"A failing memory may not be the first sign of Alzheimer's disease,” according to the BBC. It reported that a study has found that “spatial skills, such as reading a map or completing a jigsaw, seem to be the first to falter”. Researchers found that these skills appeared to decline sharply up to three years before the disease was diagnosed using current methods.
Behind this report is a retrospective cohort study of more than 400 people, some of whom went on to develop Alzheimer’s disease. Before they were diagnosed, periodic measurements were taken of mental functions including working memory, verbal memory and visuospatial skills. These records identified points in time when Alzheimer’s patients showed rapid declines in these skills that differed from the course of normal ageing.
It is too soon to conclude that this can be used in the diagnosis of Alzheimer’s disease. More research will need to establish whether assessing visuospatial ability improves diagnosis, and specifically how well deteriorating map-reading and jigsaw skills can serve as indicators of the condition.
Where did the story come from?
The research was carried out by Dr David Johnson and colleagues from the University of Kansas and the Washington University School of Medicine. It was funded by the National Institute on Ageing, National Institutes of Health and published in the (peer-reviewed) medical journal Archives of Neurology .
What kind of scientific study was this?
The researchers say that detecting the earliest signs of Alzheimer’s disease is difficult. In this study, they investigated whether there are any evident signs of the disease before the stages at which Alzheimer’s disease is currently clinically diagnosed.
In this retrospective cohort study, researchers examined data from 444 now-deceased volunteers aged between 60 and 101 years. The volunteers were enrolled at the Alzheimer Disease Research Centre between October 1 1979 and December 31 2006. The participants were healthy at the time of their first assessment on enrolment. Before the end of the study in November 2007, all volunteers had at least one additional clinical evaluation.
Clinical assessments involved interviews with the participant and another person, usually the person’s spouse or adult child. A diagnosis of dementia was based on scores on the Clinical Dementia Rating scale, which takes into account the onset of cognitive decline and how it interferes with daily living. Other factors such as health history, medication and neurological examination also contributed to the diagnosis. These assessments took place every year.
In addition, a full set of psychometric tests were given to the patients one or two weeks after their clinical examination. This assessment involved memory and learning tests as well as tests of visuospatial ability (ability to interpret spatial relationships among objects).
Some brains were available for autopsy and samples were also examined to confirm whether dementia was due to Alzheimer’s.
Complex statistical modelling techniques were used to investigate the rate of decline of various measured parameters in people who had progressed to dementia. These included visuospatial ability, working memory, verbal memory and all these factors together. This was done to assess which of these factors changed in advance of the clinical diagnosis of Alzheimer’s disease.
What were the results of the study?
During the course of the study, 310 men (37%) remained stable while 134 (34%) progressed to “uncertain dementia” or Alzheimer’s dementia. Some other men progressed to non-Alzheimer’s dementia (such as vascular dementia), but they were excluded from further analysis and this explains why the percentages above do not add up to 100%.
Overall, those who progressed to dementia had had less education and were older at the beginning of the study. The change in memory and visuospatial abilities that accompanies normal ageing was similar between the two groups until a point where, for those who later went on to develop dementia, there was a rapid decline in these measures. One year before diagnosis, there was a clear decline in working and verbal memory. Two years before diagnosis there was an obvious decline in the global factor (all data taken into account). Three years before diagnosis there was an obvious decline in visuospatial ability.
Similar findings were noted in the subset of 44 people who had their diagnosis of AD confirmed on autopsy, although those with autopsy-confirmed diagnosis had steeper rates of decline in these skills.
What interpretations did the researchers draw from these results?
The authors conclude that their study demonstrates a clear turning point from normal ageing to preclinical Alzheimer’s disease in those who do go on to develop this form of dementia. They say that some of the earliest signs of preclinical disease may occur on tests of visuospatial and speeded psychomotor skills.
What does the NHS Knowledge Service make of this study?
This retrospective cohort study demonstrates the decline in various cognitive skills that precedes a diagnosis of Alzheimer’s disease. Importantly, it shows that visuospatial ability, tested here by established psychometric tests, has a steeper than normal decline three years before existing clinical diagnosis of Alzheimer’s.
There are several important points to consider when interpreting these results:
- Despite what was reported in the newspapers, tasks such as map-reading and proficiency at jigsaws were not explicitly investigated by this study. The participants in this study carried out a series of established psychometric tests in a research environment. It will take more research to understand how well simple tasks in daily life reflect this.
- The study was quite small and limited to a set of people enrolled in a research centre in the US. Its direct relevance to clinical practice and how people are tested and diagnosed for dementia in the UK is unclear.
- Undoubtedly, more research will follow these findings and may lead to the establishment of specific tests that examine visuospatial skills as part of a set of tests that form part of the clinical diagnosis of this disease.
A test that could accurately detect dementia at an earlier stage would be valuable, and more research into this area will follow. At present however, there is not enough evidence that a test of visuospatial skills, or problems with less formal tasks such as completing jigsaws or map-reading, can accurately diagnose or predict Alzheimer’s disease.