ArticlesProgression to dementia in patients with isolated memory loss
Introduction
Rigorous criteria for diagnosing dementia have been developed and validated.1, 2 Dementia involves impairment of two or more areas of cognition, such as memory, judgment, abstract thinking, and higher cortical function.3 Loss of both short-term and long-term memory in dementia is required in DSM-IIIR criteria.1 There must also be at least one other area of cognitive loss. Similarly, NINCDS-ADRDA criteria for probable Alzheimer's disease require two or more areas of cognitive impairment.2, 3 With the recognition that the initial presentation of dementia may include isolated areas of memory impairment, NINCDS-ADRDA criteria allow a diagnosis of possible Alzheimer's disease in the presence of a single, gradually progressive, severe cognitive deficit.2 Nevertheless, the frequency of patients with isolated memory loss progressing to dementia is poorly understood. Memory loss is often the first symptom of dementia and is often the symptom that leads patients to present4, 5, 6 and what caregivers first notice and become concerned about. In addition, concerns about memory are not infrequent among older adults.4, 7
There are few studies of the natural history of isolated memory loss. Storandt and Hill8 found that memory makes the largest contribution in discriminating mild Alzheimer's disease from healthy ageing. Linn et al9 reported that problems with verbal memory were among the first signs of Alzheimer's disease. These studies do not predict the frequency with which isolated memory loss progresses to dementia. Rubin et al10 reported that 11 of 16 patients with questionable dementia progressed to dementia by 84 months. All seven cases with impairment on the memory subscale of the clinical dementia rating progressed, while only five of nine patients with questionable impairment of memory progressed. Huff et al11 identified 79 patients diagnosed with early Alzheimer's disease based on clinical evidence. Neuropsychological tests in these patients identified no deficits in four, isolated memory loss in six, and single deficits of other cognitive areas in three. Of the seven cases available for follow-up 9–12 months later, three developed multiple cognitive deficits on neuropsychological tests. Tierney et al12 followed up 123 patients who had memory impairment but were not demented. Of these, 29 became demented within 2 years. Measures of delayed recall and attention predicted which patients were likely to progress. Schmand et al13 found that the most powerful predictor of dementia was deficient memory performance. We have investigated progression to dementia in patients with isolated memory loss.
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Participants and methods
We assembled a group of cases having isolated memory loss and another of controls with complaints of cognitive impairment but without dementia or isolated memory loss. Individuals with previously undiagnosed cognitive impairment were identified from a defined portion of a large health-maintenance organisation. 811 consenting individuals with new-onset cognitive impairment were eligible for enrolment in the Alzheimer's disease registry, with a standardised diagnostic evaluation.14
Results
Isolated memory loss was identified in 25 participants. Memory loss was attributable to subarachnoid haemorrhage in one case and alcoholism in another. The cause of memory loss was unknown in the remaining 23. Of these, 21 had 12 months' or more follow-up. The mean age was 73·7 years for cases (range 44–89, first and third quartiles 71 and 77) and 77·5 for the comparison group (41–106, 73 and 78). In cases, 66% (14) were women compared with 59% (117) in the comparison group. 86% (18) of cases
Discussion
Isolated memory loss was uncommon in our series, occurring in only 25 of 811 patients presenting with newly recognised cognitive impairment (3%). In those with isolated memory loss but without an identifiable cause, about half developed dementia within 5 years. This risk was significantly greater than that of persons with newly recognised cognitive complaints who did not have isolated memory loss. Neuropsychological tests at the time of evaluation were not able to identify which patients with
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