The article reviewed here is ‘Accelerated Clinical Decline in Well-Educated Patients with Frontotemporal Lobar Degenerations’ by Robert Perneczky and colleagues. The authors investigate the effect of education on clinical progression in Frontotemporal Lobar Degeneration (FTLD). The latter part of the abstract for the paper reads:
‘There was a significant positive association between education and CDR-SOB monthly rate of change, indicating a faster decline in the well-educated. Education was the only significant predictor of clinical deterioration‘
On reading the paper, I was thus interested to know what conclusions I could draw with regards to education and clinical progression in Frontotemporal Lobar Degeneration – what was the nature of the relationship described in the last sentence? and how convincing was the association between education and rate of clinical progression. In the introduction, the authors note some of the data on the relationship between higher levels of education and a ‘protective’ effect against dementia which translates into a higher threshold of progression of the underlying pathology before symptomatic manifestation followed by a period of more rapid symptomatic progression. The implication is that cognitive reserve (equivalent to more years of education) increases the threshold for symptom detection (although this may not be the only effect). The question here is obviously more restricted, applying to FTLD.
Turning to the methodology, I wasn’t clear on the sampling procedure. The authors note which department the subjects were recruited from, identify them as being ‘consecutive’ subjects meeting the inclusion criteria although I couldn’t identify these same criteria (or exclusion criteria). Two psychiatrists undertook the clinical examination using the Manchester-Lund criteria supported with the results of relevant clinical investigations which included a neuropsychological battery containing executive/frontal tests. Severity was assessed using the Clinical Dementia Rating Sum of Boxes (German edition). A number of the patients were taking antidepressants and anticholinesterase inhibitors/memantine (which might be expected to influence progression) and so there are already a few important ways in which the sample group is heterogenous (subjects were also stratified according to subtypes of FTLD – FTD behavioural variant, non-fluent progressive aphasia and semantic dementia). The authors also note that the ‘follow-up visit was based on a telephone interview in all patients’. They calculated disease progression as the endpoint CDR severity minus the baseline CDR severity divided by the time interval.
I interpreted the primary hypothesis as being the relationship between years of education and rate of disease progression. The authors note that they use backward and forward regression models and also an ‘exploratory analysis’ of the data which they argue precludes the use of a correction for multiple comparisons.
There were 35 subjects included in the study (22 with FTD, 5 with SD and 8 with NFPA). With regards to the primary outcome measure, years of education versus rate of progression, this data was illustrated in Figure 1 (a scatterplot) in the paper which shows a positive correlation between monthly rate of progression and years of education. Inspecting the scatterplot, it appears that with increasing years of education there is a wider spread of data around the regression line. The p value for the correlation is 0.02. However in terms of clinical significance a change of 0.2 points in the CDR correlated with an additional 9 years of education. A 1 point difference on the CDR for instance is the difference between ‘very mild’ and ‘mild’ severity. So 1/5 of this difference equates roughly to an extra 9 years of education. Nine additional years of education seems like quite a lot of additional education! As the remainder of the analysis was exploratory, I preferred to reserve judgement.
In conclusion, there was a significant correlation between the primary stated outcome of interest – years of education and the progression in clinical severity as measured using the Clinical Dementia Rating Sum of Boxes (German version). However, I thought that the effect size was relatively small. This study provides results which can be used to draw preliminary conclusions about the relationship between clinical progression and years of education in FTLD but as further studies of this nature appear, the possibility of aggregating data in a meta-analysis will become viable.
Perneczky R et al. Accelerated Clinical Decline in Well-Educated Patients with Frontotemporal Lobar Degenerations. Short Communication. Eur Arch Psychiatry Clin Neurosci. 2009. 259. 362-367.
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