The predictive power of Alzheimer's disease biomarkers in the preclinical phase

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Predictive Ability of Biomarkers in Preclinical Alzheimer Disease

The predictive power of Alzheimer's disease biomarkers in the preclinical phase

Review by Jennifer Rose V.
Molano, MD

Biomarkers in cognitively normal adults predict cognitive and neuropathological outcomes in Alzheimer's disease
.

People with Alzheimer's disease (AD) may be asymptomatic
for years prior to cognitive decline.
In this study, the researchers analyzed whether amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in cognitively normal adults living in the community predicted cognitive outcomes and AD neuropathological outcomes
.
AD biomarker status
is determined by PET imaging and preset thresholds for CSF p-tau 181/amyloid-β42 levels within 1 year after baseline clinical evaluation.
Cognitive outcomes are based on clinical assessment (validated) of clinical and functional competence, and pathological changes in AD are determined according to established criteria
.

Among 720 participants (mean age, 69 years; 58% are female; 86% were Caucasian), 22% were positive
for AD biomarkers at baseline.
Among biomarker-positive participants, 34% developed cognitive impairment after an average of 4 years of follow-up, compared with only 8%
of biomarker-negative participants.
Among participants whose dementia progressed clinically, 80 percent of biomarker-positive participants were clinically diagnosed with AD, compared with 55 percent
of biomarker-negative participants.
A positive AD biomarker, carrier of apolipoprotein E Ɛ4, a high risk score for polygenetics, and older age all increase the risk of
cognitive impairment.

Of the 82 participants, 70 percent underwent autopsies
.
More than 90% of biomarker-positive participants had AD neuropathological changes, compared with 9%
of biomarker-negative participants.
For AD neuropathology, preclinical biomarkers have 87% sensitivity, as well as more than 90% specific, positive, and negative predictive values
.
Participants with AD biomarker negative who develop cognitive impairment are more likely to present with non-AD pathology
.

comments

These results suggest that AD biomarkers have the potential to predict who will develop AD
in the asymptomatic or preclinical stages.
Longitudinal, comprehensive neuropsychological evaluation, combined with AD biomarkers, has the potential to further our understanding of these predictions, especially in patients with
subjective cognitive complaints.

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Commented on the article

Long JM et al.
Preclinical Alzheimer’s disease biomarkers accurately predict cognitive and neuropathological outcomes.
Brain 2022 Jul 22; [e-pub].
(https://doi.
org/10.
1093/brain/awac250)

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