Journal of the Neurological Sciences 240 (2006) 7 – 14

www.elsevier.com/locate/jns

Clinical and radiographic subtypes of vascular cognitive impairment in a

clinic-based cohort studyB
Kenneth Rockwood a,*, Sandra E. Black b, Xiaowei Song a, David B. Hogan c, Serge Gauthier d,
Chris MacKnight a, Robert Vandorpe a, Antonio Guzman e, Patrick Montgomery f,
Andrew Kertesz g, Remi W. Bouchard h, Howard Feldman i
a
Dalhousie University, Canada
b
University of Toronto, Canada
c
University of Calgary, Canada
d
McGill University, Canada
e
University of Ottawa, Canada
f
University of Manitoba, Canada
g
University of Western Ontario, Canada
h
Université Laval, Canada
i
University of British Columbia, Canada

Received 25 March 2005; received in revised form 15 July 2005; accepted 22 August 2005
Available online 5 October 2005

Abstract

Background and purpose: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this
paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features.
Methods: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort
consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months.
Results: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n = 97), vascular dementia
(n = 101) and mixed neurodegenerative/vascular dementia (n = 126). Any ischemic lesion on neuroimaging increased the odds (odds
ratio = 9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific
neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and
institutionalization (hazard ratio for combined adverse events = 6.08, p < 0.001).
Conclusions: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however,
are more strongly associated with clinical features than with radiographic ones.
D 2005 Elsevier B.V. All rights reserved.

Keywords: Vascular cognitive impairment; Neuroimaging; Cerebrovascular disease; Index variables; Validation; Subtypes

i
Kenneth Rockwood was the Principal Investigator of the CIVIC study and wrote the first draft of the paper. Xiaowei Song conducted the analyses and
drafted parts of Methods; Robert Vandorpe supervised the neuroimaging and aided in analysis. Chris MacKnight, Serge Gauthier, Antonio Guzman, Patrick
Montgomery, Sandra Black, David B Hogan, Andrew Kertesz, Remi Bouchard and Howard Feldman each led the study at their centres. Each read and
approved the final version of the manuscript and contributed to interim drafts. In addition, Howard Feldman is the principal investigator of A Collaborative
Cohort Of Related Dementias study, conducted in parallel, which gathered and verified initial data from half the sites.
* Corresponding author. Centre for Health Care of the Elderly, 5955 Veterans’ Memorial Lane, Suite 1421, Halifax, Nova Scotia, Canada B3H 2E1. Tel.: +1
902 473 8687; fax: +1 902 473 1050.
E-mail address: kenneth.rockwood@dal.ca (K. Rockwood).

0022-510X/$ - see front matter D 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2005.08.010
8 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14
1. Introduction
From ‘‘arteriosclerotic dementia’’ to ‘‘multi-infarct
dementia’’ to ‘‘vascular dementia’’ to ‘‘vascular cognitive
impairment,’’ to most recently, ‘‘vascular cognitive disor-
der’’ [1,2], the diagnosis of cognitive and functional
impairment seen with cerebrovascular disease continues to
evolve. In contrast to earlier consensus-based approaches
[3,4], future criteria will be more evidence based [2,5,6].
One candidate starting point for new criteria will be
‘‘vascular cognitive impairment’’ (VCI) [7 –10]. Given the
broad conceptualization of VCI, subtypes will need to be
identified if the classification of cognitive impairment in
relation to cerebrovascular disease is to be clinically useful
[7,10 –13].
How to define subtypes is not clear; possible character-
izations include risk factors, mechanisms, pathological
features, radiographic and laboratory characteristics, clinical
features, and/or response to treatment. Three proposed
subtypes are patients with vascular dementia (VaD), those
with vascular dementia in whom a neurodegenerative
dementia also is recognized (i.e., ‘‘mixed’’ neurodegener-
ative/vascular dementia) and those whose cognitive impair-
ment does not meet dementia criteria (i.e., ‘‘vascular
cognitive impairment, no dementia – VCI-ND’’) [14].
Defined clinically, these groups have different outcomes
[15], but further diagnostic refinements that emphasize
neuroimaging have been proposed [11,12]. To help build an
evidence base for clinical and radiographic factors that
might aid in subtyping VCI, we report data from the
Consortium to Investigate Vascular Impairment of Cogni-
tion (CIVIC) study [16].
The CIVIC study’s general aim is to empirically test the
various sets of consensus-based criteria [9] by evaluating
how VCI is diagnosed. It is important to recognize that this
study observed how VCI was diagnosed, rather than
prescribed how it should be diagnosed. In short, rather than
develop yet another set of consensus criteria, we recognized
that dementia specialists diagnosed VCI in practice. Thus, the
CIVIC study investigated which of the features from
consensus-based criteria practicing dementia specialists
actually used. Here, our objective is to test the predictive
validity of VCI subtypes. The rationale for focusing on
predictive validity is that while the historical referent criterion
(the so-called ‘‘gold standard’’ of neuropathology) has lost
some of its lustre [12,17,18], the prediction of relevant, non-
arbitrary outcomes still enables clinicians to understand the
criterion validity of any proposed classification scheme.
2. Methods
Following the methods and terminology of Streiner and
Norman [19], we evaluated the validity of subtypes by first
understanding whether patients looked recognizably differ-
ent from each other (construct validity) and then contrasted
their outcomes (predictive/criterion validity). We compared
characteristics across VCI subtypes to patients with no
cognitive impairment (n = 151; note that these people had
presented with memory complaints and were not normal
volunteers) to those with vascular cognitive impairment, no
dementia (VCI-ND, n = 253), that was not of a vascular
cause (chiefly, these patients had mild cognitive impair-
ment) or to those with probable AD, diagnosed using
standard criteria that excluded mixed AD/VaD [20]. To
evaluate predictive validity, we compared rates of death and
institutionalization.
As detailed elsewhere [16], CIVIC enrolled 1347 patients
from 9 Canadian memory clinics. In general, dementia and
AD were diagnosed using standard criteria [20,21]. VCI was
diagnosed in 324 people (24%). We built on usual care, to
which was added a clinical report form. The report form
incorporated every unique item from the standard criteria
[20,21], the Hachinski Ischemia score [22] and the National
Institute of Neurological Disorders and Stroke/Association
Internationale pour la Recherche et l’Enseignement en
Neurosciences [4], Alzheimer’s Disease Treatment Centers
of California [3] and International Classification of Disease,
10th edition [23] criteria. In this way, we were able both to
see how many patients met each set of criteria (as reported
earlier [16]) and to evaluate which items were most often
recorded when a VCI diagnosis was made. In a separate
report, we will evaluate each individual criterion; here, we
take the necessary first step of presenting data on the major
subtypes that have been proposed for clinical and imaging
evaluation.
In addition to recording data on all VaD criteria, we
completed the Disability Assessment for Dementia [24], the
Mini-Mental State Examination [25,26], the Functional
Assessment Staging Tool [27], the Functional Rating Scale
[28] and the Cumulative Illness Rating Scale [29]. In all
scores save the Mini-Mental State Examination and
Disability Assessment for Dementia, a higher score means
worse performance. The CIVIC protocol paralleled those of
the Canadian Study of Health and Aging [30] and A
Collaborative Cohort of Related Dementias [31]. The
checklist and initial clinical classification have proved to
be reliable [32].
Neuropsychological testing and neuroimaging were
obtained at the discretion of the examining physician. As
we built on usual care, we had no standard protocol for the
actual imaging acquisition but employed a guide for the
interpretation of CT and MRI (available upon request) for
scans that were recorded during initial assessments or in the
previous 3 months. The interpretation guidelines were based
on those used in the Stroke Data Bank [33] and the Dutch
TIA Study [34,35] Here, we report CT data only (n = 779, of
whom 691 had either no cognitive impairment, non-vascular
cognitive impairment without dementia, VCI, or AD; total
n = 1191).
The CIVIC protocol required regular follow-up over 30
months, either in clinic (where the original assessments
 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14 9

Table 1
Baseline characteristics of patients with different VCI subtypes, AD, non-vascular CIND, and NCI
No cognitive Non-vascular cognitive Vascular cognitive Vascular Alzheimer’s Alzheimer’s F, v 2 p
impairment impairment, impairment, dementia disease/vascular disease
no dementia no dementia dementia
n = 151 n = 253 n = 97 n = 101 n = 126 n = 463
Age mean (S.D.) 62.9 (12.8) 68.5 (12.0) 72.8 (9.9) 75.4 (8.1) 78.0 (6.7) 75.6 (7.9) 57.4 <0.001
Female n (%) 91 (60.3) 140 (55.3) 48 (49.5) 36 (35.6) 63 (50.0) 298 (64.4) 34.7 <0.001
Education mean (S.D.) 12.6 (3.4) 12.1 (4.4) 10.6 (3.6) 11.2 (3.7) 11.0 (4.0) 11.0 (3.8) 6.3 <0.001
Hypertension n (%) 49 (32.5) 85 (33.6) 54 (55.7) 57 (56.4) 68 (54.0) 143 (30.9) 55.8 <0.001
Diabetes n (%) 15 (9.9) 29 (11.5) 28 (28.9) 19 (18.8) 21 (16.7) 35 (7.6) 43.2 <0.001
Dyslipidemis n (%) 33 (21.9) 44 (17.4) 27 (27.8) 21 (20.8) 19 (15.1) 59 (12.7) 17.6 0.003
Mini-Mental Score 28.6 (1.9) 26.1 (3.8) 25.9 (3.2) 21.5 (5.6) 19.0 (6.1) 19.1 (6.3) 127.1 <0.001
Examination mean (S.D.)
Functional Rating 10.6 (2.6) 14.6 (4.6) 14.8 (4.2) 23.4 (6.4) 24.7 (6.2) 23.3 (6.9) 193.8 <0.001
Scale mean (S.D.)
Disability Assessment for 37.4 (4.7) 33.2 (8.0) 32.0 (7.3) 24.8 (10.2) 24.7 (9.3) 26.5 (9.5) 37.1 <0.001
Dementia mean (S.D.)

were repeated) or by a telephone interview (which included
the informant-based Disability Assessment for Dementia
and the Informant Questionnaire on Cognitive Decline in
the Elderly [36].) The Canadian Study of Health and Aging
decedent interview [37] was used to assess pre-morbid
progression of cognitive and functional impairment in
patients who had died.
In the analysis of construct validity, we first compared
demographic and clinical features (including those from
the history) between VCI and other diagnoses and within
VCI subtypes. Comparisons were made between individ-
uals with NCI, AD, non-vascular cognitive impairment
without dementia and the VCI subtypes of VCI-ND, VaD
and mixed AD/VaD. To evaluate risks associated with
VCI, the comparator group was no cognitive impairment,
as the logic is to define a disease entity. We compared
VCI subtypes with AD, as the logic is to define a new
entity amongst people with cognitive impairment. Base-
line intra-group variation was investigated using v 2 and
ANOVA.
In the evaluation of predictive validity, we used the log-
rank test to assess differences in time-dependent outcomes
between diagnostic groups. For multivariable modeling of
time-dependent outcomes, the assumption of proportional
hazards was tested and, if verified, was used to evaluate
differences in survival times to death and time to institu-
tionalization, portrayed with Kaplan –Meier curves.
In the evaluation of both construct and criterion validity,
we were obliged to consider a large number of variables that
might define subtypes. Recognizing the power required to
evaluate so many factors, dimensionality reduction was
achieved in several ways. In addition to multivariable
modeling, we combined 20 vascular risk factors (e.g.,
hypertension, diabetes, dyslipidemia) in a vascular risk
factor index variable and 17 clinical features in a vascular
clinical profile index variable, as described elsewhere [38].
The clinical index included acute onset, fluctuating course,
periods of prolonged plateaus, memory impairment not the
main complaint, focal symptoms, frequent falls, an early
gait abnormality, early urinary incontinence, pseudobulbar

Table 2
Vascular profiles of patients with different VCI subtypes, AD, non-vascular CIND, and NCI
Number of No cognitive Non-vascular cognitive Vascular cognitive Vascular Alzheimer’s Alzheimer’s v2 p
present (%) impairment impairment, impairment, dementia disease/vascular disease
no dementia no dementia dementia
n = 151 n = 253 n = 97 n = 101 n = 126 n = 463
Acute onset 1 (0.7) 3 (1.2) 13 (13.4) 18 (17.8) 5 (4.0) 4 (0.9) 63.1 <0.001
Stepwise progression 0 0 3 (3.1) 12 (11.9) 6 (4.8) 1 (0.0) 40.6 <0.001
Fluctuating course 0 4 (1.6) 8 (8.2) 11 (10.9) 5 (4.0) 5 (1.1) 26.1 <0.001
Nocturnal confusion 0 3 (1.2) 3 (3.1) 12 (11.9) 20 (15.9) 17 (3.7) 30.1 <0.001
Gait abnormality 1 (0.7) 12 (4.8) 14 (14.4) 28 (27.7) 14 (11.1) 15 (3.2) 26.2 <0.001
Urinary frequency 1 (0.7) 8 (3.2) 12 (12.4) 22 (21.8) 16 (12.7) 19 (4.1) 14.4 0.013
History of falls 3 (2.0) 19 (7.5) 18 (18.6) 30 (29.7) 16 (12.7) 21 (4.5) 21.0 0.001
Personality changes 5 (3.3) 28 (11.1) 19 (19.6) 31 (30.7) 24 (19.0) 71 (15.3) 4.4 0.498
Mood changes 8 (5.3) 40 (15.8) 26 (26.8) 29 (28.7) 25 (19.8) 66 (14.3) 11.9 0.037
Emotional incontinence 0 2 (0.8) 5 (5.2) 10 (9.9) 6 (4.8) 7 (1.5) 9.1 0.106
Somatic complaints 6 (4.0) 4 (1.6) 2 (2.1) 3 (3.0) 3 (2.4) 7 (1.5) 36.4 <0.001
Psychomotor retardation 2 (1. 3) 3 (1.2) 2 (2.1) 12 (11.9) 7 (5.6) 8 (1.7) 11.6 0.041
10 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14

Table 3
Radiographic neuroimaging lesion profiles of patients with different VCI subtypes, AD, non-vascular CIND, and NCI
Number of No cognitive Non-vascular Vascular cognitive Vascular Alzheimer’s Alzheimer’s Total
present (%) impairment cognitive impairment, impairment, dementia disease/vascular disease
no dementia no dementia dementia
n = 37 n = 133 n = 77 n = 87 n = 99 n = 258 n = 691
Cortical 2 (5.4) 0 18 (23.4) 17 (19.5) 15 (15.2) 5 (1.9) 57 (8.2)
Subcortical 3 (8.1) 3 (2.3) 8 (10.4) 19 (21.8) 13 (13.1) 11 (4.3) 57 (8.2)
White matter 8 (21.6) 36 (27.1) 22 (28.6) 23 (26.4) 32 (32.3) 86 (33.3) 207 (30.0)
Cortical and white matter 0 0 3 (3.9) 7 (8.1) 2 (2.0) 0 12 (1.7)
Cortical and subcortical 0 0 1 (1.3) 3 (3.5) 5 (5.1) 0 9 (1.3)
Subcortical and white matter 1 (2.7) 0 9 (11.7) 8 (9.2) 13 (13.1) 1 (0.4) 32 (4.6)
Other intracranial lesions 4 (10.8) 12 (9.0) 4 (5.2) 1 (1.2) 6 (6.1) 17 (6.6) 44 (6.4)
All of these types 0 0 0 0 0 1 1 (0.1)
None of these types 19 (51.4) 82 (61.7) 12 (15.6) 9 (10.3) 12 (12.1) 138 (53.5) 272 (39.4)

palsy, low mood and patchy cognitive deficits. The index
variables are each scaled as unweighted proportions (e.g., in
the 17-item clinical index, a patient with 4 items would have
an index score of 4/17 = 0.24). As reported elsewhere, the
shape and scale parameters of their distributions suggest that
the index variables operate validly as state variables; their
observed ranges were 0 –0.58 and 0– 0.65 [38].
Each index was evaluated in multivariable models. Final
models to define subtypes were based on both statistical and
clinical criteria. For example, factors not available at
baseline, (e.g., progression of impairment) or not routinely
available (e.g., MRI) or that while traditional criteria were
similar to each other, and to patients with AD, than to
patients with no cognitive impairment (Table 1). More VCI
patients were men and were generally more likely to have
vascular risk factors. VCI patients differed from patients
with AD, and between each other, by clinical subtypes.
Of the clinical features, acute onset, gait abnormalities,
falls and urinary abnormalities were most associated with a
VCI diagnosis. These remain associated with VCI in models
adjusted for age, sex and degree of severity (Table 2).
(A)
1.00 NCI
Survival function estimate

little used by clinicians (e.g., ‘‘preservation of personality’’),

were not entered in the final model. In addition, as vascular 0.95
risk factors are recognized as risks for AD [39], the risk
0.90 AD
factor index variable was not included in the logistic
regression model for assessments of subtypes, where AD
0.85
patients formed the comparator group. By contrast, given
NCI (n=151)
their status as risk factors for impaired cognition [40], the 0.80 Vasc. CIND (n=151)
vascular risk factor index variable was included in the VaD (n=101)
Ad/VaD (n=101)
model for VCI, in which NCI patients formed the 0.75 Ad (n=463)
comparator group.
0 10 20 30
Time to death (months)
3. Results
(B)
In evaluating whether subtypes are recognizably distinct, 1.00
Survival function estimate

we first note that the 324 patients with VCI were more NCI
0.95
Table 4
Factors associated with a diagnosis of vascular cognitive impairment 0.90
compared with no cognitive impairment in a multivariable logistic
regression analysis 0.85 AD
Odds ratio (95% CI) Wald Sig
Age 1.02 (0.99 – 1.04) 2.507 0.113
0.80
Sex 0.53 (0.37 – 0.76) 11.937 0.001
Years of education 0.99 (0.94 – 1.03) 0.308 0.579 0.75
MMSE 1.05 (1.02 – 1.08) 9.386 0.002 0 10 20 30
Risk index 1.07 (1.05 – 1.09) 44.919 <0.001
Clinical index 1.06 (1.04 – 1.08) 51.568 <0.001 Time to institutionalization (months)
Lesion 9.20 (6.39 – 13.23) 142.984 <0.001 Fig. 1. Survival curves for mortality (Panel A) and institutionalization
Constant 0.007 29.561 <0.001
(Panel B) by clinico-radiographic subtype.
 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14 11

Neuroimaging profiles show modest but statistically sig-
nificant differences across diagnostic categories (Table 3),
although within VCI subtypes, the distributions of lesions
were similar.
In models of factors associated with a diagnosis of VCI,
several features were important, including, most obviously,
measures of the degree of cognitive and functional impair-
ment (Table 4). For example, every 1-point decrement from
30 in the MMSE increased the odds of a VCI-ND diagnosis
by 1.05 (95% confidence interval 1.02 –1.08). Every 1-point
change in the vascular risk index profile showed a similarly
increased likelihood (1.07; 1.05– 1.09) as did a 1-point
increase in the clinical index variable (1.06; 1.04– 1.08). An
ischemic lesion, particularly stroke detected by neuroimag-
ing, increased the risk by 5.21 (2.96 – 7.45) when other
factors are controlled. Similar profiles of vascular risks,
vascular clinical features and ischemic neuroimaging lesions
increased the risk for the subtypes of vascular dementia and
mixed dementia. Cortical or subcortical stroke, rather than
white matter changes, increased the odds of a VCI
diagnosis.
Both clinical and imaging subtypes were associated with
adverse outcomes (Figs. 1 and 2). All cognitively impaired
(A)
1.00
Survival function estimate
patients had higher rates (cf. no cognitive impairment) of
death and institutionalization (log-rank test = 33.3, P <
0.001). People with the subtypes VaD and mixed dementia
had higher 30-month rates of adverse outcomes. By
contrast, even compared to people with no cognitive
impairment and no imaged lesions, no single type of
neuroimaging lesion conveyed a worse prognosis. For
example, of the 207 patients with white matter lesions, 21
were institutionalized and 17 died (total adverse event rate
18%), compared with 30 (24%) adverse outcomes (includ-
ing 12 deaths) amongst the 123 with ischemic lesions
without white matter involvement and 6 (18%) adverse
events amongst those with VCI but no imaged lesion (log-
rank test = 0.09, p = 0.95), A similar result is obtained for
institutionalization. (Note that the survival estimates cross
over the full time interval, so that the assumption of
proportionality of hazards is violated and, hence, the
presentation only of unadjusted estimates.)
4. Discussion
In a multi-centre, Canadian memory clinic-based study,
we found that both clinical features and radiographic
features helped to establish a diagnosis of VCI, selecting
patients who were recognizably different from those with no

cognitive impairment and with AD. Both clinical and

0.95
radiographic features also allowed VCI subtypes to be
defined, but the outcomes of patients with differing VCI
0.90 subtypes were more strongly associated with clinical
features than with radiographic ones. Given that VCI is
0.85 common [15], costly [41] and perhaps susceptible to
No leision (n=33) treatment or even prevention [39,42], our finding that it
0.80 No white matter leision (n=110) can be readily classified and pragmatically sub-classified
Any white matter leision (n=120)
can help to establish a framework for future studies. Such
0.75 sub-classification is needed, given that VCI is broadly
0 10 20 30
3
Time to death (months)
constituted and that sub-groups of clinically identifiable
patients might usefully guide diagnosis and management.
(B) Our data must be interpreted with caution. Estimates
1.00
derived from memory clinics will differ from estimates
Survival function estimate

0.95 derived from stroke clinics [6]. This does not mean that they
will be unimportant, however, especially if VCI without
clinically evident stroke is more common than VCI with
0.90
stroke [11,15].
0.85 The most important limitation, however, is the absence of
a study-specific neuroimaging protocol for all patients. In
0.80
particular, of the 1191 patients whom we considered as VCI,
no cognitive impairment, non-vascular cognitive impair-
ment without dementia or AD, only 691 (58%) had relevant
0.75
0 10 20 30 neuroimaging within 3 months of the initial clinic visit.
Time to institutionalization (months) Selection for imaging was biased towards VCI (81% of
whom had CTs) compared with no cognitive impairment
Fig. 2. Kaplan – Meier survival estimates of the time to death (Panel A) and
(25%), non-vascular CIND (53%) or AD (56%). On the
institutionalization (Panel B) amongst patients with vascular cognitive
impairment, by imaging subtype (here grouped as any lesion with white other hand, the numbers of scans that we considered are
matter involvement, any lesion without white matter involvement, and no substantial enough that strong signals should be readily
imaged lesion). detected. Moreover, the impact of imaging recruitment bias
12 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14
would be to over-estimate the number of people with
lesions, as well as their impact. Thus, our estimate that, even
amongst imaged patients, an important minority with
clinically diagnosed VCI did not have CT neuroimaging
evidence of an ischemic lesion is a conservative one.
Importantly, too, in the unadjusted analyses, this profile
conferred a poor prognosis.
How to interpret a ‘‘clinical VCI/no CT-imaged lesion’’
subclass is unclear. On the one hand, it might simply
represent falsely negative neuroimaging, inasmuch as
routine MRI might have shown important ischemic lesions
not evident on CT [43]. On the other hand, while CT/MRI
helps to validate the clinical diagnosis, it is clear that
clinically important ischemic lesions can exist which are not
well correlated with available neuroimaging [44] (i.e., that
there are problems of specificity—also evident in the
observation that MRI-defined white matter changes are
common in all types of VaD) [45]. Additionally, there are
problems of sensitivity—the radiological portion of VaD
diagnostic criteria now exclude bona fide cases of VaD [46].
Similarly, although neuropsychological testing occurred at
each site, it was ordered variably and included variable tests,
so that standard neuropsychological data cannot be reported
for all VCI patients.
Against this background, it should not be surprising
that both clinical and neuroimaging features are important
to a VCI diagnosis. Consider too that even in post-stroke
cohorts, both imaging (CT) and clinical features are
important in predicting dementia [47]. Moreover, although
there is clearly room for methodological improvement in
many of the studies that have not discerned a specific
relationship between lesions and cognitive deficits [48],
even longitudinal studies have not always been able to
disentangle the associations between the neuroimaging
and the cognitive deficit [49]. In this context, our
pragmatic clinical focus suggests that while the neuro-
imaged lesion conveys information helpful to a VCI
diagnosis, additional data are needed to understand
prognosis. While it might be that more sensitive modal-
ities, including indices of cerebral metabolism which
might have a better yield, some of the claims made for
advanced imaging techniques are faltering. For example,
the distinction between periventricular white matter hyper-
intensities and deep ones has been found to be less
helpful than considering total WMH volume relationships
[50]. Other recent studies have undermined the extent of
the specificity of localized MRI-detectable lesions in the
presentation of dementia. For example, regardless of
where in the brain white matter hyperintensities are
located, they have been found to be associated with
frontal hypometabolism and executive dysfunction [51]. In
addition, the neuroimaging component of the National
Institute of Neurological Disorders and Stroke/Association
Internationale pour la Recherche et l’Enseignement en
Neurosciences criteria does not distinguish between older
patients with and without post-stroke dementia [52]. Thus,
while better imaging might have transformative effects, it
is also important to assess what might be done in the
meantime, especially outside large academic centres, and
in non-Western countries, where CT might be the best
that is routinely available [53].
How to understand neuroimaging illustrates a more
general problem that has proved to be difficult in developing
VCI criteria, in that single factors can operate as both
exposures and outcomes. For example, white matter
changes are common in all dementia types examined—
and not rare in older people without cognitive impairment
[54]. White matter changes are importantly related to
disease exposures (e.g., hypertension) and in this sense
operate as an outcome. In addition, however, they are a risk
factor for adverse outcomes (e.g., impaired cognition) and
thus also operate as an exposure [55 – 58]. The need not to
include vascular risk factors as criteria for VCI is well
recognized, but these data call attention to how circularity
might be avoided with respect to neuroimaging. This must
be addressed forthrightly, as new neuroimaging techniques
are being developed against a background of questioning
the role of neuropathology [18]. The frequent disagreement
between differing neuropathological criteria [59], the
number of people in whom a satisfactory neuropathological
diagnosis cannot be established [60] and the large contri-
bution by vascular lesions to neurodegenerative disease
expression [61 – 63] argue for caution in the role accorded
post-mortem examination of the brain. On the other hand,
given the ambivalent status of some lesions as exposures
and outcomes and the relationship between an adverse
vascular profile and adverse outcomes in the absence of
neuroimaged lesions, it would seem wrong to toss out
neuropathology as a ‘‘gold standard’’ only to embrace
neuroimaging. The CIVIC experience suggests that neuro-
imaging lesions should be seen as supportive –even highly
supportive (for example, necessary for a ‘‘probable’’
diagnosis) – of VCI, but not essential.
Recently, a proposal has been made to, in effect, set aside
most of the evidence about VCI in favour of the newly
introduced concept of ‘‘vascular cognitive disorder’’ (VCD)
[2]. The essential difference between VCI and VCD is in the
approach to the diagnosis of dementia and in the rejection of
a gradient of impairment in favour of ‘‘bona fide irrefutable
cases of the disease.’’ How the VCI/VCD debate will evolve
remains unclear. For now, the existence of the idea that a
new approach might be preferable is not a persuasive
argument to ignore empirical studies. Nevertheless, VCI/
VCD/VaD is clearly an area in which additional debate (and
not just additional data) can help illuminate the tricky but
tractable question of how cerebrovascular disease affects
cognition.
If VCI is to be understood as a broadly defined construct,
sub-grouping is necessary. In this memory-clinic based
study, we found that both clinical and radiographic features
were important in defining VCI and in identifying subtypes.
Once clinical subtypes had been established, however,
 K. Rockwood et al. / Journal of the Neurological Sciences 240 (2006) 7 – 14
meaningful differences in death and institutionalization were
more strongly associated with clinical characteristics than
with neuroimaging features.
5. Competing interest statement
This is an original work that is not submitted elsewhere.
Each of the coauthors has made a substantial contribution to
the paper, as outlined. The study was sponsored by the
Canadian Institutes of Health Research and in part by its
predecessor, the Medical Research Council of Canada, then
through a partnership program with the company once
known as Hoechst Marion Roussel. None of the sponsors
has had any role in the initiation of the work, the data
collection, or the analysis of the data, which are located with
and analysed by my group, allowing me to take public
responsibility for the entire work.
Acknowledgements
The CIVIC study was funded by grants from the Medical
Research Council of Canada through the PMAC/MRC
program, with support from Hoechst Marion Roussel
Canada, and by the Alzheimer Society of Canada. Addi-
tional funding for these analyses came from the Canadian
Institutes of Health Research (CIHR) grant number MOP
62823.
Kenneth Rockwood and Chris MacKnight receive sup-
port from the CIHR through Investigator and New Inves-
tigator awards, respectively. Kenneth Rockwood is also
supported by the Dalhousie Medical Research Foundation
as Kathryn Allen Weldon Professor of Alzheimer Research.
David Hogan receives career support as the Brenda
Strafford Foundation Chair in Geriatric Medicine at the
University of Calgary.
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