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

A Tort-Merino; J Olives; M León; C Peñaloza; N Valech; MA Santos-Santos; E Càmara; Petra Grönholm-Nyman; P Martinez-Lage; J Fortea; JL Molinuevo; R Sànchez-Valle; Matti Laine; A Rodríguez-Fornells; L Rami

doi:10.3233/JAD-190046

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

A Tort-Merino, J Olives, M León, C Peñaloza, N Valech, MA Santos-Santos, E Càmara, Petra Grönholm-Nyman, P Martinez-Lage, J Fortea, JL Molinuevo, R Sànchez-Valle, Matti Laine, A Rodríguez-Fornells, L Rami

Research output: Contribution to journal › Article › Scientific › peer-review

12 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	211–225
Journal	Journal of Alzheimer's Disease
Volume	70
Issue number	1
DOIs	https://doi.org/10.3233/JAD-190046
Publication status	Published - 2019
MoE publication type	A1 Journal article-refereed

Keywords

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

Access to Document

10.3233/JAD-190046

https://content.iospress.com/articles/journal-of-alzheimers-disease/jad190046

Cite this

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. (2019). Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels. Journal of Alzheimer's Disease, 70(1), 211–225. https://doi.org/10.3233/JAD-190046

@article{716bff1fef604a9d971e0d98ca04c459,

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

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

author = "A Tort-Merino and J Olives and M Le{\'o}n and C Pe{\~n}aloza and N Valech and MA Santos-Santos and E C{\`a}mara and Petra Gr{\"o}nholm-Nyman and P Martinez-Lage and J Fortea and JL Molinuevo and R S{\`a}nchez-Valle and Matti Laine and A Rodr{\'i}guez-Fornells and L Rami",

year = "2019",

doi = "10.3233/JAD-190046",

language = "Odefinierat/ok{\"a}nt",

volume = "70",

pages = "211–225",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "IOS Press",

number = "1",

}

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 2019, 'Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels', Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 211–225. https://doi.org/10.3233/JAD-190046

TY - JOUR

T1 - Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels

AU - Tort-Merino, A

AU - Olives, J

AU - León, M

AU - Peñaloza, C

AU - Valech, N

AU - Santos-Santos, MA

AU - Càmara, E

AU - Grönholm-Nyman, Petra

AU - Martinez-Lage, P

AU - Fortea, J

AU - Molinuevo, JL

AU - Sànchez-Valle, R

AU - Laine, Matti

AU - Rodríguez-Fornells, A

AU - Rami, L

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - cognition

KW - memory decline

KW - Voxel-based morphometry

KW - early detection

KW - tau

KW - Aging

KW - biomarkers

KW - cognition

KW - memory decline

KW - Voxel-based morphometry

KW - early detection

KW - tau

KW - Aging

KW - biomarkers

KW - cognition

KW - memory decline

KW - Voxel-based morphometry

KW - early detection

KW - tau

KW - Aging

KW - biomarkers

U2 - 10.3233/JAD-190046

DO - 10.3233/JAD-190046

M3 - Artikel

SN - 1387-2877

VL - 70

SP - 211

EP - 225

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 1

ER -