Alzheimer Disease Markers Predict Subsequent Decline in Mild Cognitive Impairment

alzheimer's progression PET
alzheimer’s progression PET
Age and Alzheimer disease biomarkers are associated with decline in patients with mild cognitive impairment who initially reverted to normal cognition.

Age and abnormal Alzheimer disease biomarkers may be useful to predict subsequent disease progression in patients with mild cognitive impairment (MCI) who initially reverted to normal cognition, according to a study published in Neurology.

The investigators sought to identify potential biomarkers that could predict subsequent decline in individuals with MCI who reverted to normal cognition compared with MCI reverters who remain stable.

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The study included 61 individuals with MCI from the Alzheimer’s Disease Neuroimaging Initiative database who reverted to normal cognition at follow-up. The investigators compared markers of Alzheimer disease pathology (CSF amyloid, CSF tau, and amyloid PET), neurodegeneration imaging markers (FDG-PET, hippocampal volume, intracranial volume, and white matter hyperintensity volume), and other common biomarkers against the participants’ subsequent clinical outcomes (subsequent decline or stable reversion). Clinical findings from the Amsterdam Dementia Cohort were presented as an independent comparison in secondary analyses of MCI reverters.

After an average of 3.2±2.2 years, 16 participants (24%) progressed to MCI while 3 participants (5%) progressed to dementia. Participants who experienced subsequent decline were on average 5 years older than MCI reverters who maintained normal cognition; additionally, they had more abnormal Alzheimer disease biomarkers, specifically higher amyloid PET burden and higher CSF tau levels.

Limitations to the study included a relatively short follow-up period, in which it is possible that individuals in the stable group may decline again, and low reversion rates compared with the general population. Some individuals lost to follow-up — and therefore excluded from analysis — were older and more cognitively impaired, which may have further affected reversion rates.

The investigators suggest that age and certain biomarkers for Alzheimer disease can be associated with subsequent decline in patients with reverting MCI. These biomarkers may aid in the timely identification and prognosis of MCI reverters who may progress again in the long term.

Disclosure: Multiple authors declared affiliations with the pharmaceutical companies. Please refer to reference for a complete list of authors’ disclosures.


Vermunt L, van Paasen AJL, Teunissen CE, Scheltens P, Visser PJ, Tijms BM; Alzheimer’s Disease Neuroimaging Initiative. Alzheimer disease biomarkers may aid in the prognosis of MCI cases initially reverted to normal. Neurology. 2019;92(23):e2699-e2705.