JNNP Online First, published on April 14, 2015 as 10.
1136/jnnp-2014-310090
▸ Additional material is
published online only. To view
please visit the journal online
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1 in clinical practice. By focusing attention on brain
Dementia Research Centre,
University College London
Institute of Neurology,
London, UK
2
Department of Radiology, VU
University Medical Centre,
Amsterdam, The Netherlands
Correspondence to
Lorna Harper, Dementia
Research Centre, University
College London Institute of
Neurology, 8-11 Queen
Square, London WC1N 3BG,
UK; lorna.harper.11@ucl.ac.uk
Received 8 December 2014
Revised 4 February 2015
Accepted 16 February 2015
To cite: Harper L,
Barkhof F, Fox NC, et al.
J Neurol Neurosurg
Psychiatry Published Online
First: [ please include Day
Month Year] doi:10.1136/
jnnp-2014-310090
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
Neurodegeneration
REVIEW
Using visual rating to diagnose dementia:
a critical evaluation of MRI atrophy scales
Lorna Harper,1 Frederik Barkhof,2 Nick C Fox,1 Jonathan M Schott1
ABSTRACT
Visual rating scales, developed to assess atrophy in
patients with cognitive impairment, offer a cost-effective
diagnostic tool that is ideally suited for implementation
regions susceptible to change in dementia and enforcing
structured reporting of these findings, visual rating can
improve the sensitivity, reliability and diagnostic value of
radiological image interpretation. Brain imaging is
recommended in all current diagnostic guidelines relating
to dementia, and recent guidelines have also
recommended the application of medial temporal lobe
atrophy rating. Despite these recommendations, and the
ease with which rating scales can be applied, there is
still relatively low uptake in routine clinical assessments.
Careful consideration of atrophy rating scales is needed
to verify their diagnostic potential and encourage uptake
among clinicians. Determining the added value of
combining scores from visual rating in different brain
regions may also increase the diagnostic value of
these tools.
INTRODUCTION
The diagnostic value of structural neuroimaging is
reflected in its inclusion in the diagnostic guidelines
for a number of dementias, including Alzheimer’s
disease (AD),1 vascular dementia2 and frontotem-
poral dementia (FTD).3 4 Certain imaging features
are suggestive of underlying pathology, such as the
symmetrical and early medial temporal lobe (MTL)
atrophy frequently seen in typical AD, the promin-
ent parietal lobe atrophy associated with early
onset AD, or the asymmetrical atrophy that is often
evident in patients with FTDs,5 and quantification
of these features can enhance their diagnostic
value. Research studies have used a variety of
imaging techniques to help distinguish patients
with dementia from normal control participants, as
well as the more clinically relevant problem of dis-
tinguishing between causes of dementia. However,
volumetric analysis tools and image classifier algo-
rithms, which are commonly used for this purpose,
require specialist software and expertise, are often
time consuming, cannot be applied to all image
types, and are, therefore, seldom used in clinical
practice. Conversely, visual rating scales, principally
developed for research purposes, can be applied
directly to clinically acquired images without the
use of additional software, and with suitable train-
ing, can easily be used as an adjunct to standard
clinical radiology reports.
Visual rating scales focus attention on brain
regions particularly susceptible to change in
Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
specific dementias, most notably the MTLs, and
offer a means of quantifying (on an ordinal scale)
change at the individual patient level. Moreover,
they can be used to enforce structured image
reporting and provide radiologists and non-
radiology clinicians with a framework for inter-
preting imaging findings, making visual assess-
ment more consistent and potentially more
sensitive. However, despite great diagnostic
potential and widespread use in research studies,
visual rating scales have not been widely adopted
into routine clinical practice. In this review, we
examine cerebral atrophy rating scales that have
been developed for use in dementia to highlight
the diagnostic potential of these clinically applic-
able tools. Since MRI is the imaging modality of
choice in dementia, we focus on the scales
designed for this purpose and consider their diag-
nostic utility in terms of the sensitivity and speci-
ficity for disease state, and reproducibility of the
results. As an indication of the impact of each
scale, the number of published studies that have
subsequently applied each scale is provided, as
well an indication of their inclusion in multicentre
studies or clinical trials (table 1). A full descrip-
tion of each scale is included in online supple-
mentary appendix-1.
VISUAL RATING OF GLOBAL CORTICAL
ATROPHY
Scale Pasquier et al12
Increments 4
Display T2-weighted axial
Reliability Inter >0.6, intra >0.7 (Cohen’s κ)
The Pasquier scale, also known as the global cor-
tical atrophy (GCA) scale, was developed to evalu-
ate atrophy in 13 brain regions, including frontal,
parieto-occipital and temporal sulcal dilation and
dilation of the ventricles.11 Regions are assessed
separately in each hemisphere and the final score is
the sum of all scores in the 13 regions. The original
work was used as a tool to quantify atrophy in
patients with stroke, based on the hypothesis that a
greater degree of atrophy is present in patients with
stroke with dementia than in those without demen-
tia. The hypothesis was not validated in the original
paper; however, subsequent studies have demon-
strated that the scale may provide added value as a
composite diagnostic marker for dementia, and in
particular, may be positively associated with vascu-
lar burden.12
1
 Neurodegeneration

Multicentre
Scale O’Donovan et al13
Increments 4

Y10
Display T1-weighted axial
Y7

Y7
N
N
N
N
N

N
N
N
Reliability Inter: 0.9, intra: 0.92 (interclass correlation coefficient)
Trials

As part of study to look at the discriminate power of estab-

Y6

Y8

Y9
N
N
N
N
N

N
N
N
lished visual rating scales for distinguishing between AD and
Applications

dementia with Lewy bodies (DLB), O’Donovan et al13 devel-

Research

oped a rating scale to assess ventricular enlargement (VEn) as a

100+
marker of GCA. Each hemisphere was rated separately for
35

13
12
0
9
3
0
0

0
1
5
enlargement of the lateral ventricles and the scores summed to
get an overall value. VEn scores were found to be significantly
Citations

higher in patients with AD and DLB than in control participants

90/60

21/59
213
350
100 (p<0.003) but similar between patients with AD and DLB.
44

31

19
1

0
0

0
1
Sensitivity and specificity of VEn for AD or DLB versus controls
was 94% and 40%, respectively, and 36% and 74% for AD
0.8/0.79–0.83 (Cκ)

0.83–0.94 (Cwκ)29

versus DLB.
0.93/0.95 (Cwκ)
0.84–0.93 (Uκ)

0.62/0.95 (Uκ)
>0.7 (Cwκ)12

Not reported
Not reported

Not reported
0.75 (Cwκ)
IntraRater

0.92 (ICC)

0.79 (Uκ)
0.8 (Cκ)

Overview of GCA scales

Cwκ, Cohen’s weighted κ; Cκ, Cohen’s κ; Fκ, Fleiss’ κ; ICC, interclass correlation coefficient; KW, Kendall’s W; STIR, short TI inversion time; Uκ, unspecified κ; N, no; Y, yes.
Axial slices provide the best general overview of brain atrophy;
however, specifying regions of interest (ROIs) to quantify such a
large, generalised area is challenging. Using the ventricles pro-
>0.7/0.62–0.71 (Cκ)

0.72–0.84 (Cwκ)29
LAC 0.06 and 0.07

duces excellent reliability; however, sensitivity and specificity

0.65–0.84 (Cwκ)
0.36–0.49 (Fκ)‡
0.75–0.94 (Uκ)

estimates indicate the scale is less useful in terms of differential

>0.6 (Cwκ)12

LAT 0.2 (kw)

Reliability*

0.71 (Cwκ)
InterRater

0.72 (Uκ)†

diagnosis, perhaps due to the considerable variation in ventricu-

0.91 (Uκ)

0.68 (Uκ)
0.64 (Uκ)
0.9 (ICC)

lar size within the healthy individuals. With 13 brain regions,

the Pasquier scale is more extensive in its coverage, although
this comes at the expense of scale reliability, which was further
confounded by the inclusion of regions susceptible to partial
T1-weighted FLAIR

volume effects. Simplification of the Pasquier scale to provide a

MR contrast

T2-weighted

T1-weighted
T1-weighted
T1-weighted
T1-weighted
T1-weighted

T1-weighted
T1-weighted
T1-weighted
T1-weighted

T1-weighted

more general impression of atrophy throughout the brain

(figure 1) resulted in increased uptake among the scientific com-
FLAIR

STIR

munity (table 1); however, the scale has been primarily used as
a component part of a larger diagnostic assessment.12 Owing to
the large brain area assessed by GCA scales, they are likely to be
Coronal Axial Sagittal

more severely confounded by age than other atrophy rating

scales, although their diagnostic value may be improved by
Imaging plane

using age-specific cut-offs.14

Coronal
Coronal
Coronal
Coronal

Coronal
Coronal
Coronal
Coronal
Sagittal

*Highest reported values—citation listed if the value is not taken from the original paper.
Axial

Axial

Axial

Axial

Axial

VISUAL RATING OF FRONTOTEMPORAL ATROPHY

increments

Scale Davies (2013)/Kipps et al17 (modified from Broe et al15)

Increments 5
Scale
Table 1 Reliability measures and imaging parameters

Display T1-weighted coronal

4‡
4

4
5
5
5
5

4
5

5
4
5
4

Reliability: Inter/intra: 0.62/0.82 (frontal), 0.71/0.83 (anterior temporal),

0.64/0.79 (posterior temporal) (Cohen’s κ)
Ventricular enlargement

Davies et al16 devised a scale based on a postmortem staging

Medial temporal
Medial temporal
Medial temporal
Medial temporal
Medial temporal
Medial temporal
Frontotemporal
Frontotemporal
Frontotemporal
Frontotemporal
Global cortical

scheme used to rate atrophy in FTD brains.15 Rating is per-

Brain region

formed at the level of the anterior temporal lobe and the lateral
Posterior

geniculate nucleus, and the highest recorded score is taken

overall (figure 2). The scale was applied to a study population
of patients clinically diagnosed with behavioural variant FTD
(bvFTD), based on the hypothesis that patients with lower
Davies et al16/Kipps et al17

Urs et al33/Duara et al34

atrophy scores have better prognosis and prolonged survival.16

†Based on CT images.
Ambikairajah et al21

‡Novel aspect only.

Favourable prognosis was defined as patients still living inde-

O’Donovan et al13

De Leon et al23 24
Scheltens et al29

pendently 3 years after diagnosis and unfavourable prognosis

Pasquier et al12

Koedam et al38
Kaneko et al35
Galton et al32
Davies et al18

Chow et al22

defined as those who had died or were in institutional care

Kim et al36

within the same time period. Sensitivity and specificity for

Scale

favourable prognosis was 80% and 75%, respectively.

Discriminant analysis also found atrophy to be the sole variable
2 Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090

Figure 1 Example of the four-step (generalised) Pasquier scale for global cortical atrophy.
with significant power to predict prognosis (other variables were
sex, age, symptom duration and various clinical scores).
Kipps et al17 extended this scale further to include rating of
the posterior temporal lobe (figure 2) and described slice selec-
tion in greater detail. The extended scale was applied to a large
group of patients with FTD plus some control participants to
assess the relationship of focal brain atrophy to clinical data. All
control participants were rated <2; therefore, the scale was
dichotomised with scores of 0–1 indicating normal scan appear-
ance and 2–4 indicating a degree of cerebral atrophy. Sensitivity
was 100% for semantic dementia (SD), 73% for progressive
non-fluent aphasia and 53% for bvFTD, based on clinical diag-
nosis of FTD syndrome.
Scale Davies et al18
Increments 5
Display T1-weighted coronal
Reliability Inter: 0.71, intra: 0.76 (Cohen’s weighted κ)
18
Davies et al later developed a more extensive scale, which
included 15 frontotemporal brain regions contained within four
landmark identifiable slices. Specific scale criteria were adopted
in the basal ganglia and hippocampal region (anterior, mid, pos-
terior), and the best slice was determined individually for each
hemisphere to account for variation in brain orientation. The
scale is intended for use in diagnosis and localisation of function
in neurodegenerative diseases and other postoperative or post-
encephalitic brain abnormalities. Discriminant analysis indicated
rating of the anterior fusiform distinguished SD from controls,
while the insula was vital to distinguishing bvFTD. Multiple
regions were reported to be relevant in discriminating AD from
controls (insula, anterior hippocampus, orbitofrontal gyri and
temporal pole), perhaps reflecting the more diffuse pattern of
atrophy associated with AD. In a subsequent study, Hornberger
et al19 reported rating of the orbitofrontal cortex (OFC) as a
good discriminator between AD and bvFTD, with logistic
regression analysis demonstrating correct classification in 71.3%
of patients. Devenney et al20 also used the scale to demonstrate
a lack of atrophy in C9ORF72 mutation carriers.
Scale Ambikairajah et al21
Increments 5 scales all stem from the same postmortem staging scheme, pro-
Display T1-weighted coronal
Reliability Inter: 0.91 (unknown κ)
Ambikairajah et al21 adapted the Davies/Kipps scales16–18 and
applied it to patients on an amyotrophic lateral-sclerosis-FTD
continuum.21 They scored four regions: OFC, anterior cingulate
Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
Neurodegeneration
cortex (ACC), motor cortex and the anterior temporal pole.
Using three landmark identifiable slices, scoring was performed
separately in each hemisphere and then averaged. The study
hypothesis was that there would be a gradient of cortical
atrophy increasing in severity from amyotrophic lateral sclerosis
(ALS) to ALS-FTD to bvFTD, and that patients with ALS and
ALS-FTD would be best distinguished based on atrophy in the
anterior temporal lobe and the ACC. This was partly validated
with bvFTD scoring significantly higher than patients with ALS
in all regions, and ALS-FTD scoring significantly higher than
patients with ALS in all regions except the OFC. Correct classifi-
cation calculated, using a logistic regression model with all
scored regions entered as independent variables, was estimated
to be 83.6% for bvFTD versus ALS and 75% for ALS-FTD
versus ALS. No significant differences in atrophy rating were
found between patients with ALS-FTD and bvFTD with correct
classification calculated as 78.8% between these two groups.
Scale Chow et al22
Increments 5
Display T1-weighted axial, sagittal and coronal
Reliability Inter: 0.06–0.07 (LAC), 0.2 (LAT) (Kendall’s W)
Based on previous findings from volumetric analysis, Chow
et al22 adapted the five-point scale of Davies et al18 to assess
atrophy in the left anterior cingulate (LAC) and left anterior
temporal (LAT) regions. Rating was performed on five slices (2
axial slices, 2 sagittal slices, 1 coronal slice) by four raters. The
scale was applied to a study population of normal controls, AD
participants and participants with a clinical diagnosis of FTD
(FTD diagnosis was not further categorised). Raters were asked
to give a diagnosis immediately after rating. Based on the given
diagnosis, raters averaged 63% accuracy in correctly distinguish-
ing AD from FTD and 59.5% accuracy in distinguishing FTD
from controls.
Overview of frontotemporal atrophy scales
Frontotemporal atrophy scales may be useful in the differential
diagnosis of FTD syndromes, and the scales developed around
these regions have been designed and validated specifically for
this purpose. In particular, the Davies, Kipps and Ambikairajah
viding a reliable basis for region selection. Furthermore, slice
selection is described in detail and reference images provided,
which probably contributes to the consistently high reliability
among these scales (table 1). From a usability perspective, refer-
ence images may be more useful when the ROI is demarcated
with a bounding box as in the Ambikairajah study. The style of
3
 Neurodegeneration
Figure 2 Example of the five-step Kipps/Davies scale for frontal atrophy. The posterior temporal lobe reference images were included in the Kipps
study only.
reference image provided with the second Davies scale, while
informative, is perhaps somewhat complicated for use in routine
practice. From close examination of all reference images, the
spectrum of atrophy represented by each scale is not always uni-
formly distributed between scale increments. In some cases,
such as the anterior temporal region,17 16 the scales may benefit
by condensing the scale to four points rather than five.
Asymmetry in either hemisphere is often associated with FTD5
and can be useful to help distinguish it from other causes of
cognitive impairment; therefore, the decision by Chow et al to
concentrate only on one hemisphere is a potential limitation. In
this study, raters were also encouraged to concentrate on LAC
and LAT regions and ignore hippocampal and parietal atrophy
as atrophy in the latter regions nudged the rater towards a diag-
nosis of AD. This suggests there may be reporting bias, which
could be attributed to improper slice selection; moreover, this
advice may be less appropriate in a non-pathologically con-
firmed study population.
VISUAL RATING OF THE MTL
Scale De Leon et al23 24
Increments 4
Display T1-weighted axial
Reliability Inter: 0.72 (unknown κ)
The De Leon scale, designed to rate hippocampal fissure dila-
tion, was one of the first described imaging markers of AD23
and was subsequently used in a study based on both CT and
MRIs.24 Cross-modality agreement of individual hippocampal
4 Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
rating scale values ranged between ϕ-κ values of 0.87–0.89.
Using a study cohort of patients with AD, patients with mild
cognitive impairment (MCI) and healthy control participants,
this study found sensitivities of 85% for mild AD, 96% for
moderate to severe AD and 78% for MCI, and a specificity of
71% based on the presence of hippocampal atrophy (HA) in the
control participants. They also reported that HA was associated
with increasing ventricular size in all but the mild AD group,
and that increasing HA due to age was confined to the control
group.
Scale Scheltens et al29
Increments 5
Display T1-weighted coronal
Reliability Inter: 0.72–0.84, intra: 0.83–0.94 (Cohen’s weighted κ)
The Scheltens scale focuses on three key features of MTL
atrophy, namely: the width of the choroid fissure, the width of
the temporal horn and the height of the hippocampus25 (figure
3). The degree of atrophy in each of these regions is combined
to produce a score reflecting overall MTL atrophy (see online
supplementary appendix-2). Both sides of the MTL are assessed
separately and in the case of asymmetry the highest score is
reported. In order to assess sensitivity and specificity, the scale is
dichotomised, with scores of 0–1 indicating the absence of AD,
and scores of 2–4 indicating the presence of AD. A sensitivity of
81% and specificity of 67% for AD was reported in the original
study, based on a clinical diagnosis of ‘probable’ AD according
to the 1984 NINCDS-ADRDA criteria26 versus age-matched
control participants. Since it was introduced, the Scheltens scale

has been included in over 100 studies with several reporting
improved sensitivity, specificity and reliability over the original
study, even when used in a clinical setting.27 The reliability of
the scale has been reported to be robust to the clinical experi-
ence of the rater28 but increases as the rater gains more experi-
ence with the scale itself.29 Improved performance of the scale
may be due to advances in image acquisition and display, such
as improved scanner hardware, higher field strengths (the ori-
ginal study was performed at 0.5 T and 0.6 T) and reporting of
the images from digital display over hard copy film images.
Better understanding of the pathological phenomenon measured
by the scale has led to modification of the dichotomised scale to
account for atrophy due to ageing,25 30 which has also helped
to improve performance. The Scheltens scale is included in the
research criteria for the diagnosis of AD.31
Scale Galton et al32
Increments 4 (novel aspect)
Display T1-weighted coronal
Reliability Inter: 0.36–0.49, intra: 0.52–0.69 (Cohen’s κ)
Galton et al32 extended the Scheltens scale to incorporate
non-hippocampal structures. The complete scale is therefore
split into two parts, the first part using the Scheltens scale and
the second part designed to rate the anterior, non-hippocampal
medial ( parahippocampal gyrus) and lateral temporal structures
(see online supplementary appendix-2), each hemisphere was
assessed separately. To assess classification, the complete scale
was dichotomised in to normal or minimal atrophy (0–1) and
moderate or severe atrophy (>1). Eleven per cent of controls
demonstrated atrophy in the hippocampal region but no signifi-
cant atrophy in any other regions. Only in the region of the
hippocampus was atrophy significantly greater in the AD group
than the control group, although only 50% of AD cases had
moderate or severe HA. The SD group showed significantly
greater atrophy in all regions bilaterally. The frontal variant
FTD (fvFTD) group demonstrated significantly greater atrophy
than controls in the temporal poles, hippocampi and right para-
hippocampal gyrus. Significantly greater atrophy in the temporal
pole region and the left parahippocampal gyrus of the SD group
helped to distinguish them from the AD and fvFTD groups.
The SD group demonstrated significantly more atrophy than the
AD group in all regions except the right hippocampus. There
were no significant differences between the AD and fvFTD
groups.
Scale Urs et al33/Duara et al34
Increments 5 coronal images in some centres. The three main ROIs were
Display T1-weighted coronal
Reliability Inter 0.75–0.94, intra: 0.84–0.93 (unknown κ)
Urs et al33 also developed a visual rating system (VRS)
intended to improve on the utility of the Scheltens scale
through better standardisation of the technique and its applica-
tion. However, Duara et al34 published a study applying the
system first and are often credited with its development. The
VRS focuses on a single landmark identifiable slice at the level
of the mamillary bodies (MB). This slice includes the head of
the hippocampus, the entorhinal cortex (ERC) and the peri-
rhinal cortex. Using the VRS software, the MB slice is displayed
along with reference images depicting the five levels of atrophy,
with each of the ROIs outlined to demonstrate the anatomical
boundaries of each of the structures. The study population
Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
Neurodegeneration
consisted of clinically classified patients with AD, patients with
MCI and normal control participants. Based on mean VRS
score, AD participants had significantly ( p<0.05) higher
atrophy rating in all regions compared with normal control par-
ticipants. MCI participants had significantly (p<0.05) greater
atrophy scores in the right hippocampus and ERC bilaterally.
Patients with AD were not distinguishable from patients with
MCI from visual rating scores in any region. Logistic regression
analysis determined that the percentage of correct classification
was 70.2% for MCI versus controls and 72.9% for AD versus
normal controls. Duara et al34 reported sensitivities and specifi-
cities of 71% and 88% for normal controls versus patients with
amnestic MCI, and 81% and 88% for normal controls versus
patients with probable AD.
Scale Kaneko et al35
Increments 4
Display short TI inversion time coronal
Reliability Inter: 0.68, intra: 0.79 (unknown κ)
Kaneko et al35 developed a scale for the evaluation of MTL
atrophy on a single coronal slice in which the cerebral peduncles
appear widest. The scale compares the shape and size of the
hippocampus with the surrounding cerebrospinal fluid (CSF)
space. Perpendicular lines were drawn on both sides of the
hippocampus to divide the CSF space into three parts: an outer
part (temporal horn), an upper part (choroidal fissure) and an
inner part (ambient cistern). Raters were instructed “to put the
hippocampus into each part of CSF space while keeping its ori-
ginal shape and size, as with a jigsaw puzzle piece”. The refer-
ence images demonstrate a hippocampal ROI being manipulated
over the image, but it is not clear from the text if this is simply
to illustrate the point or if this is representative of how the scale
was applied in practice. It is also not clear how the ROI was
generated. Sensitivity and specificity for patients with AD versus
non-demented patients with psychiatric disorders was 88.2%
and 78.9%, respectively.
Scale Kim et al36
Increments 5
Display T1-weighted axial
Reliability Inter: 0.64, intra: 0.62–0.95 (unknown κ)
Kim et al36 adapted the Scheltens scale to rate MTL atrophy
in the axial plane, similar to the older CT-based scale of De
Leon et al.23 The study was motivated by limited acquisition of
transposed from the coronal scale into the axial plane resulting
in rating of: the width of the MTL, the perimesencephalic
cistern gap (measured by the width between the brainstem and
the MTL), and the width of the anterior temporal horn of the
lateral ventricle. By using a score of 2 or above to indicate HA,
the sensitivity and specificity of the scale based on the area
under the curve (AUC) was calculated to be 76% and 80%,
respectively. However, it is not clear what the gold standard
indicator of HA was in this case.
Scale Lye et al37
Increments 4
Display T1-weighted coronal
Reliability Unknown
5
 Neurodegeneration
Figure 3 Example of the five-step
Scheltens scale for medial temporal
atrophy (images from The Radiology
Assistant website—http://www.
radiologyassistant.nl).
Lye et al37 rated hippocampal size on 12 slices through the
hippocampus. Unlike other published scales, a higher score indi-
cates a larger hippocampus. The scale is not described in detail,
although reference images are provided. The scale was used to
investigate the relationship between hippocampal size and
memory performance in people over 80 years of age. It was not
assessed for reliability or sensitivity/specificity for disease state.
Overview of MTL atrophy scales
MTL rating scales were first developed for use with CT imaging
but are now predominantly designed for use with MRI, as the
current imaging modality of choice in the diagnosis of dementia.
The Scheltens scale has had the biggest impact on the field
(table 1), and formed the basis of the Galton and Urs/Duara
scales, which have also been used widely, as well as the recently
developed scale by Kim et al. While the Scheltens scale focuses
on the hippocampus and the surrounding CSF space, the
Galton scale was designed to capture additional information
from the surrounding sulci. However, the between-rater reliabil-
ity of the scale in these regions was poor (table 1), therefore,
limiting the differential diagnostic gain. The software package
used by Urs/Duara helps to operationalise the Scheltens scale by
limiting rating to a single consistent slice and providing detailed
reference information. Adopting this approach provides excel-
lent reliability (table 1) and is well suited to use in research
studies; however, the additional software overhead, and image
preprocessing that is likely to be involved, make it less suitable
to use in clinical practice. Similarly, the Kaneko scale also
appears to use additional software making it impractical for use
clinically; this is further compounded by the decision to validate
the scale on a non-standard MRI pulse sequence. Like the ori-
ginal CT scales, the Kim scale is applied in the axial plane, pro-
viding reasonably good reliability (table 1); however, further
validation of its discriminatory power is required in a clinically
relevant study population.
VISUAL RATING OF POSTERIOR ATROPHY
Scale Koedam et al38
Increments 4 penetrate into clinical practice. We summarise these methodo-
Display T1-weighted sagittal, coronal; T2-FLAIR axial
Reliability Inter: 0.65–0.84, intra: 0.93–0.95 (Cohen’s weighted κ)
The Koedam scale focuses on the posterior cingulate sulcus, pre-
cuneus, parieto-occipital sulcus and the cortex of the parietal
6 Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
lobes.38 The left and right hemispheres are assessed separately
and a separate score is given in each imaging plane. In the case of
different scores in different planes, the highest score is taken. To
assess sensitivity and specificity, the scale was dichotomised with
scores >1 considered an abnormal finding. Based on a study
population of clinically diagnosed late and early onset AD, other
dementias and patients with subjective memory problems
(without cognitive impairment), the sensitivity and specificity of
the scale for AD was 58% and 95%, respectively. In a follow-up
study of postmortem-confirmed dementias, the diagnostic accur-
acy of the posterior atrophy (PA) scale for distinguishing between
the study population groups (AD, frontotemporal lobar degener-
ation (FTLD) controls) based on the average rating between two
raters was assessed by estimating the area under the receiver oper-
ator curve.39 An AUC value of 0.74 was achieved between AD
and control participants, 0.61 between FTLD and controls, and
0.66 between FTLD and AD. To our knowledge, this scale is the
only scale designed to quantify posterior atrophy.
VISUAL RATING DESIGN, METHODOLOGY AND VALIDATION
As table 1 illustrates, several visual rating scales have made little
or no impact, while others have been replicated and cited exten-
sively, with some of the most successful scales also included in
multicentre studies, clinical trials, and as previously mentioned,
the Scheltens’ MTL atrophy scale is also recommended in recent
diagnostic guidelines for AD.31 The methodology employed by
the more successful scales typically focuses not only on estab-
lishing the diagnostic value of the scale in a clinically relevant
population, but also on the test-retest reliability of the scale and
variability between raters. In general, the most successful scales
provide a clear description of the rating procedure, allowing
them to be easily replicated in other studies. Although not dis-
cussed in detail in this review, many studies that employ these
scales demonstrate their correlation with clinical measures of
cognition, adding further validation to their clinical relevance,
and suggesting their potential as a marker of disease severity.
Below we discuss in greater detail a number of factors implicit
in the design of visual rating scales which may determine their
successful adoption in research, and ultimately their ability to
logical considerations and their clinical implications in table 2.
Defining and displaying ROIs
The brain regions selected for visual rating have the greatest
impact on the usefulness of the scale. Regions should be selected

Table 2 Summary of key design decisions, associated methodological considerations and clinical implications
Design decisions Methodological considerations
Defining a region of Is there a good evidence base for atrophy in the region?
interest Should the region be rated in >1 imaging plane?
Is there an imaging landmark to allow consistent slice selection?
Displaying a region of Is the MR contrast appropriate and in common clinical use?
interest Is the appearance of the region badly affected by patient positioning?
Defining scale How much variation can reliably be captured?
increments
Is there a reliable cut-off between normal and abnormal scan appearance?
Should the cut-off be adjusted for age?
Providing training How is each scale increment best described and are there reference images
material available to demonstrate these features?
Are there expert raters available to provide training sets?
Validating the scale What is the inter-rater/intra-rater reliability and how should it be measured?
Do the scores correlate with clinical measures or other measures of atrophy?
Is there a diagnostic gold standard available for comparison?
based on established findings from volumetric image analysis
and/or macroscopic pathological assessment of the disease popu-
lation of interest. The number of regions to be rated, the number
of imaging planes to assess (axial, sagittal or coronal) and the
number of slices used is likely to impact on the reliability of the
scale, with reliability decreasing with increasing scale complexity.
Specifying landmark identifiable slices for rating helps to ensure
consistency between raters. There is good rationale for including
focal regions, such as the MTL, which are typically preferentially
involved in certain conditions, for example, AD, and have been
shown to correlate with clinical measures of disease severity such
as mini mental state examination (MMSE).25 Choice of MR
pulse sequence affects both the appearance of atrophy and the
visible extent of white matter changes and should also be speci-
fied. T1-weighted images offer good grey-white matter and CSF
contrast, with high resolution three-dimensional volume acquisi-
tions (that can be reconstructed in all three planes) offering the
greatest utility for rating atrophy. T2-weighted images are less
reliable, since the amount of CSF can be overestimated if
T2-weighting is too strong. Image quality will also affect the reli-
ability of the scale, with rating less reliable on scans that are
subject to artefacts. Consistent image slice positioning will also
help to improve the reliability of the scale.
Scale increments
The number of scale increments influences the level of detail cap-
tured by the scale. A balance must be struck between detailed quan-
tification and the degree of change that can be reliably differentiated
by visual inspection. In terms of structural neuroimaging, a four-
point or five-point scale is most commonly used. The scale is typic-
ally dichotomised to classify normal and abnormal scan appearance.
In both four-point and five-point scales, scale points 0 and 1 typic-
ally represent the degree of variation within the normal population,
with points 2 and above describing more obvious pathological
change. Four-point scales force the rater to make a more definite
choice of disease state (presence or absence), therefore, increasing
specificity at the expense of sensitivity. Five-point scales on the
other hand may be more sensitive to earlier stages of disease but
may also increase the number of false-positive results. In terms of
the scales developed for use in the diagnosis of dementia, five-point
scales may be particularly sensitive to the effects of ageing. Using
age-specific cut-offs may help to improve scale accuracy.30 40
Harper L, et al. J Neurol Neurosurg Psychiatry 2015;0:1–9. doi:10.1136/jnnp-2014-310090
Neurodegeneration
Clinical implications
Dictates utility and interpretation in certain clinical populations
Requires three-dimensional or multiple image acquisitions and
increases time to perform rating
Improves test-retest reliability
Affects the appearance of atrophy and the sensitivity to artefacts
Difficult to rate certain regions or to reliably assess symmetry if
the head is tilted
Truncated use of the scale may result in decreased diagnostic
value
Affects clinical interpretation
Provides a useful framework for scoring
Provides confidence in ratings and a means of audit
Determines suitability for use in clinical practice and comparison
with other scores
Validates clinical relevance
Provides validation of diagnostic value
The effect of training
Training can have a significant affect on the performance of the
scale. Reference images providing examples of each scale point
are particularly useful and are likely to impact positively on the
reliability of the scale. Reference images which include delinea-
tion of ROIs, such as those provided by Urs et al could also
help to improve reliability, particularly among less experienced
raters or raters without radiology expertise. Detailed descrip-
tions of the expected appearance for each point on the scale can
also be helpful to guide raters and improve consistency. Training
sets representative of the clinical or study population, prerated
by ‘expert’ raters, would help to ensure high observer agreement
before implementation into clinical practice or research proto-
cols. Training sets can also be used to audit rater reliability at
defined intervals or after a period of absence.2
Validation
If rating scales are used as a method of measurement to make
inferences about disease state, it is important that both the
measurement technique and validation of the technique is
rigorous. Test-retest studies are essential to determine the
(inter-rater/intra-rater) reliability of the scale. Appropriate stat-
istical procedures should be applied and fully reported to
allow clear interpretation of the results and fair comparison
with other studies. However, if used routinely, the affect of
training and rater experience is likely to improve the reliability
of the scale. Correlation with clinical measures of cogni-
tion17 25 38 and volumetric measurements18 21 27 41 are also
useful to help validate the scale. Diagnostic tests should also be
validated against an established ‘gold standard’ measurement
technique. Currently, with the exception of individuals with
genetic mutations, postmortem examination of brain tissue is
the only definitive means of establishing diagnosis in neurode-
generative dementia. In most scales described here, classifica-
tion of disease groups, and therefore measures of scale
sensitivity and specificity, are based on clinical diagnosis of the
study population.
CONCLUSION
Visual rating scales have been developed specifically to rate
several brain regions sensitive to atrophy in dementia. They can
be used to provide semiquantitative measures of the degree of
7
 Neurodegeneration
atrophy in these regions, while combining scores from several
rating scales can also improve classification accuracy.39 Unlike
quantitative volumetric measures (manual or automatic), visual
rating scales do not require specialist software or expertise, are
quick to apply and are designed specifically for use with routine
MRI. Moreover, unlike many diagnostic tests, they are not
financially prohibitive, with brain imaging already recom-
mended for all patients being investigated for dementia.1–4
Given the proven utility of some of these scales in clinical
trials,6–9 the relative ease with which they can be applied and, in
the case of the Scheltens MTL score, their incorporation into
new diagnostic criteria,31 it is perhaps surprising that visual
rating scales have not had greater uptake in routine radiological
assessments. Further validation of the real life utility of these
rating scales to improve diagnosis in a multicentre study popula-
tion with postmortem-confirmed diagnosis, combined with the
provision of a widely available training scan set, might help to
transition these potentially useful diagnostic tools into wider use
in routine clinical practice. In addition, clinical studies looking
at the impact of visual rating on diagnosis and patient manage-
ment are also required to determine their true potential as a
diagnostic tool.
SEARCH STRATEGY
References for this review were identified by searches of
PubMed and references from relevant articles. The search terms
‘Dementia’ or ‘Alzheimer’s’, ‘visual rating’, ‘visual assessment’,
‘atrophy rating’, ‘reproducibility’ or ‘rater’, ‘MRI’, ‘magnetic
resonance imaging’, or ‘T1-weighted’ were used. There were no
date or language restrictions. The final reference list was gener-
ated on the basis of relevance to the topics covered in this
review.
Acknowledgements The Dementia Research Centre is an Alzheimer’s Research
UK coordinating centre. The authors acknowledge the support of Alzheimer’s
Research UK, the NIHR Queen Square Dementia Biomedical Research Unit, UCL/H
Biomedical Research Centre, and Leonard Wolfson Experimental Neurology Centre.
LH is supported by funding from Alzheimer’s Research UK and a UCL Impact
Studentship.
Contributors JMS and LH devised the original concept of the article. LH drafted
the manuscript. All authors revised and approved the final version to be published.
Funding University College London.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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