8. Grigoletto F, Zappalà G, Anderson DW, Lebowitz BD.

Norms the elderly with special reference to the early detection of

for the Mini-Mental State Examination in a healthy popula- dementia. Br J Psychiatry 1986;149:698 –709.
tion. Neurology 1999;53:315–320. 11. Brayne C, Gill C, Paykel ES. Cognitive decline in an elderly
9. O’Connor D, Pollitt PA, Brook CP, Reiss BB, Roth M. Practice population—a two wave study of change. Psychol Med 1995;
observed: do general practitioners miss dementia in elderly 25:673– 683.
patients? BMJ 1988;297:1107–1110. 12. Roth M, Huppert FA, Tym E, Mountjoy CQ. CAMDEX. The
10. Roth M, Tym E, Mountjoy CQ, et al. The CAMDEX. A stan- Cambridge Examination for Mental Disorders of the Elderly.
dardised instrument for the diagnosis of mental disorder in Cambridge, UK: Cambridge University Press, 1988.

CME A brief cognitive test battery to

differentiate Alzheimer’s disease and
frontotemporal dementia
P.S. Mathuranath, MD; P.J. Nestor, FRCAP; G.E. Berrios, MD; W. Rakowicz, MBBS; and J.R. Hodges, MD

Article abstract—Objectives: To validate a simple bedside test battery designed to detect mild dementia and differentiate
AD from frontotemporal dementia (FTD). Methods: Addenbrooke’s Cognitive Examination (ACE) is a 100-point test
battery that assesses six cognitive domains. Of 210 new patients attending a memory clinic, 139 fulfilled inclusion criteria
and comprised dementia (n ! 115) and nondementia (n ! 24) groups. The composite and the component scores on the ACE
for the two groups were compared with those of 127 age- and education-matched controls. Norms and the probability
of diagnosing dementia at different prevalence rates were calculated. To evaluate the ACE’s ability to differentiate early
AD from FTD, scores of the cases diagnosed with dementia with a Clinical Dementia Rating ! 1 (AD ! 56, FTD ! 24,
others ! 20) were compared. Results: Two cut-off values for the ACE composite score (88 and 83) were of optimal utility
depending on the target population. The ACE had high reliability, construct validity, and sensitivity (93%, using 88 as
cut-off). Using the lower cut-off of 83, the ACE had a higher sensitivity (82%) and predictive value than the Mini-Mental
State Examination for a wide range of dementia prevalence. The ACE differentiated AD from FTD, and the VLOM ratio
(derived using component scores: [verbal fluency " language]/[orientation " memory]) of #2.2 for FTD and $3.2 for AD
was highly discriminating. Conclusion: The ACE is a brief and reliable bedside instrument for early detection of dementia,
and offers a simple objective index to differentiate AD and FTD in mildly demented patients.
NEUROLOGY 2000;55:1613–1620

The need for screening and diagnostic tests to pro- early and accurate diagnosis, preferably in the pre-
vide an objective measure of cognitive function has dementia stage of the disease3; and 3) the enormous
increased over the last two decades largely as a re- increase in memory clinics, reflecting a growing con-
sult of three developments: 1) the realization that a cern in the general community about failing memory
substantial proportion of patients previously diag- in late life.4
nosed with AD have other pathologies, notably de- Several screening and diagnostic tests for demen-
mentia with Lewy bodies1 and frontotemporal tia have been developed,5,6 but no single test is the
dementia (FTD)2; 2) the advent of disease-modifying established standard.3 More comprehensive cognitive
treatments for AD, making it vital to establish an batteries such as the cognitive section (CAMCOG) of
the Cambridge Examination for Mental Disorders of
the Elderly (CAMDEX)7 and the Dementia Rating
Scale (DRS)8 require specialized test equipment or
Additional material related to this article can be found on the Neurology trained personnel to administer, and are beyond the
Web site. Go to www.neurology.org and scroll down the Table of Con-
tents for the December 12 issue to find the title link for this article.
scope of routine bedside cognitive evaluation. The
Mini-Mental State Examination (MMSE)5 is one of

See also pages 1601, 1609, and 1621

From the University of Cambridge Neurology Unit (Drs. Mathuranath, Nestor, and Hodges, and W. Rakowicz) and Department of Psychiatry (Dr. Berrios),
University of Cambridge, Addenbrooke’s Hospital; and MRC Cognition and Brain Sciences Unit (Dr. Hodges), Cambridge, UK.
Received December 27, 1999. Accepted in final form September 21, 2000.
Address correspondence and reprint requests to Professor John R. Hodges, MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF,
UK; e-mail: john.hodges@mrc-cbu.cam.ac.uk

Copyright © 2000 by AAN Enterprises, Inc. 1613

Downloaded from www.neurology.org by Kathy Pieper on October 26, 2011
the widely used and validated9 bedside instruments The 139 subjects in the clinic group were selected by
for mental status evaluation, but has certain limita- reviewing the case files of the 210 newly evaluated pa-
tions, such as insensitivity to the early stages of AD tients attending the Cambridge Memory Clinic between
when the deficits are confined to an amnestic syn- June 1996 and October 1998. In this multidisciplinary
drome10,11 and to isolated frontal or linguistic deficits clinic patients undergo clinical, radiologic (SPECT scan,
found in early FTD12,13 and inability to differentiate CT, or MRI), and laboratory evaluation. In addition to
the type of dementia. This insensitivity stems from a standard neuropsychiatric and neuropsychological test
lack of measures of executive ability14 and the use of batteries (including the Neuropsychiatric Inventory,19
extremely simple tasks for memory and language Weschler’s Adult Intelligence Scale–Revised,20 Wechsler’s
Memory Scale–Revised,21 Graded Naming Test,22 copying
functions that fail to detect deficits until they are
the Rey Complex Figure,23 and Verbal Fluency Test24) they
advanced.10 Modifications to the MMSE are war-
are also administered the ACE and the Clinical Dementia
ranted and have been attempted.15 Bearing these
Rating (CDR) scale.25 Patients with suspected organic de-
factors in mind, we developed a new, theoretically
mentia syndromes are followed up in the clinic every 6 to
motivated, brief test battery for the detection and 12 months. The diagnosis is based on the consensus of the
classification of dementia based upon our research senior neurologist, psychiatrist, and neuropsychologist in
over the last decade.11-13,16 Addenbrooke’s Cognitive the team using evidence from all clinical and investiga-
Examination (ACE) surveys key aspects of cognition tional results, but not the ACE. Based on postmortem ver-
without the use of specialized test equipment. It is a ification of previously studied samples, our diagnostic
bedside or clinic-based schedule that incorporates accuracy has been high–among 70 cases undergoing au-
the MMSE, expands memory, language, and visuo- topsy between 1992 and 1999, all 30 diagnosed in life with
spatial components, and adds tests of verbal fluency. AD had Alzheimer pathology, sometimes with other sec-
The ACE has been administered over the last 3 ondary pathologies.26
years to all patients referred to the Cambridge Mem- Patients. Of the 210 patients attending the clinic, 139
ory Clinic with cognitive complaints. We describe the fulfilled the following criteria: 1) follow-up of at least 12
psychometric properties and normative values for months; 2) able to complete full assessment; and 3) CDR
the instrument, compare it with the MMSE, and ex- and neuropsychological tests completed within 90 days of
plore its ability to differentiate AD and FTD in a the ACE. Patients were excluded if they had 1) evidence of
group of patients with early dementia. The latter is two or more pathologies (e.g., AD with multiple infarcts on
of particular relevance as a substantial proportion of neuroimaging), either of which could independently be the
younger patients with dementia have FTD and, to cause of dementia; 2) major depression by Diagnostic and
date, simple cognitive batteries have failed to differ- Statistical Manual of Mental Disorders, 4th edition (DSM-
entiate AD from FTD.12,13,17,18 IV)27 or other psychiatric illness; and 3) causes of cognitive
impairment other than degenerative or vascular pathology
Methods. The instrument. The ACE, which can be (e.g., closed head injuries, alcoholism). Of note was the fact
viewed as an Appendix on the Neurology Web site (www. that 51 patients (36%) required a follow-up of 6 to 12
neurology.org), consists of six components evaluating sepa- months before a consensus diagnosis could be reached.
rate cognitive domains. A maximum score of 100 is Patients in the clinic group were classified into demen-
weighted as follows: orientation (10), attention (8), memory tia (n ! 115) or nondementia (n ! 24) groups according to
(35), verbal fluency (14), language (28), and visuospatial DSM-IV.27 For subclassification, the diagnosis of AD (n !
ability (5). The orientation and attention components are 69) was based on National Institute of Neurological and
as in the MMSE. The memory component evaluates epi- Communicative Disorders and Stroke–AD and Related
sodic memory (recall of three items from the MMSE plus a Disorders Association criteria28 and vascular dementia
“name and address learning and delayed recall” test) and (VaD; n ! 14) on National Institute of Neurological Disor-
semantic memory. The language component includes nam- ders and Stroke–Association Internationale pour la Re-
ing 12 line drawings, comprehension, repeating words and cherche et l’Enseignement en Neurosciences criteria.29 In
sentences, reading regular and irregular words, and writ- keeping with our previous studies,12,13,30 the term FTD was
ing. Visuospatial testing consists of copying overlapping used as a general label for all focal lobar degenerations,
pentagons (from the MMSE) plus a wire cube, and drawing which includes patients with core feature of personality
a clock face. Verbal fluency consists of letter fluency for and behavioral changes (frontal variant FTD), nonfluent
words beginning with the letter P and category fluency for spontaneous speech (progressive nonfluent aphasia), and
animals. Raw scores are used for all items except for ver- fluent empty spontaneous speech with semantic break-
bal fluency: a scaled scoring system for the letter and cat- down (semantic dementia). All patients diagnosed with
egory fluency was derived using a Gaussian distribution of FTD (n ! 29) conformed to the consensus criteria.2 Pa-
the raw scores from normal controls included in this study tients who failed to fulfill the criteria for AD, VaD, or FTD
(see the Appendix at www.neurology.org). Scores for each were grouped as others (n ! 27) and consisted of patients
of the six domains can be calculated separately and their with dementia with Lewy bodies, corticobasal degenera-
sum gives the composite score on the ACE. The MMSE tion, or other miscellaneous organic syndromes. The sever-
score can also be calculated. The ACE can be administered ity of dementia was assessed using the CDR grading.25 It is
in 15 to 20 minutes. worth emphasizing that not all patients who fulfilled the
Participants and procedure. The study evaluated the criteria for FTD met the DSM-IV criteria for dementia, as
ACE in 266 subjects consisting of two groups–a clinic impairment in memory, which is a core feature of DSM-IV,
group (n ! 139) and a control group (n ! 127). is often absent in early FTD.12,17
1614 NEUROLOGY 55 December (1 of 2) 2000
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Table 1 Comparison of control, dementia (D), and nondementia (ND) groups on demographics and Addenbrooke’s Cognitive
Examination (ACE) subcomponent, component, and composite mean (SD) scores

Clinic group p Value for D vs:

Characteristics D, n ! 115 ND, n ! 24 Control, n ! 127 ND Control

Demographics
Male sex 61 19 63
Age, y* 66.6 (8.9) 63.8 (7.0) 64.4 (9.3)
Education, y* 11.1 (2.6) 12.7 (3.6) 11.3 (2.6)
ACE (maximum possible score)
Orientation score (10) 7.3 (2.6) 9.8 (0.3) 9.8 (0.3) † †
Attention score (8) 6.0 (2.2) 7.7 (0.5) 7.8 (0.4) † †
Total memory score (35) 17.8 (9.1) 30.3 (3.4) 32.6 (1.9) † †
Name and address learning (21) 13.9 (6.1) 19.4 (1.9) 20.3 (1.0) † †
Name and address delayed recall (7) 1.6 (2.1) 5.5 (1.5) 6.2 (1.0) † †
Verbal fluency (14) 6.3 (3.0) 8.6 (3.2) 11.0 (2.2) † †
Letter P (7) 3.6 (1.9) 4.2 (1.8) 5.4 (1.4) 0.12 †
Category (7) 2.7 (1.6) 4.4 (1.6) 5.5 (1.2) † †
Language (includes naming) (28) 24.1 (4.8) 26.8 (2.5) 27.8 (0.5) ‡ †
Visuospatial (5) 3.1 (1.7) 4.8 (0.4) 4.6 (0.5) † †
Mini-Mental State Examination (30) 21.8 (6.1) 29.8 (5.8) 29.1 (0.8) † †
ACE (composite score) (100) 64.8 (18.9) 88.0 (8.2) 93.8 (3.5) † †

* Kruskal–Wallis test, p $ 0.20.

† p # 0.001, ‡ p # 0.01 (Mann-Whitney U test, two-tailed).

Controls. The control group consisted of 127 age- and nificantly lower scores than the control group on all compo-
education-matched individuals who were either attendees nents and the nondementia group on all except letter
at an orthopaedic (n ! 36) or gynecologic (n ! 28) clinic, fluency.
spouses of the attendees at the above clinics (n ! 26), or Normative data and validity. Two methods were used
members of the Medical Research Council subject panel to calculate the norms for the composite score on the ACE.
(n ! 37). Subjects with a history of head injury, drug The first cut-off score of 88 represented a value two stan-
abuse, alcoholism, and neurologic or cognitive complaints dard deviations below the mean composite score for the
were excluded. control group. The second cut-off was obtained by estimat-
ing the probability of diagnosing dementia (in terms of
Results. Table 1 summarizes the demographic charac- positive [PPV] and negative [NPV] predictive values) in
teristics and mean (SD) individual component and compos- the 139 subjects in the clinic group. We estimated the
ite scores on the ACE for the dementia, nondementia, and sensitivity, specificity, and predictive values for diagnosing
control groups. Age and education were not significantly dementia at different prevalence rates (5, 10, 20, and 40%)
different between the groups. The dementia group had sig- for each ACE cut-off score from 80 to 90. A broad range of

Table 2 Sensitivity and specificity of different ACE (and MMSE) cut-off scores for diagnosing dementia, with corresponding
probabilities of dementia (PPV) at different rates of prevalence

Dementia PPV at different base rates

Test/cut-off score Sensitivity Specificity 5% 10% 20% 40%

ACE
88 0.93 0.71 0.14 (0.99) 0.26 0.44 0.68 (0.94)
83 0.82 0.96 0.51 (0.99) 0.69 0.83 0.93 (0.89)
MMSE
27 0.74 0.96 0.48 (0.99) 0.66 0.82 0.92 (0.85)
24 0.52 0.96 0.40 (0.97) 0.58 0.76 0.89 (0.75)

Figures in parentheses are the corresponding negative predictive values.

ACE ! Addenbrooke’s Cognitive Examination; MMSE ! Mini-Mental State Examination.

December (1 of 2) 2000 NEUROLOGY 55 1615
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 specificity for a large range of sensitivities. A false positive
diagnosis of dementia was made in 7 (5%) patients on
using the higher cut-off on the ACE, and in only 1 (0.7%)
when the lower ACE cut-off (83) or either of the MMSE
cut-off scores were used.
Construct validity. Construct validity evaluates how
well the results of a new test correlate with those of a
standard test for the same domain of interest. Construct
validity for the ACE for diagnosing dementia (as measured
against the DSM-IV) was good (& ! 0.62) using a cut-off
score of 88 and moderate (& ! 0.59) using a cut-off score of
83. The construct validity for the components of the ACE
was evaluated using data from neuropsychological tests
administered to a subgroup of controls, and was good for
the name and address delayed recall (& ! 0.69; against
story recall from Wechsler’s Memory Scale–Revised21) and
verbal fluency (& ! 0.60; against verbal fluency test with
letters F, A, and S24) and moderate for naming line draw-
ings (& ! 0.41; against Graded Naming Test22) and visuo-
spatial component (& ! 0.53; against copying the Rey
Figure 1. Receiver operating characteristics of the Adden- Complex Figure23).
brooke’s Cognitive Examination as a test for dementia. Reliability. Reliability of the ACE was measured in
terms of internal consistency, using Cronbach’s alpha coef-
prevalence rates was chosen to encompass the wide varia- ficient. The Cronbach’s alpha for the ACE was 0.78 ($0.8
tion reported in various clinic31,32 and community-based33,34 is considered excellent and $0.7 good).36
studies. A cut-off of 88 had high sensitivity (93%) at a MMSE versus ACE. Table 3 shows the details of the
specificity of 71% (table 2). A cut-off score of 83 had an type and severity of dementia in cases correctly diagnosed
optimal sensitivity (82%) and specificity (96%), and main- by the MMSE and the ACE. When compared with the
tained a reasonably high PPV and NPV at different preva- lower cut-off score of 83 on the ACE, the MMSE with a
lence rates of dementia. Table 2 also shows the sensitivity, conventional cut-off score of 24 missed dementia in 50% of
specificity, and predictive values for diagnosing dementia FTD cases, 26% of AD cases, and 30% of all dementia
using the MMSE with the conventional cut-off of 24 and a cases. Even at a higher cut-off score of 27, the MMSE still
higher cut-off of 27 for the same sample population. The missed the dementia in 23% of FTD cases. The ACE with
performance of the MMSE, although comparable to the higher cut-off of 88 had the highest sensitivity for detect-
ACE in terms of specificity, was poor in terms of sensitivity ing dementia in the clinic group, including in those with
and predictive values. AD (96%) and FTD (91%).
Criterion validity. The DSM-IV was used as the gold Severity of dementia and the ACE. A correct diagnosis
standard to estimate criterion validity of the ACE (compos- of dementia using the ACE (cut-off score 88) was achieved
ite score) in diagnosing dementia. The trade-off between in 82% of patients with CDR # 1.0, 98% with CDR ! 1.0,
sensitivity (true positive rate) and 1 % specificity (false and 100% with CDR $ 1 (see table 3). Even with the lower
positive rate) of the ACE in diagnosing dementia is shown cut-off score of 83, the ACE diagnosed 79 of the 100 mild or
in the receiver operating characteristics (ROC) curve35 in lesser grades of dementia cases (CDR ! 1), which was
figure 1. The area under the ROC curve is 0.91 (95% CI ! considerably better than either of the MMSE cut-offs. Al-
0.85 to 0.99), which suggests that the ACE has a high most all dementia patients missed by the MMSE (cut-off

Table 3 Numbers (%) of patients correctly diagnosed with dementia on the ACE and the MMSE distributed by their type and severity

Dementia by ACE Dementia by MMSE

Dementia type (n) Cut-off 88 Cut-off 83 Cut-off 27 Cut-off 24

Total (115) 107 (93) 94 (82) 86 (75) 60 (52)

AD (69) 66 (96) 60 (87) 60 (87) 42 (61)
Frontotemporal dementia (22) 20 (91) 17 (77) 12 (54) 6 (27)
Vascular dementia (14) 12 (86) 8 (57) 7 (50) 6 (43)
Others (10) 9 (90) 9 (90) 7 (70) 6 (60)
Severity
CDR # 1 (39) 32 (82) 26 (67) 20 (51) 9 (23)
CDR ! 1 (61) 60 (98) 53 (87) 51 (84) 37 (61)
CDR $ 1 (15) 15 (100) 15 (100) 15 (100) 14 (93)

ACE ! Addenbrooke’s Cognitive Examination; MMSE ! Mini-Mental State Examination; CDR ! Clinical Dementia Rating.
1616 NEUROLOGY 55 December (1 of 2) 2000
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Table 4 Comparison of mean scores on components of the
Addenbrooke’s Cognitive Examination: AD with non-AD and
frontotemporal dementia (FTD) with non-FTD

Components AD, n ! 56 FTD, n ! 24 p Value*

Orientation 7.1 (2.2) 9.0 (1.3)† 0.000

Attention 5.8 (2.0) 7.1 (1.3)† 0.005
Memory Total 16.5 (7.4) 22.3 (7.2)† 0.002
Name and address 13.6 (5.7) 16.0 (4.2) 0.065
learning
Name and address 1.0 (1.7) 3.2 (2.4)† 0.000
delayed recall
Verbal Fluency 6.7 (2.8) 5.5 (3.0) 0.101
Letter 4.0 (1.8)† 2.9 (1.8) 0.012
Category 2.6 (1.5) 2.6 (1.6) 0.987
Figure 3. Bar plot of the VLOM ratio ([verbal fluency "
Language 25.0 (4.0)† 21.8 (5.5) 0.003
language]/[orientation " memory]) against clinical diag-
Naming 10.7 (2.2)† 8.5 (4.0) 0.014 nosis (pink ! frontotemporal dementia, yellow ! AD,
Visuospatial 3.1 (1.7) 3.9 (1.3) 0.066 green ! others) in the study sample.

Values are mean (SD). Bold type indicates significance.

* Mann–Whitney U-test two-tailed significance. 24) but detected by the ACE (cut-off 83) had a CDR ! 1.
† Higher mean score where p # 0.05. The ACE thus maintained a good sensitivity for diagnosing
dementia in subgroups with differing dementia type and
severity.
Differentiating AD and FTD. Of the 139 patients in
the clinic group, the ACE (cut-off score 88) identified 114
as having dementia, of whom 100 (56 AD, 24 FTD, 10 VaD,
and 10 others) had a CDR ! 1. Comparison of the AD and
FTD subgroups on different components of the ACE re-
vealed significant differences on orientation, attention, and
memory, which were worse in AD, and letter fluency, lan-
guage, and naming, which were worse in FTD (table 4).
Figure 2 contrasts the performance of patients with AD
and FTD on the most discriminating subtests. In order to
translate this pattern of scoring into an index useful in
differentiating AD and FTD subgroups, we calculated the
ratio of scores on verbal fluency plus language to orienta-
tion plus name and address delayed recall memory. This
value, (V"L)/(O"M)—the VLOM ratio—tended to be
higher in patients with AD and lower in those with FTD.
For data on the sensitivity, specificity, and predictive val-
ues (at prevalence rates of 10, 20, 30, and 40%) of various
VLOM ratios for differentiating AD from non-AD (and
FTD from non-FTD), please access www.neurology.org. It
is clear that a VLOM ratio of $ 3.2 optimally differentiates
AD from non-AD (sensitivity 75% and specificity 84%), and
a ratio of # 2.2 optimally differentiates FTD from non-FTD
(sensitivity 58% and specificity 97%). Figure 3 shows that
in the patient subgroup with an ACE score #88 and CDR
! 1 the majority with a VLOM ratio below 2.2 had FTD,
whereas above a ratio of 3.2 most had AD. Between 2.2
and 3.2, patients could have FTD, AD, or one of the other
dementias.
The demographic variables of age, years of education,
and gender were added to a logistic regression model as
covariates to determine their effect on the predictive out-
come (dementia or nondementia) obtained using each of
Figure 2. Box plots comparing AD with frontotemporal the instruments—ACE (cut-off scores 88 and 83) and
dementia (FTD) on subcomponents of the Addenbrooke’s MMSE (cut-off scores 24 and 27). Whereas none of these
Cognitive Examination (ACE): (A) verbal (letter) fluency demographic variables was significant at the 0.05 level for
and language; (B) orientation and delayed recall memory. either of the ACE cut-off scores, age (p ! 0.05) and gender
December (1 of 2) 2000 NEUROLOGY 55 1617
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(p ! 0.02) were found to be significant for both the MMSE dementia (CDR ! 1) when they received the ACE.
cut-off scores. When the lower cut-off score of 83 was used, the ACE
detected dementia in 79% of all patients with demen-
Discussion. Extensive experience with the ACE tia, a third more than that achieved using the con-
suggests that it is a reliable instrument for the early ventional cut-off score of 24 on the MMSE. It
detection of dementia and meets most of the stan- appeared particularly sensitive in FTD where it
dards required by such an instrument.3 nearly doubled the detection rate when compared to
How the ACE differs from the MMSE. Since the the MMSE. In a third of all patients with dementia
introduction of the MMSE over two decades ago5 in this study a clinical consensus diagnosis based
there has been an enormous increase in our knowl- upon data from extensive assessments could only be
edge of the dementias and of normal cognition. The reached after a further follow-up of 6 to 12 months.
major differences between the ACE and the MMSE These facts highlight the utility of the ACE in the
lie in the evaluation of memory, fluency, and lan- early diagnosis of dementia.
guage. The memory component of the ACE was ex- Differentiating AD and FTD at an early stage with
panded to reflect the importance of episodic memory the ACE. Predicting the type of dementia that pa-
impairment in the early detection of AD.11,37,38 The tients will eventually develop is often difficult early
name and address delayed recall test appears to be a in the course of the disease. We are unaware of any
particularly sensitive measure in AD. The ACE also other bedside instrument capable of differentiating
incorporates verbal fluency, which relies upon fron- patients at an early stage of dementia. On the ACE,
tal executive function.39 Additionally, letter-based the patients with FTD performed better on tests of
fluency depends upon phonologic processing and orientation and episodic memory, whereas the pa-
category-based fluency on semantic memory.40 tients with AD did relatively better on verbal fluency
Whereas letter-based fluency is particularly sensi- and language, consistent with the known neuropsy-
tive to FTD, category fluency is a marker of semantic chological profiles of the two disorders.12,13,17,47 Based
memory breakdown, including that in AD.41,42 upon this pattern of performance, we devised the
The naming task in the ACE was made more dif- VLOM ratio to differentiate AD and FTD. To illus-
ficult by having 12 line drawings of medium or low trate this point, consider the example of a patient
frequency concept, based on the finding that naming presenting to a typical memory clinic in which the
is highly dependent upon the concept frequency and prevalence rate of AD is around 40% and FTD is
age of acquisition.43 In this study, the AD patients lower, at 10%. If the patient has a VLOM ratio $3.2,
performed well on naming tasks, reflecting their then the probability of AD is 76% and if the ratio is
mild disease. The changes to the nonsemantic as- ! 3.2, then the probability of not having AD is about
pects of language evaluation in the ACE are in- 83%. If the patient’s VLOM ratio is #2.2, then the
tended for early detection of FTD, particularly the probability of FTD is 71% and conversely, if the ratio
progressive aphasic variants.2,13 Changes to the is " 2.2, then FTD can be excluded with 95% cer-
visuospatial section include adding a three- tainty. It is evident that the confidence with which a
dimensional wire cube copying and a clock face diagnosis of AD (or FTD) can be made, or excluded,
drawing test, which have greater scope for detecting depends on the prevalence rate of AD (or FTD) in the
impaired constructional abilities than copying a two- population in question. The predictive values of dif-
dimensional figure.44,45 Both the AD and FTD groups ferent cut-offs for different prevalence rates can be
performed well on this component, reflecting the found at www.neurology.org. Although not infallible,
very mild nature of the dementia in this cohort. an objective and simply calculated index such as the
Psychometric properties of the ACE. The reliabil- VLOM ratio will be helpful in prognosticating and
ity of the ACE is evident in its high internal consis- planning future management of patients.
tency, which indicates that all its component scores Applications of the ACE. When screening an at-
contribute to the measurement of cognitive functions risk population for dementia, a test instrument
and correlate well with the composite score, which in should have a high sensitivity for mild dementia as a
turn determines the presence or absence of demen- missed diagnosis can delay implementation of useful
tia. Among its various components, construct valid- social and pharmacologic interventions. At a specific-
ity was best for memory and verbal fluency showing ity of 71%, a cut-off score of 88 on the ACE offered a
good concordance with standard neuropsychological high sensitivity of 93%. At a dementia prevalence
tests. The ACE also showed good construct validity rate of 40% (such as in a memory clinic) a very high
for the diagnosis of dementia and had a high sensi- proportion (68%) of those who screen positive will
tivity, even with the lower cut-off score of 83. have dementia and 94% of those who score above the
Early diagnosis with the ACE. In the evaluation cut-off will not. The lower cut-off score of 83 might be
of any new instrument, an important question to be more appropriate for research studies or therapeutic
answered is how advanced dementia needs to be be- trials, which require a high specificity, or when
fore the instrument can detect it. To address this screening populations with a low base rate of demen-
issue we used the CDR to grade the severity of de- tia. At a sensitivity of 82%, a cut-off score of 83 had a
mentia in functional terms.46 The majority of pa- high specificity of 96%. In a population with a 10%
tients in this study had only mild or lesser grades of dementia prevalence rate, 69% of those who fail the
1618 NEUROLOGY 55 December (1 of 2) 2000
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test will eventually meet diagnostic criteria for de- diagnostic criteria for senile dementia of Lewy body type. Neu-
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A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal
dementia
P.S. Mathuranath, P.J. Nestor, G.E. Berrios, et al.
Neurology 2000;55;1613-1620
DOI 10.1212/01.wnl.0000434309.85312.19

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