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Free keywords:
Dementia, cognitive aging, biomarkers, diagnostic criteria
Abstract:
The National Institute on Aging-Alzheimer's Association (NIA-AA)
guidelines for Alzheimer's disease (AD) propose the categorization of
individuals according to their biomarker constellation. Though the
NIA-AA criteria for preclinical AD and AD dementia have already been
applied in conjunction with imaging AD biomarkers, the application of
the criteria using comprehensive cerebrospinal fluid (CSF) biomarker
information has not been thoroughly studied yet. The study included a
monocentric cohort with healthy (N = 41) and disease (N = 22) controls
and patients with AD dementia (N = 119), and a multicentric sample with
healthy controls (N = 116) and patients with AD dementia (N = 102). The
CSF biomarkers beta-amyloid 1-42, total tau, and phosphorylated tau at
threonine 181 were measured with commercially available assays.
Biomarker values were trichotomized into positive for AD, negative, or
borderline. In controls the presence of normal CSF profiles varied
between 13.6 and 25.4 % across the studied groups, while up to 8.6 % of
them had abnormal CSF biomarkers. In 40.3-52.9 % of patients with AD
dementia, a typical CSF profile for AD was detected. Approximately 40 %
of the potential biomarker constellations are not considered in the
NIA-AA guidelines, and more than 40 % of participants could not be
classified into the NIA-AA categories with distinct biomarker
constellations. Here, a refined scheme covering all potential biomarker
constellations is proposed. These results enrich the discussion on the
NIA-AA guidelines and point to a discordance between clinical
symptomatology and CSF biomarkers even in patients with full-blown AD
dementia, who are supposed to have a clearly positive for AD
neurochemical profile.
