Two studies in the May 19 issue of JAMA analyze the prevalence of the plaque amyloid among adults of varying ages, with and without dementia, and its association with cognitive impairment.
The earliest recognizable pathological event in Alzheimer’s Disease (AD) is cerebral amyloid-beta aggregation (protein fragments that clump together to form plaque).This pathology may be present up to 20 years before the onset of dementia.
Therefore, estimates of the prevalence of amyloid pathology in persons without dementia are needed to better understand the development of AD and to facilitate the design of AD prevention studies. Initiation of treatment for AD in the pre-dementia phase, when neuronal damage is still limited, may be crucial to have clinical benefit.
Led by Pieter Jelle Visser at VU University Medical Center in Amsterdam and Maastricht University, The Netherlands, these two studies compiled amyloid PET and cerebrospinal fluid (CSF) biomarker data from thousands of participants, and represent the largest data sets to date on how commonly amyloid builds up in people’s brains.
One meta-analysis looked at the prevalence of amyloid in cognitively normal people, and concluded that amyloid creeps into the brain 20 to 30 years before dementia can be diagnosed. This was particularly true for people who carry an ApoE4 allele; indeed, they developed amyloid at a younger age.
In the second study, the researchers compared amyloid prevalence among people clinically diagnosed with AD or other dementias, including dementia with Lewy bodies, frontotemporal dementia, and corticobasal syndrome. They found that the prevalence of brain amyloid in people diagnosed with most non-AD dementias was higher with increasing age. They concluded that older people may be likelier to have multiple pathologies, or to have been misdiagnosed. The data may help researchers set inclusion criteria for clinical trials, or make better diagnoses.
“The observation that key risk factors for AD-type dementia are also risk factors for amyloid positivity in cognitively normal persons provides further evidence for the hypothesis that amyloid positivity in these individuals reflects early AD,” the researchers wrote. “Our study also indicates that development of AD pathology can start as early as age 30 years, depending on the APOE genotype. Comparison with prevalence and lifetime risk estimates of AD-type dementia suggests a 20- to 30-year interval between amyloid positivity and dementia, implying that there is a large window of opportunity to start preventive treatments.”
However, the authors point out that follow-up studies need to be conducted since not all people with amyloid pathology develop dementia in their lifetime, and not all people with a clinical diagnosis of Alzheimer’s dementia have amyloid pathology.
“Because of the uncertainty about whether and when an amyloid-positive individual without dementia will develop dementia, amyloid positivity in these individuals should not be equated with impending clinical dementia but rather be seen as a risk state,” they wrote. “Our prevalence rates can be used as an inexpensive and noninvasive approach to select persons at risk for amyloid positivity.”