Cerebrospinal fluid profiles and prospective course and outcome in patients with amnestic mild cognitive impairment.
To examine the effect of specific cerebrospinal fluid (CSF) profiles on the rate of cognitive decline, disease progression, and risk of conversion to Alzheimer disease (AD) dementia in patients with amnestic mild cognitive impairment (MCI).Total tau (T-tau), tau phosphorylated at threonine 181, and β-amyloid 1-42 peptide (Aβ42) were immunoassayed in CSF samples obtained from patients with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative. Patients were then stratified by CSF profiles: (1) normal T-tau and normal Aβ42 (ie, normal-T-tauAβ42), (2) normal T-tau but abnormal Aβ42 (ie, abnormal-Aβ42), (3) abnormal T-tau but normal Aβ42 (ie, abnormal-T-tau), and (4) abnormal T-tau and abnormal Aβ42 (ie, abnormal-T-tauAβ42).Fifty-eight sites in the United States and Canada.One hundred ninety-five patients with MCI.A composite cognitive measure, the Clinical Dementia Rating Scale-sum of boxes subscale, and conversion to AD dementia.Patients with MCI with a CSF profile of abnormal-Aβ42 or abnormal-T-tauAβ42 experienced a faster rate of decline on the composite cognitive measure and the Clinical Dementia Rating Scale-sum of boxes subscale compared with those with normal-T-tauAβ42. They also had a greater risk of converting to AD dementia relative to the normal-T-tauAβ42 group. In contrast, those with a CSF profile of abnormal-T-tau did not differ from the normal-T-tauAβ42 group on any outcome. These findings were generally replicated when the sample was reclassified by patterns of tau phosphorylated at threonine 181 and Aβ42 abnormalities.β-Amyloid abnormalities but not tau alterations are associated with cognitive deterioration, disease progression, and increased risk of conversion to AD dementia in patients with MCI. Patients with abnormal Aβ42 may be prime candidates for drug treatment and clinical trials in MCI.
Okonkwo, OC; Mielke, MM; Griffith, HR; Moghekar, AR; O'Brien, RJ; Shaw, LM; Trojanowski, JQ; Albert, MS; Alzheimer's Disease Neuroimaging Initiative,
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