Preclinical Alzheimer’s unlikely to lead to dementia, new study reports

Preclinical Alzheimer’s unlikely to lead to dementia, new study reports

1200 829 Peter Stevenson, PhD

New data from a multi-study analysis has unveiled that preclinical Alzheimer’s disease (AD) will not lead to severe dementia in the majority of cases.

The paper marks the first time that biomarker test results have been taken into account when predicting the lifetime risk of AD. Two existing epidemiological cohort studies, which measured biomarkers for amyloidosis and neurodegeneration, were included in the analysis. The first was a 1,541-patient longitudinal study, which focused on the rates of transition from normal to abnormal biomarker states, by age, in individuals without dementia, as well assessing the rates of transition to dementia from an abnormal biomarker state.

The second source was a large dataset from Europe and the US, corresponding to 353 people with mild cognitive impairment (MCI), as well as amyloidosis and neurodegeneration, and a further 222 individuals with MCI and neurodegeneration.

These data were used to create a model that predicts the likelihood of AD progression, with sex and age identified as key factors in how the preclinical stage is likely to transition. For instance, in elderly populations, most people will die of other causes before AD becomes clinically significant. That being said, women – who generally live longer – have a higher risk of developing AD within their lifetimes.

Crucially, the analysis uncovered that the rates of disease progression escalated significantly depending on the biomarkers detected. A 70-year-old male with amyloidosis only, for example, has a lifetime risk of AD of just 20%. However, if neurodegeneration is added into the mix, the risk climbs to 31%. Add MCI, and the risk of AD skyrockets to 81%.

As such, the findings can be used to help guide clinicians in interpreting risk in the early stages. What’s more, they may have implications for research, as the authors also focused on 10-year risks, highlighting Alzheimer’s patients at the highest risk of dementia progression, i.e. those that should be prioritised for enrolment into clinical trials.

All things considered, the take-home message from the analysis is two-fold: for people with preclinical Alzheimer’s, there is some comfort to be found in knowing they are not destined to develop dementia. In addition, this new exploration of the prognostic markers indicative of disease progression means that clinicians can intervene earlier to help mitigate risks and offer prioritised treatment options wherever possible.

Further References:

Brookmeyer R. et al. (in press). Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimer’s and Dementia. DOI:

George J. (2018). Most Preclinical AD Doesn’t Progress to Dementia. MedPage Today. Available at:; accessed May 29, 2018.

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