Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Tort-Merino A, Olives J, León M, Peñaloza C, Valech N, Santos-Santos MA, Càmara E, Grönholm-Nyman P, Martinez-Lage P, Fortea J, Molinuevo JL, Sànchez-Valle R, Laine M, Rodríguez-Fornells A, Rami L
Publisher: IOS Press
Publication year: 2019
Journal: Journal of Alzheimer's Disease
Journal acronym: J. Alzheimer´s Dis.
Volume number: 70
Issue number: 1
Start page: 211
End page: 225


Abstract

BACKGROUND:

We investigated a sample of
cognitively healthy subjects with normal Alzheimer's disease (AD)
cerebrospinal fluid (CSF) biomarker levels to identify the earliest
variables related to longitudinal memory changes.

OBJECTIVE:

Employing
a new highly demanding learning and memory test (the Ancient Farming
Equipment Test; AFE-T), we aimed to investigate whether a biomarker
related to neurodegeneration (i.e., CSF tau) was associated with
longitudinal memory decline.

METHODS:

Thirty-two
cognitively and biologically normal (CBN) subjects underwent MRI,
neuropsychological assessment, and the AFE-T at baseline and 18 months
later. To explore the relationship between cognitive performance and
relevant factors, a linear model was set up. For a secondary analysis
that further explore the effect of tau, the subjects were divided into
CBN-Tau↓ (tau < 228.64 pg/ml; n = 16) and CBN-Tau↑
(tau > 228.64 pg/ml; n = 16). We also performed voxel-based
morphometry (VBM) to identify regions of grey matter volume that would
predict both baseline and longitudinal cognitive performance.

RESULTS:

Our
main finding was an association between CSF tau and longitudinal memory
decline measured with AFE-T (B = -0.17, p < 0.05; r = -0.414;
p < 0.01), and further analyses showed different evolvement between
subgroups, with an accelerated decline in individuals with higher tau
(F(1,31) = 8.37; p < 0.01). VBM results suggested that AFE-T
performance is related to grey matter volume in a medial temporal,
middle frontal, and posterior cerebellar network at baseline, and that
there are strategic brain areas driving the longitudinal cognitive
changes.

CONCLUSIONS:

The present findings provide
evidence for structural and biological markers linked to cognitive aging
by highlighting the role of tau, a marker of neurodegeneration, which
can be related with the earliest memory changes in healthy subjects.


Keywords

Aging, biomarkers, cognition, early detection, memory decline, tau, Voxel-based morphometry

Last updated on 2020-04-04 at 05:05