Abstract
With promising results in recent treatment trials for Alzheimer’s disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI). This study investigates the potential of neuropsychological testing (NPT) to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes. Patients were divided into an early stage and a late stage group according to their Mini Mental State Examination (MMSE) score and labeled as AD or non-AD patients based on a post-mortem validated threshold of the ratio between total tau and beta amyloid in the cerebrospinal fluid (CSF; Total tau/Aβ(1–42) ratio, TB ratio). All patients completed the established Consortium to Establish a Registry for Alzheimer’s Disease—Neuropsychological Assessment Battery (CERAD-NAB) test battery and two additional newly-developed neuropsychological tests (recollection and verbal comprehension) that aimed at carving out specific Alzheimer-typical deficits. Based on these test results, an underlying AD (pathologically increased TB ratio) was predicted with a machine learning algorithm. To this end, the algorithm was trained in each case on all patients except the one to predict (leave-one-out validation). In the total group, 82% of the patients could be correctly identified as AD or non-AD. In the early group with small general cognitive impairment, classification accuracy was increased to 89%. NPT thus seems to be capable of discriminating between AD patients and patients with cognitive impairment due to other neurodegenerative or vascular causes with a high accuracy, and may be used for screening in clinical routine and drug studies, especially in the early course of this disease.
Highlights
While the global number of patients with Alzheimer’s disease (AD) is increasing, recent clinical trials suggest for the first time the possibility of devising a disease-modifying treatment
This study investigates the potential of neuropsychological testing (NPT) to identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes
While it seems that NPT might contribute to a risk-free early diagnosis of AD, it should be validated with established biomarkers like Aβ(1–42) and tau protein to reduce the risk of circular reasoning in predicting clinical diagnoses based on clinical neuropsychological assessments (Haldenwanger et al, 2010; Fields et al, 2011; Nelson et al, 2012, for previous work on relationships between NPT results and non-clinical biomarkers)
Summary
While the global number of patients with Alzheimer’s disease (AD) is increasing, recent clinical trials suggest for the first time the possibility of devising a disease-modifying treatment (among others, Sevigny et al, 2016). Specific neuropsychological testing (NPT) might represent such a method, with a substantial body of evidence demonstrating its potential for differential diagnosis (Edmonds et al, 2015; Haanpää et al, 2015; Mansoor et al, 2015) and prognosis estimation (Landau et al, 2010; Peters et al, 2014). While it seems that NPT might contribute to a risk-free early diagnosis of AD, it should be validated with established biomarkers like Aβ(1–42) and tau protein to reduce the risk of circular reasoning in predicting clinical diagnoses based on clinical neuropsychological assessments (Haldenwanger et al, 2010; Fields et al, 2011; Nelson et al, 2012, for previous work on relationships between NPT results and non-clinical biomarkers)
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