Abstract
IntroductionEarly identification of Alzheimer’s disease (AD) is needed both for clinical trials and in clinical practice. In this study, we compared brief cognitive tests and cerebrospinal fluid (CSF) biomarkers in predicting conversion from mild cognitive impairment (MCI) to AD.MethodsAt a memory clinic, 133 patients with MCI were followed until development of dementia or until they had been stable over a mean period of 5.9 years (range 3.2–8.8 years). The Mini-Mental State Examination (MMSE), the clock drawing test, total tau, tau phosphorylated at Thr181 (P-tau) and amyloid-β1–42 (Aβ42) were assessed at baseline.ResultsDuring clinical follow-up, 47% remained cognitively stable and 53% developed dementia, with an incidence of 13.8%/year. In the group that developed dementia the prevalence of AD was 73.2%, vascular dementia 14.1%, dementia with Lewy bodies (DLB) 5.6%, progressive supranuclear palsy (PSP) 4.2%, semantic dementia 1.4% and dementia due to brain tumour 1.4%. When predicting subsequent development of AD among patients with MCI, the cognitive tests classified 81% of the cases correctly (AUC, 0.85; 95% CI, 0.77–0.90) and CSF biomarkers 83% (AUC, 0.89; 95% CI, 0.82–0.94). The combination of cognitive tests and CSF (AUC, 0.93; 95% CI 0.87 to 0.96) was significantly better than the cognitive tests (p = 0.01) and the CSF biomarkers (p = 0.04) alone when predicting AD.ConclusionsThe MMSE and the clock drawing test were as accurate as CSF biomarkers in predicting future development of AD in patients with MCI. Combining both instruments provided significantly greater accuracy than cognitive tests or CSF biomarkers alone in predicting AD.
Highlights
Identification of Alzheimer’s disease (AD) is needed both for clinical trials and in clinical practice
AD is generally preceded by an incipient preclinical phase [4], which progresses to mild cognitive impairment (MCI) [5] and to dementia [6]
The MCI criteria proposed by Petersen and colleagues were applied [21], i.e. 1) memory complaints of the patient, but preferable acknowledged by an informant; 2) objective memory impairment in relation to age and education, assessed by the physician; 3) a relatively preserved general cognition based on the physicians structural interview and a Mini-Mental State Examination (MMSE) score of at least 24 points; 4) intact or very slightly impaired ADL; and 5) not fulfilling the DSM-IIIR criteria for dementia [22]
Summary
Identification of Alzheimer’s disease (AD) is needed both for clinical trials and in clinical practice. We compared brief cognitive tests and cerebrospinal fluid (CSF) biomarkers in predicting conversion from mild cognitive impairment (MCI) to AD. The early identification of Alzheimer’s disease (AD) is becoming increasingly important so that the correct care and follow-up can be initiated [1,2]. A most successful biomarker-based method of predicting the conversion from MCI to AD has been the analysis of cerebrospinal fluid (CSF) and in particular total tau (tau), tau phosphorylated at Thr181 (P-tau) and the 42-amino-acid isoform of amyloid-b1–42 (Ab42). These analyses have provided classification accuracies of around 80% or even more. These analyses have provided classification accuracies of around 80% or even more. [7,8,9] these analyses are not available everywhere, and are unlikely to become a standard procedure because of the increasing prevalence of dementia, especially in developing countries, and the fact that the majority of patients must be evaluated in primary care
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