Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study.
BACKGROUND
Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Abeta(42) and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group.


METHODS
Patients with SCI, naMCI, aMCI, and neurologically healthy controls were recruited from 20 memory clinics across Europe, between January, 2003, and June, 2005, into this prospective cohort study. A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau. Patients were assessed annually up to 3 years. Outcome measures were changes in memory, overall cognition, mini-mental state examination (MMSE) score, daily function, and progression to AD-type dementia.


RESULTS
The CSF AD profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]) than in healthy controls (28 of 89 [31%]). The profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in patients with aMCI (MMSE and daily function). In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26.8, 95% CI 1.6-456.4).


CONCLUSIONS
AD is a common cause of SCI, naMCI, and aMCI and is associated with cognitive decline in patients with naMCI or aMCI. Patients with SCI might be in the early stages of AD, and cognitive decline might become apparent only after longer follow-up.


BACKGROUND
European Commission; Ana Aslan International Foundation.
Visser
Pieter Jelle
PJ
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, 6200 MD Maastricht, Netherlands. pj.visser@np.unimaas.nl
Verhey
Frans
F
Knol
Dirk L
DL
Scheltens
Philip
P
Wahlund
Lars-Olof
LO
Freund-Levi
Yvonne
Y
Tsolaki
Magda
M
Minthon
Lennart
L
Wallin
Asa K
AK
Hampel
Harald
H
Bürger
Katharina
K
Pirttila
Tuula
T
Soininen
Hilkka
H
Rikkert
Marcel Olde
MO
Verbeek
Marcel M
MM
Spiru
Luiza
L
Blennow
Kaj
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins