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

Abstract

OBJECTIVE

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).

DESIGN

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.

SETTING

Fifty-eight sites in the United States and Canada.

PARTICIPANTS

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.

RESULTS

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.

CONCLUSIONS

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.

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  • Authors+Show Affiliations

    ,

    Department of Neurology, Johns Hopkins School of Medicine, 1620 McElderry St, Reed Hall East 2, Baltimore, MD 21205, USA. ozioma@jhmi.edu

    , , , , , ,

    Source

    Archives of neurology 67:6 2010 Jun pg 688-96

    MeSH

    Activities of Daily Living
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Cognition Disorders
    Female
    Geriatric Assessment
    Humans
    Male
    Neuropsychological Tests
    Peptide Fragments
    Phosphorylation
    Psychiatric Status Rating Scales
    Regression Analysis
    Surveys and Questionnaires
    Threonine
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    20558388

    Citation

    Okonkwo, Ozioma C., et al. "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, pp. 688-96.
    Okonkwo OC, Alosco ML, Griffith HR, et al. Cerebrospinal fluid abnormalities and rate of decline in everyday function across the dementia spectrum: normal aging, mild cognitive impairment, and Alzheimer disease. Arch Neurol. 2010;67(6):688-96.
    Okonkwo, O. C., Alosco, M. L., Griffith, H. R., Mielke, M. M., Shaw, L. M., Trojanowski, J. Q., & Tremont, G. (2010). 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, 67(6), pp. 688-96. doi:10.1001/archneurol.2010.118.
    Okonkwo OC, et al. Cerebrospinal Fluid Abnormalities and Rate of Decline in Everyday Function Across the Dementia Spectrum: Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease. Arch Neurol. 2010;67(6):688-96. PubMed PMID: 20558388.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cerebrospinal fluid abnormalities and rate of decline in everyday function across the dementia spectrum: normal aging, mild cognitive impairment, and Alzheimer disease. AU - Okonkwo,Ozioma C, AU - Alosco,Michael L, AU - Griffith,H Randall, AU - Mielke,Michelle M, AU - Shaw,Leslie M, AU - Trojanowski,John Q, AU - Tremont,Geoffrey, AU - ,, PY - 2010/6/19/entrez PY - 2010/6/19/pubmed PY - 2010/7/6/medline SP - 688 EP - 96 JF - Archives of neurology JO - Arch. Neurol. VL - 67 IS - 6 N2 - OBJECTIVE: 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). DESIGN: 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. SETTING: Fifty-eight sites in the United States and Canada. PARTICIPANTS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/20558388/Cerebrospinal_fluid_abnormalities_and_rate_of_decline_in_everyday_function_across_the_dementia_spectrum:_normal_aging_mild_cognitive_impairment_and_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2010.118 DB - PRIME DP - Unbound Medicine ER -