheimer’s itself. Now we know that in asymptomatic phases age does matter, but in prodromal phases it really doesn’t.”
Cognitive evolution over time
People with Down syndrome have an underlying intellectual disability that can be mild, moderate, severe, or profound. It is also known that from 35-40 years of age the cognitive performance of these patients begins to decline.
Another conclusion of this study is that both mild and moderate cases have a similar cognitive loss. As detailed by Laura Videla, “what we have seen is that, transversally, at the first visit people with mild intellectual disability score higher than those with moderate intellectual disability, but we wanted to see if the longitudinal cognitive impairment was also greater in one group than in another. And what we saw is that no, that they overlap here. In other words, the group of people with mild intellectual disability and the group of people with moderate intellectual disability lose the same number of points in the neuropsychological tests over time regardless of whether they start from a higher or lower baseline level”.
These findings could also be useful for the design of new clinical trials. For example, “to assess the effect of a certain treatment, it would not be necessary to divide the sample into two groups and, therefore, the sample size could be smaller and, with it, the study more efficient”, concludes the researcher.
Reference article
Videla L, Benejam B, Pegueroles J, et al. Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome. JAMA Netw Open. 2022;5(8):e2225573. doi:10.1001/jamanetworkopen.2022.25573
