In a new study, researchers found that accumulating amyloid—an abnormal protein linked to neurodegenerative conditions such as Alzheimer’s disease (AD)—occurred faster among people deemed to have “objectively-defined subtle cognitive difficulties” (Obj-SCD).
The new findings suggest that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded.
The research was done by a team at the University of California San Diego School of Medicine and elsewhere.
Classification of Obj-SCD, which has been previously shown to predict progression to mild cognitive impairment (MCI) and dementia, is determined using non-invasive but sensitive neuropsychological measures, including measures of how efficiently someone learns and retains new information or makes certain types of errors.
The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer’s disease.
These findings suggest that this is likely not the case for everyone and that sensitive neuropsychological measurement strategies capture subtle cognitive changes much earlier in the disease process than previously thought possible.
In the study, patients were enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), an on-going effort (launched in 2003) to test whether regular, repeated brain imaging, combined with other biological markers and clinical assessments, can measure the progression of MCI and early AD.
Seven hundred and forty-seven persons were involved in this study: 305 deemed cognitively normal, 153 with Obj-SCD and 289 MCI. All underwent neuropsychological testing and both PET and MRI scans.
The research team found that amyloid accumulation was faster in persons classified with Obj-SCD than in the cognitively normal group.
Those classified as Obj-SCD also experienced selective thinning of the entorhinal cortex, a region of the brain impacted very early in Alzheimer’s disease and associated with memory, navigation, and perception of time.
People with MCI had more amyloid in their brains at the start of the study, but they did not have a faster accumulation of amyloid compared to those with normal cognition.
However, those with MCI had more widespread temporal lobe atrophy, including the hippocampus.
Broadly speaking, scientists believe that for most people, AD is likely caused by a combination of genetic, lifestyle and environmental factors.
Increasing age is a primary, known risk factor. The amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kills neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia.
However, many scientists are now questioning the amyloid hypothesis given a large number of clinical trials in which drugs targeted and successfully cleared amyloid from the brain but did not impact the trajectory of cognitive decline.
The team says the ability to identify those at risk for AD before significant impairment and before or during the phase of faster amyloid accumulation would be a clinical boon.
This can provide both a way to monitor disease progression and a window of opportunity to apply potential preventive or treatment strategies.
One author of the study is Mark W. Bondi, Ph.D., professor of psychiatry at UC San Diego School of Medicine and the VA San Diego Healthcare System.
The study is published in Neurology.
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