Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline in healthy older adults.
BACKGROUND
Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration.


OBJECTIVE
To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance.


METHODS
Retrospective analysis of longitudinal CSF biomarker levels and clinical data.


METHODS
A combined academic dementia disorder research center and dementia clinic.


METHODS
Thirty-seven cognitively healthy older volunteers (mean age, 73 years).


METHODS
Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive assessments at baseline and at follow-up 4 years later.


RESULTS
Low levels of CSF beta-amyloid(1-42) protein at follow-up were associated with decreased delayed word recall score on the Alzheimer Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P < .01) and with slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P < .001). Individuals with a decrease during the 4-year study of 15% or more in CSF beta-amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment Scale-cognitive subscale delayed word recall (z = -2.18, P < .05) and A Quick Test of Cognitive Speed (z = -2.35, P < .05) at follow-up. An increase over time of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P < .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein level (chi(2) = 10.47, P < .05) and with a higher CSF total tau protein level at follow-up (chi(2) = 8.83, P < .05). No correlation existed between baseline CSF biomarker levels and baseline or follow-up cognitive scores.


CONCLUSIONS
In this group of healthy older adults, changes in CSF biomarker levels previously associated with Alzheimer disease correlated with a decline in cognitive functions. Changes in CSF biomarker levels may identify early neurodegenerative processes of Alzheimer disease.
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. erik.stomrud@med.lu.se
Erik
E
Stomrud
Oskar
O
Hansson
Henrik
H
Zetterberg
Kaj
K
Blennow
Lennart
L
Minthon
Elisabet
E
Londos
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic / Q000379:methods*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins