Key Points
-
Telltale brain changes begin decades before symptoms
-
New diagnostic guidelines define Alzheimer’s as a continuum
-
Without intervention, 315 million people worldwide with Preclinical AD are at risk
Preclinical Alzheimer’s is the first phase of Alzheimer’s disease, marked by changes in the brain that can precede symptoms, such as memory loss, by 20 to 30 years.
Identifying preclinical Alzheimer’s is now possible because of 21st-century technical advances, including neuroimaging developments, cerebrospinal fluid assays, and blood biomarker tests.
A Major Shift
This has led to a major shift in understanding Alzheimer’s disease (AD). For most of the century after it was first identified in 1906, AD was diagnosed according to cognitive and behavioral symptoms and could not be confirmed until a portmortem autopsy.
Today, it’s clearly seen as a biological disease, rather than a syndrome of effects. And it starts as Preclinical Alzheimer’s.
Three Stages
In 2011, the term Preclinical Alzheimer’s was widely introduced in new diagnostic guidelines published by a National Institutes on Aging – Alzheimer’s Association workgroup.
Their recommendations named three disease stages:
- Preclinical Alzheimer’s (neuropathological changes before symptoms)
- Mild Cognitive Impairment due to Alzheimer’s (cognitive changes not interfering with independence)
- Dementia due to Alzheimer’s (the symptomatic phase, progressing from mild to moderate to severe symptoms; this is the part formerly referred to as “Alzheimer’s”).
Revised Guidelines
In mid-2024, a follow-up workgroup revised criteria for the diagnosis and staging of Alzheimer’s disease. These Revised Guidelines define AD as existing on a continuum, beginning with neuropathologic changes in asymptomatic people and progressing through stages of increasing levels of disease-related brain changes that eventually lead to a progression of clinical symptoms.
Those early changes include abnormal levels of core biomarkers, particularly forms of the proteins amyloid beta and tau, such as phosphorylated tau-217.
Blood Tests
New simple blood tests have been developed in recent years that can measure these biomarkers in an inexpensive, relatively noninvasive way. Previously, samples of cerebrospinal fluid (such as from a spinal tap) or a brain imaging test (PET scan) were required.
Current FDA-approved blood tests are used mainly for research purposes and have not yet been recommended for use in primary care. This is expected to change quickly as more validated tests come on line, including, for example, at-home finger prick tests. [ideally a quote from Retain CSO would be here?].
About one in 8 Americans has Preclinical Alzheimer’s disease, as do about 315 million people worldwide.
In the absence of biomarker testing, most don’t know it. And it’s not known yet which individuals with Presymptomatic Alzheimer’s will go on to develop Alzheimer’s dementia.
Good News
For those not willing to chance it, however, there’s good news. Full-blown Alzheimer’s dementia disease develops gradually, over decades. This means there’s a long window of opportunity to delay or prevent Alzheimer’s dementia.
This insight works to the advantage not only of those with Preclinical Alzheimer’s but anyone who is concerned, fearful, or eager to optimize their brain health, as well as those who already know they’re at an elevated risk for AD due to a family history of dementia or because they know their biomarkers or a genetic elevated risk.
Among the goals of the 2024 Revised Guidelines, according to the Alzheimer’s Association, was to “lay a foundation that moves us toward personalized approaches for Alzheimer’s treatment that’s rooted in biology.”