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The article reviewed here is ‘Neuropsychological deficits associated with Alzheimer’s Disease in the very old: Discrepancies in raw vs standardized scores’ (2003) by Bondi and colleagues and freely available here. The other authors include the noted researcher Leon Thal after whom a symposium was named. In the abstract, the conclusion reads
‘These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old‘
The natural question to ask on reading the paper is ‘does the data support the above conclusion?’. From the abstract, the Young-Old are those under the age of 70 and the Very-Old are those over the age of 80 and it can also be seen that while raw scores for both groups are equivalent the age normalised scores produce a different result. Thus when compared with age-matched controls, those over the age of 80 performed significantly better on ‘tests of executive functions, visuospatial skills, and delayed memory’. Thus in the comment above, the ‘disproportionate saliency’ refers to the age-normalised deficits in ‘episodic memory and executive function’ noted in the younger group.
So the first point to make is ‘can we generalise to the ‘Very Old’ and ‘Young Old’ on the basis of this study?’. Looking at the research participants, it can be seen that there are only 33 Young-Old Alzheimer’s Disease patients and 48 Very-Old Alzheimer’s Disease patients. While statistical significance has been reached in the tests, I think this is a relatively small sample size on which to generalise to people in these age groups. Additionally the subjects were participating in a University of California study suggesting that they were likely to be living in California and it can be argued that these results might not necessarily generalise to people living in other areas due to various psychosocial factors. The volunteers who formed the controls were in some cases the spouses of those participating in the study which may suggest a selection bias as spouses may be more likely to be matched in some way – perhaps broadly similar cognitive profiles which would facilitate shared interests although this is conjecture. More importantly, those that were excluded had a ‘history of alcoholism, drug abuse, learning disability, neurologic or severe psychiatric illness’. With increasing age, there is an increasing likelihood of physical illness burden and therefore it can be argued that the controls in this study form a relatively select group who may not necessarily be representative of the age-matched members of the general population.
However it should be noted that in terms of matching, table 1 does show a roughly similar profile between Alzheimer’s Disease patients and controls in terms of age, gender and education suggesting that this is a well-matched control group.
The next question is ‘Can we say that there is a different cognitive profile in the two different age-groups?’. What I noticed here is that in the abstract, the Very-Old and Young-Old groups are described in terms of mean ages (e.g. ‘M age < 70’) while in the methods section they are described in terms of ranges and in table 1 the mean and standard deviation are included. I thought tighter boundaries on the age ranges might have been useful as in the abstract <70 covers a significant proportion of the general population. Moving onto the methodology, subjects were administered a large battery of neuropsychological tests covering a range of functions including amongst others memory, learning and category fluency. In terms of the raw scores, in 14/20 of the tests, the young-old controls outperformed the very-old controls (although not all of these results were significant). On the other hand, in the Alzheimer’s Disease group, the young-old group outperformed the very-old group in only 8/20 of the tests suggesting that there was something different occurring here. In figure 1 they then give the z-scores – this time compared with the age-matched controls.
From this figure, it is possible to see that the executive functions (using modified WCST perseverative errors) appeared disproportionately lower than the scores for the other functions. While other functions showed up as statistically significant on the pairwise comparisons, the executive function had the most significant p-value (p=0.01). However because these were z-scores I wasn’t sure about the clinical significance of these findings. In the discussion, the authors suggest that the relatively poor performance of the very-old control group may have influenced the discrepancy in the cognitive profiles between the two groups on using the standardised scores. They also draw conclusions about the nature of healthy aging when looking at the control groups.
In conclusion, I thought there was a relatively small sample size, that a number of exclusion criteria prevented generalisation to age-matched members of the general population and that a longitudinal design would have provided more convincing evidence of the identified cognitive profile differences. Additionally I wasn’t clear if the executive dysfunction was clinically significant. Regardless of this, the study has produced a useful hypothesis – namely that there is potentially a different cognitive profile in the very-old with Alzheimer’s Disease. Drawing conclusions about ‘healthy aging’ is particularly difficult as for instance a recent study comparing American and British elderly subjects revealed significant differences in age-matched comparisons of cognitive profiles suggesting that ‘healthy aging’ may differ from one population to another. Additionally it is interesting to speculate that executive dysfunction may predispose to an early onset pathology although this would need further testing.
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