Using a large cohort of patients seen in a tertiary memory clinic, we identified four items from the CDR, the current gold-standard informant-based tool for diagnosing dementia, that were most independently predictive of a diagnosis of MCI or dementia and combined these into a screening tool that is easy to remember, easy to administer, and easy to score. The combination of these four items was both sensitive and specific for detecting MCI and dementia in older adults using the gold standard of a diagnosis made by a behavioral neurologist.
The likelihood ratios are robust in both directions. Likelihood ratios are common in medical parlance and allow the users of diagnostic tests to translate the results into clinical meaning for individual patients.17
All test results depend on the pretest probability of the disease in the patient being tested. For screening tests, the pretest probability is simply the prevalence of the disease (which often depends on a few risk factors such as age). Likelihood ratios allow one to convert pretest probability into post-test probability. For example, the pretest probability (prevalence) of dementia in a patient aged 71–79 in the United States is 5%.18
If a patient in this age range tested positive using our screening tool, the likelihood of that patient having MCI or dementia would be increased to 45%. One arrives at this figure by converting the pretest probability into pretest odds (5 ÷ 95 = 0.053), multiplying the pretest odds by the positive likelihood ratio to get the post-test odds (0.053 × 15.6 = 0.82), and then converting the post-test odds to post-test probability (0.82 ÷ (0.82 + 1) = 0.45 = 45%). Conversely if the patient tested negative, the likelihood of MCI or dementia would fall to 0.3%. This would allow a clinician to stratify patients into those who need further evaluation and those who do not.
While informant-based tools can be impractical in some settings, such as when a patient is not accompanied by a caregiver or partner, they have the advantage of lacking the ceiling effect that is common to many performance-based tests for cognitive dysfunction and are therefore much more sensitive for the detection of MCI and early dementia. They are also not influenced by inter-individual characteristics such as level of education. Because early detection is the goal of screening, an informant-based tool such as that presented here is likely to be more powerful than performance-based tests that require a greater level of impairment before they identify an abnormality. It is also possible that a combination of a brief performance-based measurement and an informant interview may prove more effective than ether tool alone.19
This study has several strengths. They include the large cohort in which the screening tool was generated, the variety of dementia subtypes represented, the inclusion of a large number of subjects with MCI and mild dementia, and the ability to validate the findings in a separate, equally robust, cohort. Additionally the screening tool was tested against the current clinical diagnostic gold standard: a thorough multidisciplinary evaluation by a neurologist and neuropsychologist with neuroimaging and laboratory data. The screening tool presented here has similarities to the AD8, a validated eight-item informant based screening tool designed to detect very mild dementia.12
Two of the items in the AD8 were also identified in D=(MC)2
: consistent problems with memory and thinking and difficulty handling complicated financial affairs. Although sensitivity may be sacrificed with D=(MC)2
compared to the longer AD8, its brevity and ease of use may make it more practical in the clinical setting.
Although the test characteristics of this screening tool are promising, several limitations are important to recognize. First, the tool was not developed in the setting in which it would likely be applied. Subjects were all patients referred to a memory clinic; in general such patients or at least their family members have identified a problem leading to referral and therefore the likelihood they would endorse items on the CDR is high. It is possible that when applied in the community among patients whose cognitive impairment is not yet recognized, the questions might be endorsed at a lower rate leading to decreased sensitivity. The population available for study was relatively homogenous, with only a small percentage of Asians and blacks. Our results did not change when the analysis was restricted to whites (data not shown), but there were not enough subjects to compare the results across racial and ethnic groups. Therefore our results may not be generalizable to other ethnicities. Future studies testing the validity of this screening tool should include a more diverse population.
Secondly, the lack of prospective validation is a limitation. The four questions were culled from over 30 CDR questions that were all asked during the course of a structured interview; it is not clear that these four questions would be answered in the same way if asked in isolation. It is also possible that specificity is overestimated because the screening tool was derived from the CDR, which also factors into the ultimate clinical diagnosis. Therefore, subjects who endorse items on the CDR are more likely to be diagnosed with MCI or dementia. This element of circularity could only be eliminated with a prospective validation study in which the four questions identified here are asked independently of the gold standard in the context of an evaluation in a primary care of other non-specialized setting where the tool is likely to be of most practical use. The magnitude of this potential limitation is unclear because the diagnosis of MCI or dementia against which the screening tool was compared was made by a behavioral neurologist after consideration of a large amount of information of which the CDR score is only a minor part: a thorough interview of the patient and collateral source by a physician, a neurologic examination, a complete battery of neuropsychiatric testing, brain imaging, and laboratory analysis. In addition, the diagnosis of MCI also requires poor performance on at least one delayed memory test, so an abnormal CDR (including a score of 0.5) is indicative of impaired function, but does not guarantee a diagnosis of MCI. Prospective validation is a critical step in the development of any screening tool and this must be undertaken before tool presented here can be used clinically. Finally, some items on the CDR could not be included because they were not amenable to dichotomization; it is possible information that could have led to a more robust model was lost as a result.
The four-item informant-based screening tool for MCI and dementia presented here would be simple to administer and easy to remember and score, which would make it practical for everyday use. It is not meant to provide a diagnosis of dementia but merely to identify those at-risk patients who would benefit from referral for a more thorough evaluation. Its performance must be evaluated further in an independent and prospective fashion prior to being adopted for widespread use.