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PMID: 20558388 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cerebrospinal fluid abnormalities and rate of decline in everyday function across the dementia spectrum: normal aging, mild cognitive impairment, and Alzheimer disease.

Archives of neurology ·Vol. 67 ·No. 6 ·2010-06-00 ·Pages 688-96

Okonkwo OC, Alosco ML, Griffith HR, Mielke MM, Shaw LM, Trojanowski JQ, Tremont G, Alzheimer's Disease Neuroimaging Initiative

Abstract

To investigate the effect of cerebrospinal fluid (CSF) abnormalities on the rate of decline in everyday function in normal aging, mild cognitive impairment (MCI), and mild Alzheimer disease (AD). Immunoassays of total tau (t-tau), tau phosphorylated at threonine 181 (p-tau(181)), and beta-amyloid 1-42 (Abeta(42)) concentrations were performed in CSF obtained from participants in the Alzheimer's Disease Neuroimaging Initiative. Random effects regressions were used to examine the relationship among CSF abnormalities, cognitive impairment (assessed with the Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-Cog]), and functional decline (assessed with the Pfeffer Functional Activities Questionnaire) and to determine whether the impact of CSF abnormalities on functional decline is mediated by cognitive impairment. Fifty-eight sites in the United States and Canada. One hundred fourteen cognitively intact adults, 195 patients with MCI, and 100 patients with mild AD. Main Outcome Measure Decline in the Pfeffer Functional Activities Questionnaire score. Abnormalities in all CSF analytes were associated with functional decline in MCI, and all but the t-tau:Abeta(42) ratio were associated with functional decline in controls. No abnormal CSF analyte was associated with functional decline in AD. Among controls, p-tau(181) concentration was the most sensitive to functional decline, whereas in MCI it was Abeta(42) concentration. Cerebrospinal fluid biomarkers were uniformly more sensitive to functional decline than the ADAS-Cog score among controls and variably so in MCI, whereas the ADAS-Cog score was unequivocally more sensitive than CSF biomarkers in AD. The impact of CSF abnormalities on functional decline in MCI was partially mediated by their effect on cognitive status. Across all diagnostic groups, persons with both tau and Abeta(42) abnormalities exhibited the steepest rate of functional decline. Abnormalities in CSF are associated with functional decline and thus with future development of AD in controls and patients with MCI. However, they do not predict further functional degradation in patients with AD. Persons with comorbid tau and Abeta(42) abnormalities are at greatest risk of functional loss.

MeSH Terms
Activities of Daily Living Aged Aged, 80 and over Alzheimer Disease/cerebrospinal fluid Amyloid beta-Peptides/cerebrospinal fluid Cognition Disorders/cerebrospinal fluid Female Geriatric Assessment Humans Male Neuropsychological Tests Peptide Fragments/cerebrospinal fluid Phosphorylation Psychiatric Status Rating Scales Regression Analysis Surveys and Questionnaires Threonine/metabolism tau Proteins/metabolism
Chemicals
Amyloid beta-Peptides Peptide Fragments amyloid beta-protein (1-42) tau Proteins Threonine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Okonkwo Ozioma C
Department of Neurology, Johns Hopkins School of Medicine, 1620 McElderry St, Reed Hall East 2, Baltimore, MD 21205, USA. [email protected]
Alosco Michael L
Griffith H Randall
Mielke Michelle M
Shaw Leslie M
Trojanowski John Q
Tremont Geoffrey
Alzheimer's Disease Neuroimaging Initiative
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Article Info
Journal
Archives of neurology
Abbr.
Arch Neurol
ISSN
1538-3687
DOI
10.1001/archneurol.2010.118
Email
[email protected]
Published
2010-06-00
Pages
688-96
Language
English
Region
United States
NLM ID
0372436
PMCID
PMC2888499
Subset
IM
Grants
NIA NIH HHS · T32 AG027668 · United States
NIA NIH HHS · U01 AG024904 · United States
NIA NIH HHS · U01 AG024904-01 · United States
NIA NIH HHS · U19 AG010483 · United States
External Links
PubMed source DOI: 10.1001/archneurol.2010.118 PMC Full Text
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