Historical perspective

In the last decades of the previous century, interest in diagnosing Alzheimer's disease (AD) was rising. At the same time, MRI was being discovered as an exciting, non-invasive, high resolution method to study brain changes in vivo. Autopsy studies had shown that the medial temporal lobe structures, including the hippocampus, were the structures affected earliest and most severely in AD.1 The first quantitative MRI studies assessing hippocampal volumes in AD described a volume reduction of the hippocampus of up to 40% in AD patients compared with control subjects.2 ,3 Since volumetric analysis of brain structures on MRI scans is a time consuming process which is not routinely available, the need arose to have a more user friendly alternative; a quantitative visual rating scale. In the early 1990s, I had been offered the possibility of doing a six month research fellowship while in my training period of neurology at the Department of Radiology, led by Professor Jaap Valk. At that time my good friend and coworker Frederik Barkhof was working on his thesis on MRI in multiple sclerosis and I did my research on MRI in AD. We sat down and discussed ways to rate hippocampal atrophy but the actual development was done drinking beer and using the beer mat to draw on. We became so enthusiastic that we simultaneously developed a rating scale for white matter changes on MRI, published in 1993.4 From then on, there were two ‘Scheltens’ scales, of which the medial temporal lobe scale has proven to be the most useful.

Although everything is seen in a different perspective 20 years later, and may seem to have lasted shorter than in reality, I still think that it took us probably no longer than 30 min to come up with the definite scale that was ultimately presented in our paper ‘Atrophy of medial temporal lobes on MRI in “probable” AD and normal ageing: diagnostic value and neuropsychological correlates’ in 1992. Before submission, however, we had a meeting with the coworkers, including my friend and colleague Didier Leys from Lille (France), in which we practised the use of the scale and did some inter-rater reliability assessments. At that time it was all done with hard copies and I remember the logistics were quite a challenge. It was probably written in the stars already, but 12 years later, he and I joined forces again as editors of JNNP.

In this paper, one of my first PhD students that worked on the scale, Laura van de Pol, and I, aim to give an overview of the impact this scale had in further research, 20 years after its ‘conception’.

Medial temporal lobe atrophy visual rating scale

The so-called MTA scale (medial temporal lobe atrophy visual rating scale) is based on a visual score of the height of the hippocampus and the width of the surrounding CSF space. The severity of medial temporal lobe atrophy (MTA) is scored from 0 (no atrophy) to 4 (most severe atrophy), originally on one side, and later modified to each side of the brain on a coronal T1 weighted MRI sequence (table 1). The original study showed that MTA scores could distinguish AD patients from control subjects, and further validated the new scale by demonstrating correlations of the MTA scores with linear MRI measurements of the hippocampus and performance on the Mini-Mental State Examination (MMSE)5 and a delayed recall measure. Importantly, the MTA scale proved to be easy to learn and quite reliable, which is expressed by good intra-rater reliability6 as well as fair to good inter-rater reliability, as shown in a study in which four raters rated 100 MRI scans.7

Validation in Alzheimer's disease

The MTA visual rating scale has been further validated against other measurements, in the context of AD over the years. We will address the validation against volumetrics of the hippocampus, neuropsychology and pathology.

Diagnostic tool

Mild cognitive impairment

MCI, as described by Petersen et al,21 refers to non-demented individuals with memory impairment who have an increased risk of developing AD. Longitudinal studies in MCI showed that baseline MTA scores of MCI patients predicted progression to AD. In a group of 190 subjects with MCI, a greater than twofold increase in progression to AD within the next 3 years was observed in subjects with a mean MTA score >2.22

One of the crucial spinoffs of the MTA scale lies within the new research criteria for AD. MTA scoring is incorporated in the algorithm to judge hippocampal atrophy on MRI.23 ,24 For both sets of new criteria, operationalisation and standardisation of MTA scoring is further needed to provide reliable and practical cut-off values.