PA is seen in a substantial proportion of AD patients, perhaps particularly in those with an early onset. Because of the complexity of anatomy and variability in posterior regions, this atrophy may be less obvious to inspection than MTA. Moreover, a visual rating scale for PA has been lacking. With this study we aimed to develop a robust visual rating scale, to detect the wide range and complexity of PA. We found that agreement on visual assessment of PA varied between good and excellent. Furthermore, higher PA scores were found in AD compared to controls and other dementias and therefore the scale may be useful in the discrimination between AD and other dementias.
Several studies have shown that the precuneus, parietal lobes and posterior cingulate gyrus are frequently affected in (younger) AD patients and our visual rating scale was designed to include these regions [3, 19, 21–26].
Visual rating of atrophy has shown to be a quick and reproducible method to assess the degree of atrophy in a clinical setting, compared to more labour intensive techniques like volumetric analysis. For applicability in different clinical settings or by different raters, good inter- and intra-rater agreement is essential. Visual rating of MTA using a 5-point scale has become fairly established and has shown fair to good inter-rater agreement [9, 12, 37]. Visual rating of GCA seems harder to perform reliably between different raters, while despite moderate to good intra-rater agreement, poor inter-rater agreement has been reported . Our PA rating scale varied between good and excellent inter- and intra-rater agreement even between raters with different degrees of expertise, suggesting its usefulness in a clinical setting as an aid in assessment of PA. However, degree of agreement was lower for PA compared to MTA (Table 2), which could be due to the fact that visual assessment of MTA is applied for many years in our memory clinic and raters gained much experience. Visual assessment of PA on the contrary has not been done before and our study is the first to assess the applicability of visual assessment of PA in a clinical setting.
MTA is one of the most important markers of AD on MR imaging. In the newly developed AD research criteria, presence of early episodic memory decline and MTA is sufficient for a diagnosis of prodromal AD . MTA, however, has been described in other dementias, which makes MTA by itself less useful in the discrimination of AD from other dementias [13–16, 18]. Furthermore, there is an overlap in hippocampal volumes with normal aging, which could make the interpretation of MTA more difficult in older subjects .
There is increasing evidence that posterior brain regions are relatively more affected in EOAD and medial temporal lobe structures may be less involved [19, 21–24, 26]. Several clinico-pathological studies have reported involvement of the posterior cingulate gyrus, parieto-occipital-, and temporoparietal cortex in AD patients with typical as well as atypical clinical presentations, although the combination with relative sparing of the medial temporal lobe occurs especially in patients presenting without prominent memory impairment [3, 25, 28–30]. PA may be under-recognized, as clinicians may be unaware of this relatively subtle MR imaging characteristic of AD. Our visual assessment of PA was able to discriminate AD from controls and other dementias, whereas MTA failed to discriminate between AD and other dementias. We found that a considerable proportion of AD patients (28%) had prominent PA and mild or absent MTA, whereas only 15% had prominent MTA and mild or absent PA. Furthermore, combining MTA and PA increased the sensitivity for AD. This underlines the importance of evaluating PA in the diagnostic work-up of dementia.
Earlier studies showed that PA was more prominent in younger AD patients [22, 26]. We found that the proportion of patients with predominant PA was higher in EOAD compared to late-onset AD (34% versus 20%). Furthermore, patients with only prominent PA were younger than patients with only prominent MTA, although this difference did not reach statistical significance. However, we did not find a direct relation between PA and age with linear-regression analysis.
A previous study has shown that MTA is correlated with memory deficits and lower MMSE scores in AD . PA seems to have clinical relevance as well, since PA was clearly associated with lower MMSE scores, independent of MTA. This is perhaps not surprising, given the importance of posterior (non-memory) aspects of the MMSE, such as calculation and visuospatial function.
A limitation of our study is lack of pathological confirmation of the diagnoses. We therefore cannot exclude other underlying abnormalities or mixed disease processes. However, all patients were carefully screened and fulfilled clinical criteria for the specific dementia types. It should be noted that our cohort consisted of relatively young AD patients, which could have influenced our results, since PA may be relatively more common in younger patients. Before generalisation of our results to older AD patients, further research is necessary to determine the prevalence of PA in large numbers of young and elderly AD patients and assess its discriminative power and the potential influence of age on its utility.
A considerable number of patients attending a memory clinic are not able to undergo MR imaging for any number of reasons (e.g. pacemaker, limited availability of MR imaging etc.) and computed tomography (CT) could be an alternative. Visual assessment of MTA has found to be comparable on CT and MR imaging and future work should address whether our rating scale is also applicable for CT .
In conclusion this study provides an easy applicable and robust visual rating scale to assess PA. Measurement of PA using this visual rating scale appears to add value in the discrimination of AD from controls and other dementias (FTLD and DLB) on MRI.