This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
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.
GLOSSARY
- Aβ42=
- amyloid-β;
- AD=
- Alzheimer disease;
- MCI=
- mild cognitive impairment;
- NIA-AA=
- National Institute on Aging–Alzheimer's Association;
- pTau=
- hyperphosphorylated tau-181;
- RAVLT=
- Rey Auditory Verbal Learning Task;
- SNAP=
- suspected non-Alzheimer pathway;
- Tau=
- total tau;
- TMT=
- Trail Making Test;
- VAT=
- Visual Association Test
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received April 4, 2013.
- Accepted in final form July 11, 2013.
- © 2013 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Disputes & Debates: Rapid online correspondence
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within the last 8 weeks.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.