Age and diagnostic performance of Alzheimer disease CSF biomarkers.
OBJECTIVE
Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.


METHODS
We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis.


RESULTS
The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages.


CONCLUSIONS
Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, The Sahlgrenska Academy at University of Gothenburg, Mo¨lndal, Sweden. niklas.mattsson@neuro.gu.se
N
N
Mattsson
E
E
Rosén
O
O
Hansson
N
N
Andreasen
L
L
Parnetti
M
M
Jonsson
S-K
SK
Herukka
W M
WM
van der Flier
M A
MA
Blankenstein
M
M
Ewers
K
K
Rich
E
E
Kaiser
M M
MM
Verbeek
M
M
Olde Rikkert
M
M
Tsolaki
E
E
Mulugeta
D
D
Aarsland
P J
PJ
Visser
J
J
Schröder
J
J
Marcusson
M
M
de Leon
H
H
Hampel
P
P
Scheltens
A
A
Wallin
M
M
Eriksdotter-Jönhagen
L
L
Minthon
B
B
Winblad
K
K
Blennow
H
H
Zetterberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D016875:tau Proteins / Q000134:cerebrospinal fluid
D015415:Biomarkers; D016875:tau Proteins