Detection of Alzheimer’s Disease and dementia in the preclinical phase: population based cohort study
Palmer, K, Backman, L, Winblad B and Fratiglioni, L;
Commented by , 24 Feb 2003
Aim of the Study
To evaluate a three-step procedure to identify people in the general population in the preclinical phase of dementia.
Method
Subjects were drawn from the Kungsholmen project in Stockholm, a longitudinal study of over 75s.
Assessments
Cognitive impairment was assessed by three tests:
1) A single question : “do you currently have any problems with your memory?”
2) The Folstein Mini-Mental State Examination.
3) Neuropsychological testing of episodic memory, verbal fluency and visuospatial skill; impairment was defined as scoring one standard deviation below the age and education specific means.
Exclusion Criteria
225 participants with established dementia were excluded, as were 31 participants with MMSE < 20 without dementia. Nine people were excluded as their educational background was unknown or they were over 95.
Outcome Measures
The main outcome measure at follow up was presence of Alzheimer’s Disease or dementia, using DSM III-R criteria.
Results
Of 1,435 without dementia, 75 % were female, mean age 81.3 years. At three year follow up, 20 % had died, 12 % refused to participate or had moved, 19 % had developed dementia. Of those who had died, only 6 % had had dementia diagnosed.
When each instrument was used alone, positive predictive values were low, ranging from 25 % for memory complaints to 37 % for recall impairment. Memory complaints had the highest sensitivity, identifying 51 % (44 – 58 % within 95 % confidence interval) of future dementia cases.
Taken together, however, the three-step procedure had a positive predictive value of 85 – 100 % for dementia at three years.
Some people who developed dementia were screened out at each step of the three-stage procedure because of false negative results, arising from the low sensitivity of the instruments.
Discussion
It is already known that no single instrument by itself is suitable for screening for dementia. However, this three-step procedure may be useful in clinical practice for identifying people in the preclinical phase of dementia.
This is clearly an important finding, as treatments for dementia, both drug treatment and social intervention, is likely to be most effective if the illness is caught at an early stage.
Although the positive predictive value is high, the three-step procedure was only able to identify 18 % of those who developed dementia overall, because of the low sensitivity of the three instruments, indicating that there are false negatives at each step. In particular, half the people who developed dementia denied memory complaints three years earlier in the preclinical phase.
The authors speculate that older people regard memory deficits as part of normal ageing and not as medically relevant. Alternative explanations are that they use denial as a defence mechanism, or lack insight into the memory deficit due to subtle organic (frontal) impairment.
Whichever explanation is correct, the authors state that the “challenge for the future is to increase sensitivity at the first step”, which is to get older people to acknowledge and report memory problems early on.