In this post, I link to and excerpt from Petrazzuoli F, Vestberg S, Midlov P, Thulesius H, Stomrud E, Palmqvist S. Brief cognitive tests used in primary care cannot accurately differentiate mild cognitive impairment from subjective cognitive decline. J Alzheimers Dis. 2020;75(4):1191-1201. [PMC free article] [PubMed] [Google Scholar] [Full-Text PDF]
All that follows is from the above resource.
Abstract
Background:
Differentiating mild cognitive impairment (MCI) from subjective cognitive decline (SCD) is important because of the higher progression rate to dementia for MCI and when considering future disease-modifying drugs that will have treatment indications at the MCI stage.
Objective:
We examined if the two most widely-used cognitive tests, the Mini-Mental State Examination (MMSE) and clock-drawing test (CDT), and a test of attention/executive function (AQT) accurately can differentiate MCI from SCD.
Methods:
We included 466 consecutively recruited non-demented patients with cognitive complaints from the BioFINDER study who had been referred to memory clinics, predominantly from primary care. They were classified as MCI (n = 258) or SCD (n = 208) after thorough neuropsychological assessments. The accuracy of MMSE, CDT, and AQT for identifying MCI was examined both in training and validation samples and in the whole population.
Results:
As a single test, MMSE had the highest accuracy (sensitivity 73%, specificity 60%). The best combination of two tests was MMSE < 27 points or AQT > 91 seconds (sensitivity 56%, specificity 78%), but in logistic regression models, their AUC (0.76) was not significantly better than MMSE alone (AUC 0.75). CDT and AQT performed significantly worse (AUC 0.71; p < 0.001–0.05); otherwise no differences were seen between any combination of two or three tests.
Conclusion:
Neither single nor combinations of tests could differentiate MCI from SCD with adequately high accuracy. There is a great need to further develop, validate, and implement accurate screening-tests for primary care to improve accurate identification of MCI among individuals that seek medical care due to cognitive symptoms.
Keywords: AQT, clock drawing test, cognitive screening, diagnostic accuracy, mild cognitive impairment, Mini-Mental State Examination, subjective cognitive decline
INTRODUCTION
MCI differs from dementia in that it is not severe enough to interfere with independence in daily life, but still causes a significant decline in cognitive function. Recent clinical and population-based samples suggest an MCI prevalence of 10% to 20% for adults aged 65 years and older [4–6].
The underlying etiology of MCI is very heterogenous, ranging from reversible causes such as depression to permanent or progressive pathological findings such as AD-related changes, cerebrovascular changes, hippocampal sclerosis, effect of trauma, metabolic diseases, etc. [8–10].
Accurate detection of MCI is time-consuming and requires a comprehensive neuropsychological assessment. However, most patients are examined in primary care and therefore there is a strong need for reliable and valid brief screening instruments for the detection of MCI [15]. There are many previous studies examining the identification of MCI, but unfortunately almost all of them focus on differentiating MCI from cognitively healthy controls that do not experience any cognitive symptoms [16–18]. There is therefore a great need for studies that specifically examine cognitive tests that can differentiate between MCI and SCD to better mimic the clinical situation (dementia is per definition best identified using Activities of Daily Living scales).
MCI classification
The classification of MCI was based on the results of a comprehensive neuropsychological test-battery and the clinical assessment of a senior neuropsychologist (SV). In borderline cases, a consensus decision was made together with two physicians. The neuropsychological test-battery assessed four cognitive domains: 1) Verbal ability (a multiple-choice vocabulary test, SRB:1, and Category Fluency Condition 2, Delis-Kaplan Executive Function System, D-KEFS) [25, 26]; 2) Episodic memory (Rey Auditory Verbal Learning Test (RAVLT) delayed recall [27] and Rey Complex Figure Test (RCFT) delayed recall) [28]; 3) Visuospatial ability (Block design, WAIS [29] and the copy trial of RCFT) [28]; 4) Attention and Executive functions (the Trail Making Test, Number-Letter Switching, Condition 4 and Verbal Fluency Condition 1, both from D-KEFS) [25]. The test score from each test was compared with published age-scaled normative data and converted to a normative score. The mean z-score from the two tests of each cognitive domain constituted a composite cognitive domain score. Patients with domain z-scores of ≤–1.5 in at least one domain were classified as MCI. In agreement with the DSM-5 criteria for mild neurocognitive disorders, all subjects with composite scores of –1 to –1.5 were individually assessed by the neuropsychologist and classified as MCI if the performance was assessed to represent a significant cognitive decline in comparison with their estimated premorbid level. The MCI classification was then subtyped as amnestic single domain, amnestic multi-domain, non-amnestic single-domain, or non-amnestic multi-domain. All patients with cognitive complaints who did not fulfil the criteria for MCI were classified as having SCD, in agreement with the proposed SCD criteria (that also includes “medical help seeking” which was present for all participants in the present study) [30].
DISCUSSION
In this study, we examined the accuracy of the two most commonly used brief cognitive tests (MMSE and clock drawing test) and a sensitive test of attention and executive function (AQT) for identifying MCI in consecutively included patients seeking medical care due to cognitive symptoms (n = 466). Despite analyzing single tests, optimal combination of tests and multivariable models adjusted for age and education, none of them could differentiate MCI from SCD with adequately high accuracy (a sensitivity and specificity of >80% is usually suggested) [11, 40, 41].
In our opinion, the comparison between MCI and cognitively healthy controls does not warrant clinically relevant diagnostic accuracies. In a clinical situation, where a patient seeks medical help due to cognitive symptoms, the physician needs to be able to differentiate MCI from the more benign condition SCD. Although SCD can be a very early sign of a neurodegenerative disorder, the annual progression rate from SCD to MCI is only 6–7% [44–47], and in community-based populations, the incidence of AD is not significantly higher in SCD compared to healthy controls [48]. On the other hand, for MCI, the annual conversion rate to AD dementia range from 7.5% to 16.5% in clinic-based studies, and from 5.4% to 11.5% in community-based samples [49].
During the recent one to two decades there have been many breakthroughs in AD and dementia diagnostics with CSF analysis of amyloid-β, tau, and neurofilament light, amyloid-β PET, tau PET, and regional atrophy measures from MRI and FDG-PET. However, these diagnostic tools are only available in specialist settings, while primary care still uses the same diagnostic tools as in the late 1970s when the combination of MMSE and CDT was introduced. Our findings as well as other studies show that more novel tests need to replace the MMSE and CDT as the standard screening tests for MCI, especially in primary care [55]. Such newer promising tests should preferably be freely available and may include the Montreal Cognitive Assessment [16, 19, 56], the Memory Alteration Test [57], and sensitive computerized tests [58–60]. Given the possible breakthrough in disease-modifying treatments, where the indication probably will cover MCI and mild dementia but not SCD [14, 61], there is now a great need to focus on improving the diagnostic work-up for identifying MCI.
Supplementary Tables:
Click here for additional data file.(88K, pdf)
