Alzheimer's disease , a progressive neurodegenerative disorder that affects millions worldwide, has a long preclinical stage. It potentially begins decades before clinical symptoms become apparent.
But as our new research suggests, blood biomarkers in combination with self-reported memory concerns could offer an early clue to how Alzheimer's disease develops across the life course.
This means midlife could be a critical window for promoting brain health.
For our study, we used data from the world-leading Dunedin Study at the University of Otago, which has been following a cohort of people for more than 50 years.
We found a certain protein known as pTau181 was associated with self-reported concerns about memory and thinking skills.
Notably, study participants were only 45 years old at the time of assessment. People typically aren't diagnosed with dementia until their 70s or older.
In recent years, we've seen advances in pharmaceutical treatments for Alzheimer's disease . However, these are not cures. At best, they slow disease progression but they don't preserve or restore cognitive function lost during more advanced stages.
It is likely these treatments work best when taken early, which makes it more important to identify the earliest signs of Alzheimer's disease.
Preventing dementia
Different types of dementia can look similar during the early stages of disease, but the treatment and course of progression differ significantly for each type of dementia.
In the past, Alzheimer's disease could only be definitively diagnosed postmortem, or more recently with invasive testing such as a lumbar puncture. But researchers are now working on identifying blood biomarkers that could offer a minimally invasive way to identify people at higher risk of developing Alzheimer's disease.
Detecting Alzheimer's disease in its earliest stages could provide an opportunity for prevention and offer the greatest benefits for brain health and ageing.
This may involve lifestyle changes , such as supporting people to be physically active and continuing to engage in social activities, and addressing modifiable risk factors such as hypertension or hearing loss.
Preventive approaches work more effectively the earlier they are implemented . Studying middle-aged populations is therefore important for identifying early risk profiles for Alzheimer's, long before the disease would be diagnosed.
When forgetfulness becomes a sign of disease
As people get older, they often notice their memory isn't as good as it used to be.
Forgetfulness is common and usually benign as people age. But in some people, these memory issues may indicate something else is going on.
Recent research shows subtle subjective changes in cognition often occur long before diagnosis and might be the first moment the disease is felt.
Screening for biological markers, in combination with subjective reports of memory function, could help distinguish the earliest signs of Alzheimer's disease pathology from normal ageing.
Proteins such as pTau181 are much higher in people with Alzheimer's disease, but we don't know yet when this protein begins to accumulate.
Our findings add to the growing evidence that the earliest signs of dementia may show up long before diagnosis. They also show that self-reported cognitive concerns may be an early warning sign for Alzheimer's, even in midlife.
Interestingly, we didn't find that the pTau181 biomarker was associated with MRI brain scan measures or cognitive test performance at age 45.
There are at least two possible explanations for this.
Perhaps pTau181 increases during the earliest stages of Alzheimer's disease, when people first start to notice their memory worsening but no changes are shown yet in MRI scans. Or it could be that elevated pTau181 is not related to Alzheimer's disease risk in midlife, and the protein is only useful for detecting Alzheimer's in older adults.
We don't know enough yet, but will be following the same group of people as they get older to continue this research.
Ashleigh Barrett-Young receives funding from the Neurological Foundation of New Zealand and the Health Research Council.
