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Am Fam Physician. 2001;64(3):491-497

Because of the availability of newer agents to treat Alzheimer's disease, it is essential to establish an early and accurate diagnosis. Several tests have been developed to distinguish Alzheimer's from other forms of dementia, especially dementia with Lewy bodies and frontotemporal dementia. None of these tests has become the standard, either because they require specialized equipment and trained personnel or they do not differentiate among the various forms of dementia. The Mini-Mental State Examination (MMSE) is a validated and convenient bedside instrument, but it lacks sensitivity in detecting early stages of Alzheimer's disease and the ability to differentiate types of dementia.

In efforts to overcome these deficiencies, Addenbrooke's Cognitive Examination (ACE) has been developed.

The ACE has been used for more than three years in all patients referred to the Cambridge Memory Clinic to compare it with the MMSE and investigate its ability to distinguish Alzheimer's disease from frontotemporal dementia. The test is a bedside instrument that incorporates the MMSE with additional testing that includes six components to evaluate separate cognitive domains: orientation, attention, memory, verbal fluency, language and visuospatial ability. The test can be given in 15 to 20 minutes. Mathuranath and colleagues investigated ACE in 266 patients divided into two groups: 139 clinic patients and a control group of 127 patients.

Inclusion criteria for patients in the clinic group were new patients registered between June 1996 and October 1998, follow-up of at least 12 months, full assessment (clinical evaluation, brain imaging, laboratory evaluation), neuropsychologic tests (Clinical Dementia Rating) and completion of other dementia tests, including ACE. The diagnoses were based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) and consensus of a team of doctors after review of the test results, except ACE. Exclusion criteria consisted of evidence of two or more pathologic entities contributing to dementia, major depression or other psychiatric illness, and other causes of cognitive impairment. The control group consisted of age- and education-matched control subjects. Patients were excluded if they had a history of head injury, drug abuse, or neurologic or cognitive problems.

Using two cut-off scores, 88 and 83, ACE demonstrated sensitivities of 93 and 82 percent and specificities of 71 and 96 percent, respectively. In comparison, the MMSE had similar specificities but poorer sensitivities. ACE detected dementia in 82 percent of mild cases (determined by their low Clinical Dementia Rating); the MMSE detected only 51 percent of those cases. Thus, the ACE could prove to be a useful bedside instrument to detect early cases of dementia. In terms of distinguishing frontotemporal dementia and Alzheimer's disease, deficiencies in verbal fluency and language were found to be worse in patients with frontotemporal dementia, and deficiencies in orientation and memory were worse in those with Alzheimer's disease. More studies are needed to determine if ACE consistently reflects the same patterns of deficiencies.

editor's note: Because ACE takes longer to perform than the MMSE, it may seem less practical for use in the office setting. However, earlier detection of dementia enables earlier initiation of treatment. Nevertheless, further investigation is required to perfect the instrument, especially because the study population was specialty clinic-based rather than community-based.—s.m.

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