Young-Onset Dementia Tied to New Risk Factors ~ Domenico Pratico, MD, FCPP
- June 17, 2024

In most cases, Alzheimer’s disease develops after 65 and is considered the result of multiple factors
that, by interacting over time, will manifest clinically with a progressive decline in memory and
executive abilities. This form is also called late-onset Alzheimer’s disease. For the last few decades,
clinical studies have identified several risk factors for it. Some of them are defined as non-modifiable
(age, apolipoprotein E4, gender), but others are considered modifiable, such as high blood pressure
and type 2 diabetes.
On the other hand, the onset of dementia before the age of 65 is defined as early-onset, which in
most cases is secondary to a DNA mutation and also called genetic or familial Alzheimer’s disease.
Because of its inevitability if one inherits one of these mutations, this form of dementia has generally
been less investigated. However, in recent years, we have witnessed a significant increase in cases of
dementia that start well before 65 and are not genetic. Considering that the age of individuals with
early onset typically ranges from 45 to 64, it is counterintuitive that they represent a big portion of
what is considered the active component of the workforce within a society. With this concept in
mind, this new clinical observation could have a huge socio-economic impact on society as a whole.
One important question regarding these subjects, not fully answered, is: are the risk factors
responsible for early onset the same or different from the ones we know are important for late
onset? A possible answer to this question can be found in a recently published study, in which the
authors looked at 40- to 64-year-old individuals in search of factors that were potentially associated
with an increased risk of developing early-onset dementia over the years. Among the risk factors
that they found associated with a higher incidence of young-onset dementia were orthostatic
hypotension, depression, Vitamin D deficiency, high c-reactive protein, and social isolation.
The study is very interesting for two main reasons. First, for focusing on a less investigated form of
dementia; second, for bringing to light novel risk factors such as social isolation and depression,
besides confirming that, like for late-onset dementia, Vitamin D deficiency, high c-reactive protein,
and orthostatic hypotension are indeed to be considered risk factors.
Importantly, like for late-onset dementia, interventions aiming at correcting these modifiable risk
factors can be easily implemented. Although the study did not address this aspect, it is fair to predict
that, like for late-onset, by correcting these risks (social isolation, depression, etc.), a significant
number, up to 30 to 40%, of all cases of early-onset dementia could be reduced or prevented. This
result would have a tremendous worldwide impact on health systems, the socio-economic structure,
and most importantly, the regular daily life of many families. Let’s not forget that the subjects who
develop non-genetic early-onset dementia are probably fathers or mothers of young children or
grandparents of young grandchildren.
Domenico Praticò, MD, is the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research, Professor and Director of the Alzheimer’s Center at Temple, and Professor of Pharmacology at the Lewis Katz School of Medicine at Temple University
You can find out more information on Dr. Domenico Pratico’s research papers here.
Follow Dr Domenico Pratico‘s lab website here: Pratico Lab