Preclinical AD predicts decline in memory and executive functions in subjective complaints.
OBJECTIVE
We assessed whether preclinical Alzheimer disease (AD) based on CSF biomarkers at baseline predicts decline in cognitive functioning as measured by repeated neuropsychological tests for 4 cognitive domains in patients with subjective complaints.


METHODS
We included 132 patients with subjective complaints from our memory clinic-based Amsterdam Dementia Cohort, who underwent lumbar puncture and had repeated (range 2-7) neuropsychological evaluations. Follow-up was 2 ± 1 years. CSF biomarkers amyloid-β (Aβ42), total tau (Tau), and hyperphosphorylated tau-181 were used to define National Institute on Aging-Alzheimer's Association (NIA-AA) preclinical AD stages. Predictive value of preclinical AD stages as defined by CSF biomarkers, individual biomarkers, and Aβ42/tau ratio was assessed using linear mixed models. Outcome measures were compound z scores for memory, attention, executive functioning, language, and global cognition. Analyses were adjusted for age, sex, and education.


RESULTS
Patients were 61 ± 8 years old; 56 (42%) were women. Average baseline Mini-Mental State Examination score was 28.3 ± 1.5. Patients who fulfilled criteria for preclinical AD (stage 1: n = 11 + stage 2: n = 10) showed decline over time in memory (β ± SE -0.41 ± 0.14, p < 0.01), executive functions (-0.21 ± 0.08, p < 0.01), and global cognition (-0.29 ± 0.10, p < 0.01). There were no differences in cognitive decline between NIA-AA preclinical AD stages 1 and 2. In patients with normal CSF biomarkers, we observed memory improvement (0.19 ± 0.07, p < 0.01) and stable performance in all other domains.


CONCLUSIONS
CSF evidence of preclinical AD in patients with subjective complaints predicted cognitive decline over time, encompassing more than memory alone. Executive functioning and global cognitive functioning also deteriorated. On the other hand, 2-year prognosis for patients without evidence of AD pathophysiology was good.
From the Alzheimer Center (A.C.v.H., L.L.S., P.J.V., T.K., P.S., W.M.v.d.F.), Department of Neurology (A.C.v.H., L.L.S., P.S., W.M.v.d.F.), Neuroscience Campus Amsterdam (A.C.v.H., L.L.S., C.E.T., P.J.V., P.S., W.M.v.d.F.), Department of Clinical Chemistry (C.E.T., M.A.B.), Department of Medical Psychology (T.K.), and Department of Epidemiology/Biostatistics (W.M.v.d.F.), VU University Medical Center, Amsterdam; and the Department of Psychiatry and Neuropsychology/Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neurosciences, Maastricht University Medical Center, Maastricht, the Netherlands.
Argonde C
AC
van Harten
Lieke L
LL
Smits
Charlotte E
CE
Teunissen
Pieter J
PJ
Visser
Teddy
T
Koene
Marinus A
MA
Blankenstein
Philip
P
Scheltens
Wiesje M
WM
van der Flier
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000145:classification / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D018450:Disease Progression; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D062706:Prodromal Symptoms; D011379:Prognosis; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins