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Archives of Clinical Neuropsychology

19 (2004) 745–757

The neuropsychological profile of vascular cognitive


impairment—no dementia: comparisons to patients at risk
for cerebrovascular disease and vascular dementia
Kelly Davis Garrett a,b,∗ , Jeffrey N. Browndyke a , William Whelihan a ,
Robert H. Paul a , Margaret DiCarlo a , David J. Moser c ,
Ronald A. Cohen a , Brian R. Ott d
a
Department of Psychiatry and Human Behavior, Brown Medical School, USA
b
Neuropsychology Program, Drexel University, USA
c
Department of Psychiatry, University of Iowa School of Medicine, USA
d
Department of Clinical Neuroscience, Brown Medical School, USA
Accepted 16 September 2003

Abstract

Hachinski and co-workers have used the term vascular cognitive impairment—no dementia (VaCIND)
to represent the earliest stages of cognitive decline associated with vascular changes [Neurology 57 (4)
(2001) 714]. However, the neuropsychological profile of vascular CIND remains unclear. Twenty-five
healthy elders, 29 individuals at risk for cerebrovascular disease (R-CVD), 18 individuals with VaCIND,
and 26 individuals with vascular dementia (VaD) were examined to determine whether patterns of neu-
ropsychological assessment performance can assist in the differentiation of patients at varying levels
of risk and severity for cerebrovascular disease and VaD. The R-CVD group performed within nor-
mal expectations on most cognitive measures as compared to the elderly control sample and published
clinical norms. Relative to elderly controls, the VaCIND group demonstrated significant difficulties on
measures of cognitive flexibility, verbal retrieval, and verbal recognition memory, but not on measures
of confrontational naming or verbal fluency. The VaD group was impaired on all cognitive measures
assessed. The current findings suggest that poor cognitive flexibility and verbal retrieval in the context
of preserved function in other domains may characterize the prodromal stage of VaD.
© 2003 Published by Elsevier Ltd on behalf of National Academy of Neuropsychology.

Keywords: Dementia; Vascular dementia; Cerebrovascular disease; Cardiovascular disease; Cognitive


impairment—no dementia (CIND); Neuropsychological assessment


Corresponding author. Present address: Cache County Study on Memory in Aging, Utah State University,
4440 Old Main Hill-UMC 4440, Logan, UT 84322-4440, USA.
E-mail address: kelly@drexel.edu (K.D. Garrett).

0887-6177/$ – see front matter © 2003 National Academy of Neuropsychology.


doi:10.1016/j.acn.2003.09.008
746 K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757

1. Introduction

Vascular dementia (VaD) has been the subject of increased clinical research, though far
less is known about the factors that contribute to the development of dementia among people
with chronic cerebrovascular disease (CVD) compared to Alzheimer’s disease (AD). A greater
understanding of the development of neurocognitive impairments during the early stages of
VaD may have significant clinical implications, as therapeutic interventions initiated early in
the disease course may prevent progression to dementia (Bowler, 2000; Devasenapathy &
Hachinski, 2000; Hachinski & Bowler, 1993).

1.1. The continuum of vascular cognitive impairment

A broad spectrum of cognitive and functional impairment may occur among patients with
CVD and VaD. Hachinski and co-workers (Bowler, 2000; Bowler, Steenhuis, & Hachin-
ski, 1999; Devasenapathy & Hachinski, 2000; Hachinski & Bowler, 1993) proposed that
vascular-related cognitive impairments exist on a continuum that is composed of three primary
stages; brain-at-risk (R-CVD), cognitive impairment—no dementia (CIND), and vascular de-
mentia (VaD). Collectively, the continuum is referred to as vascular cognitive impairment. Em-
pirical support for the concept of vascular cognitive impairment has begun to develop, including
a particular interest in the early phases of the process (Bowler, 2000; Bowler et al., 1999).
The first hypothesized stage in the development of VaD is the brain-at-risk stage. These
individuals suffer from cardiovascular or other system disease processes and are at risk for
developing cerebrovascular disease. However, they are not exhibiting clinically significant or
functional impairments.
The second stage is vascular cognitive impairment—no dementia (Hachinski, 1993, p. 26).
This term was introduced to identify the earliest clinical stage of on the continuum of vascular
cognitive impairment. VaCIND is analogous to mild cognitive impairment (MCI); a term
used to describe the prodromal stage of AD (Morris, 1993; Petersen et al., 1999). Like MCI,
individuals with VaCIND do not have significant impairment in their ability to complete basic
activities of daily living, and therefore the criteria for dementia are not satisfied (according
to the DSM). While the prognostic value of VaCIND as a diagnostic entity has not been
fully determined, preliminary data support the validity of the concept as the prodromal stage
of VaD. Wentzel et al. (2001) recently reported that half of individuals in their sample who
met criteria for VaCIND developed dementia over a five-year course. These findings suggest
that individuals with cognitive difficulties secondary to CVD are at increased risk for further
cognitive decline and conversion to dementia.
To our knowledge, the neuropsychological profile of vascular CIND has not received sig-
nificant study. The cognitive difficulties that are typically associated with cardiac disease and
mild CVD include reduced information processing speed, reduced cognitive flexibility, and
poor learning efficiency (Kilander et al., 1998; Rockwood, Dobbs, Rule, Howlett, & Black,
1992; Waldstein et al., 1996). Recent neuroimaging studies conclude that the magnitude of
cognitive impairment among patients with mild cardiovascular is significantly associated with
neuropathological changes secondary to vascular damage (Chui & Gonthier, 1999). Further
support for this position includes studies that demonstrate strong relationships between mid-life
K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757 747

blood pressure and the subsequent development of white mater pathology on neuroimaging and
associated cognitive decline (DeCarli et al., 2001; Swan et al., 1998). Collectively, these find-
ings suggest that cardiac risk factors can be associated with cognitive and neuropathological
changes in the absence of frank stroke or dementia (Skoog, 1994).

1.2. Purpose and predictions

The finding that cognitive functions mediated by frontostriatal circuits (e.g., select executive
and retrieval functions) are most disturbed in both the early and late phases of vascular-related
cognitive impairment raises the possibility that mild changes in these cognitive functions may
occur during the prodromal stage of VaD. However, it remains unclear whether clinically
meaningful changes are evident among patients at risk for CVD or patients with VaCIND.
Furthermore, it is of clinical interest to determine if the difficulties on measures of frontostriatal
function exist in the context of preserved function in other cognitive domains. A pattern of
strengths and weaknesses on cognitive measures may prove to be a critical determinant of
diagnostic differentiation between the various stages of vascular-related cognitive impairment,
as well as distinguishing vascular etiologies from other dementing conditions. To this end, the
identification of a pattern of neuropsychological changes associated with the early stage of
VaD (i.e., VaCIND) would greatly benefit diagnosis and facilitate intervention.
In the present study, we examined performances of three groups of patients at different stages
on the vascular cognitive impairment continuum using standard neuropsychological measures.
Normal elderly controls (EC), individuals at risk for CVD (R-CVD), individuals with VaCIND,
and individuals with VaD were compared on tests of cognitive flexibility, verbal fluency,
confrontation naming, verbal list-learning and verbal memory. We predicted that VaD patients
would exhibit the most profound deficits across the cognitive measures. Furthermore, we
predicted that individuals with VaCIND would exhibit deficits on measures sensitive to frontal
dysfunction, and similar, though less severe difficulties would be evident for the R-CVD group.
While a longitudinal study of individuals with R-CVD and subsequent VaD is desirable, we
address these predictions by employing a cross-sectional design in an attempt to elucidate hy-
potheses regarding the pattern of cognitive decline from R-CVD to VaCIND and subsequently
to VaD. We addressed these predictions using two types of analyses. First, a quasi-experimental
approach using between-group analyses of raw scores was employed to evaluate the relative
differences of individuals along the continuum of vascular cognitive impairment. Second, to
assess the clinical profile of these groups, scaled scores were derived from well-established
normative data for each of the measures, compared among the groups. The latter analyses
were conducted to assess the profile of VaCIND in a manner similar to the procedures clinical
neuropsychologists typically employ when examining individuals in clinical practice.

2. Methods

2.1. Participants

Data were obtained from archival records for the EC, VaCIND, and VaD groups, and from
an ongoing study for the R-CVD group. For all participants, individuals were excluded if
748 K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757

they had a major medical illness not directly related to group status, neurologic condition
(including traumatic brain injury, seizures), or history of chronic substance abuse or psychiatric
disturbance (including depression or significant depressive features).
The EC group consisted of 25 community-dwelling individuals, with no history of cardiac,
neurologic, or psychiatric conditions. The neuropsychological status of this sample has been
described previously (Cohen et al., 2002). The R-CVD group included 29 individuals enrolled
in a cardiac rehabilitation program and who volunteered to participate in a longitudinal study
of cardiac health and cognitive functioning in the elderly. All individuals in the R-CVD group
had documented evidence of cardiac disease including myocardial infarction (n = 18), hyper-
tension (n = 18), and/or had undergone coronary artery bypass graft surgery (n = 6) or valve
replacement surgery (n = 1). All participants received cognitive testing at least one month
post-surgery. Participants in the R-CVD group were not selected based on cognitive status.
The VaCIND group consisted of 18 individuals drawn from a study to examine the relation-
ship between mild cognitive impairment and driving skill. The VaCIND group was selected
from a larger group of patients that met research criteria for MCI. Specifically, all individuals
in the VaCIND group received a score of 0.5 on the Clinical Dementia Rating Scale, indicating
cognitive disturbance of mild severity that did not interfere with daily function (Morris, 1993).
All individuals in the VaCIND group exhibited evidence of CVD either on neuroimaging
(n = 13) or upon neurologic examination (n = 5), and reported significant risk factors for
CVD, including hypertension and diabetes (n = 4). A mild decline in cognitive functioning,
as assessed by the Clinical Dementia Rating Scale, neuroimaging, neurologic exam, were
used as the criterion for MCI. While mild functional memory decline can alone yield a CDR
score of 0.5, functional memory decline was not the exclusive factor in selecting the VaCIND
participants. In all cases, the cognitive symptoms reported on the CDR were determined to
be associated with a vascular etiology. This determination was made by consensus following
review of clinical history. Performances on neuropsychological measures were not used to
confirm the presence or the severity of CVD or MCI, nor were they used in determining the
CDR ratings. Rather, report of cognitive/functional decline by self- and/or informant-report
was reflected in the CDR scores.
The VaD group consisted of 26 individuals that participated in a drug trial for the treatment
of VaD (Paul et al., 2001). All data reported in the present investigation were collected prior
to the initiation of drug treatment. Diagnosis of VaD was conducted by a board-certified
neurologist using DSM-IV (Diagnostic and Statistical Manual for Mental Disorders, 1994)
and NINDS-AIREN (Roman et al., 1993) criteria. The VaD patients were 55 years or older
and scored between 18 and 24 on the Folstein Mini Mental Status Exam (Folstein, Folstein,
& McHugh, 1975).
Significant differences between the patient groups were noted for MMSE total score
[F(2, 70) = 92.84, P < .001]. Follow-up comparisons of MMSE performance revealed that
the R-CVD, VaCIND, and VaD groups were statistically different from each other (Ps <
.001). Additionally, significant differences between groups were noted for age [F(2, 70) =
22.22, P < .001], as the R-CVD group was younger than the other clinical groups (Ps < .001).
Marginal between-group differences were noted for years of education [F(2, 70) = 3.16, P <
.05], but this appeared to be driven by the R-CVD group reporting more education than the
VaD group (P = .04). Considering age is one of the most common risk factors associated with
K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757 749

Table 1
Clinical and demographic variables
ECa R-CVDb CINDc VaDd
Variables (n = 25) (n = 29) (n = 18) (n = 26) Significant contrasts
MMSE, M (S.D.) 28.2 (1.3) 28.9 (1.7) 26.3 (2.4) 22.2 (1.4) EC > CIND∗∗
EC > VaD∗∗∗
R-CVD > CIND∗∗∗
R-CVD > VaD∗∗∗
CIND > VaD∗∗∗
Age, M (S.D.) 76.5 (8.9) 67.4 (7.3) 78.4 (6.4) 77.1 (5.4) VaD > R-CVD∗∗∗
CIND > R-CVD∗∗∗
Gender (% male) 44 62 56 66 none
Education (years), 12.4 (3.6) 14.9 (3.3) 13.6 (2.5) 12.8 (3.1) R-CVD > EC∗∗
M (S.D.)
R-CVD > VaD∗
Note. Significant contrasts were based upon omnibus procedure significance and reflect follow-up t-tests for inde-
pendent samples.
a
Elderly control group.
b
Brain-at-risk group.
c
Vascular cognitive impairment, no dementia group.
d
Vascular dementia group.

P < .05.
∗∗
P < .01.
∗∗∗
P < .001.

dementia, this difference was not surprising. The potential for age differences to account for a
portion of the variance in the dependent variables was minimized by the use of age-corrected
(and some education-corrected) scaled scores for our clinically based group comparisons (as
described in subsequent sections). The ratio of males to females was comparable among the
patient groups. Demographic information for the groups is listed in Table 1.

2.2. Procedure

A comprehensive protocol of neuropsychological measures was administered to participants


by either a trained research assistant or a neuropsychologist. The specific neuropsychological
measures that were included for analyses are described in the following.
The Trail Making Test is a measure of combined visual search and cognitive flexibility (Trails
A and B (Partington & Leiter, 1949; Spreen, 1991, p. 59). Age- and education-corrected scales
scores for the time to complete parts A and B, as well as raw time to completion, were the
dependent variables for both measures (Heaton, Grant, & Matthews, 1991).
To assess lexical verbal fluency abilities, participants were presented with the Controlled
Oral Word Association Test (COWAT) according to standard procedures (Benton & Hamsher,
1989). This task requires participants to generate words beginning with a letter of the alphabet
(i.e., F, A, and S) for a period of 60s, excluding proper nouns and root words with different end-
ings (e.g., fish, fishing, fished). Category verbal fluency was measured by asking participants
to generate exemplars of animals for 60s. The age- and education-corrected scaled scores, as
well as raw score, for the number of correct responses generated across the three letters (F, A,
750 K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757

S) was the dependent variable for COWAT. Similarly, the dependent measure for the animal
fluency task was the age and education-corrected scaled scores and raw scores of the number
of correct animals named in 60s.
The Boston Naming Test was used to assess confrontation naming (BNT; Kaplan, 1983,
p. 9). Semantic and phonemic cues were provided if participants were unable to spontaneously
generate responses. The dependent variable was the age- and education-corrected scaled score
of the sum of the correct spontaneous responses and the number of correct responses when
participants required semantic cues due to stimulus misperception.
Verbal list-learning and memory abilities were assessed via the California Verbal Learning
Test, Research Edition (Delis, Kramer, Kaplan, & Ober, 1987). Dependent variables from the
CVLT-R included age- and sex-corrected scaled scores for total recall across the list-learning
trials, performance on the long-delay free recall trial, and the recognition discriminability
score for the long-delay recognition trial; a percentage that reflects the number of correct
endorsements corrected for false positive errors.

2.3. Statistical analyses

Two sets of analyses were conducted. First, between-group analyses (univariate ANOVAs)
were conducted among the clinical groups using raw scores from each neuropsychological
measure. These were conducted to assess whether the difference between clinical groups was
large enough to warrant experimental/statistical significance. To determine if significant cog-
nitive difficulties exist in VaCIND patients relative to normal elderly individuals, independent
sample t-tests with multiple-comparison correction (Bonferroni corrected P < .008) were con-
ducted between the EC and the VaCIND groups only for each neuropsychological measure.
An additional set of analyses was conducted to assess the clinical profile of these patient
groups using scaled scores derived from comparisons to well-established normative data. This
was conducted to assess the profile of VaCIND in a manner that replicated the procedures clin-
ical neuropsychologists typically employ when examining individuals in clinical practice. Ad-
ditionally, it provided a correction for contrasts in demographic variables among groups sam-
pled. Furthermore, our convenience sample of healthy elders used in the quasi-experimental
comparisons is limited by a modest sample size. Thus, comparisons between clinical groups
using published normative data may represent a more clinically meaningful benchmark with
greater external validity.
Demographic-corrected scaled scores (possible range = 0–20, mean = 10, S.D. = 3)
were used as the dependent variables in these statistical analyses. Performances on the Trail
Making Test and the BNT were compared to normative data reported by Ivnik, Malec, and
Petersen (1989). Performances on the COWAT and animal fluency measures were compared to
normative data reported by Tombaugh and co-workers (Tombaugh, 1999). Age and education
corrections were calculated for performances on the Trail Making Test, BNT, COWAT, and
animal fluency. Performances on the CVLT-R were compared to normative data reported by
Paolo, Troster, and Ryan (1997), which included age- and sex-corrected norms for individuals
between the ages of 53 and 86. Education is not significantly associated with performance on the
CVLT-R (Paolo et al., 1997), but age and sex are strongly related to performance on this test. As
such, age and sex were considered in the calculation of standard scores on the CVLT-R indices.
K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757 751

3. Results

3.1. EC, R-CVD, VaCIND, and VaD group comparisons

In general, the EC and R-CVD groups were comparable on neuropsychological measures.


Statistically different performance was found on the BNT and COWAT due to the R-CVD
group’s exceptionally good performance on these measures (Table 2).
Independent sample t-tests of the EC and VaCIND groups revealed significant differences
between groups on CVLT total learning [t(41) = 5.0, P < .0001], CVLT recognition dis-

Table 2
Neuropsychological performance comparisons of elderly controls, brain-at-risk, cognitive impairment—no demen-
tia, and vascular dementia groups
Neuropsychological measures ECa CINDb Significant contrasts
Trails B, M (S.D.) 90.8 (33.5) 190.5 (76.3) CIND > EC ∗∗∗∗
CVLT total learning, M (S.D.) 50.1 (9.6) 34.4 (11.1) EC > CIND ∗∗∗∗
CVLT recognition discriminability, 0.93 (.08) 0.83 (.11) EC > CIND ∗∗∗
M (S.D.)
Boston Naming Test, M (S.D.) 52.7 (4.5) 50.6 (7.1) None
COWAT, M (S.D.) 29.4 (8.4) 31.8 (9.6) None
Category fluency, M (S.D.) 17.8 (6.2) 14.3 (4.1) None
R-CVDc CINDb VaDd
Trials A, M (S.D.) 43.2 (15.6) 54.3 (17.7) 94.7 (60.7) R-CVD < CIND∗
R-CVD < VaD∗∗∗
CIND < VaD∗∗
Trails B, M (S.D.) 114.4 (67.8) 190.5 (76.3) 264.5 (63.4) R-CVD < CIND∗∗
R-CVD < VaD∗∗∗
CIND < VaD∗∗
CVLT total learning, M (S.D.) 41.4 (67.8) 34.4 (11.1) 17.7 (7.0) R-CVD > VaD∗∗
CVLT recognition discriminability, 0.93 (.06) 0.83 (.11) 0.69 (.15) R-CVD > CIND∗
M (S.D.)
R-CVD > VaD∗∗
CIND > VaD∗
Boston Naming Test, M (S.D.) 56.1 (3.4) 50.6 (7.1) 37.1 (10.1) R-CVD > VaD∗
COWAT, M (S.D.) 40.7 (15.2) 31.8 (9.6) 18.5 (11.2) R-CVD > VaD∗∗
Category fluency, M (S.D.) 20.0 (5.5) 14.3 (4.1) 8.2 (4.1) R-CVD > CIND∗∗
R-CVD > VaD∗∗∗
CIND > VaD∗∗
Note. Significant contrasts reflect planned or post hoc independent sample t-tests.
a
Elderly control group (n = 25).
b
Vascular cognitive impairment—no dementia group (n = 18).
c
Brain-at-risk group (n = 29).
d
Vascular dementia group (n = 26).

P < .05.
∗∗
P < .01.
∗∗∗
P < .001.
∗∗∗∗
P < .0001.
752 K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757

criminability [t(41) = 3.5, P < .001], and Trails B total time [t(21.7) = 5.2, P < .0001].
There were no significant differences between the EC and VaCIND groups for the BNT or
the categorical and letter verbal fluency measure performances (see Table 2). Between-group
univariate ANOVAs for the patient groups were statistically significant for each of the cog-
nitive measures. Performances differed significantly among groups on the Trail Making Test,
Part A [F(2, 67) = 5.93, P < .05], Trail Making Test, Part B [F(2, 68) = 25.2, P < .001],
semantic fluency [F(2, 69) = 35.4, P < .001], and CVLT-R recognition discriminability
[F(2, 68) = 47.2, P < .001]. Additionally, overall ANOVAs were significant for the COWAT
[F(2, 70) = 19.5, P < .001], the BNT [F(2, 66) = 36.9, P < .001], CVLT-R immediate
free recall [F(2, 68) = 38.3, P < .001] and delayed free recall [F(2, 67) = 34.3, P < .001].
Post hoc comparisons of these measures revealed significant differences between each of the
three groups on Trail Making Test, Part B (Ps < .002), semantic fluency (Ps < .01), CVLT-R
recognition discriminability (Ps < .04). By contrast, the R-CVD group and the VaCIND group
did not differ from one another on the COWAT (P = .08), BNT (P = .12), or CVLT-R imme-
diate free recall (P = .06). Statistically significant post hoc contrasts and their relationships
are noted in Table 2.

3.2. Clinical interpretations: comparison of R-CVD, VaCIND, and VaD groups to


published norms

Additional analyses were conducted using scaled scores based on published normative
data. This type of analysis was conducted to assess the profile of VaCIND in a manner similar
to standard clinical practice. The R-CVD group performed similarly to normative samples
on most of the cognitive measures. Mean scaled scores (SS) for the R-CVD group did not

Fig. 1. Mean scaled score comparisons of brain-at-risk (R-CVD), vascular cognitive impairment—no dementia
(VaCIND), and vascular dementia (VaD) groups on neuropsychological measures.
K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757 753

into the impaired range (defined as a standard score ≤7). VaCIND group performance was
more variable among the cognitive measures. On measures of cognitive flexibility, this group
performed in the mild impairment range (Trails B; mean SS = 6.8). Subtle difficulties were
also evident on the CVLT-R total learning (mean SS = 7.1) and long-delay free recall (mean
SS = 7.3). By contrast, the VaCIND group performed within normative expectations on the
BNT, COWAT and category fluency, and CVLT-R recognition discriminability. As reported
in an earlier study (Cohen et al., 1999) the VaD group included in the current investigation
performed uniformly well-below normative expectations and were considered to be in the
moderate to severe impairment range on virtually all of the cognitive measures. Mean scaled
scores for these measures are represented in Figure 1.

4. Discussion

In the present study, we examined the neuropsychological status of individuals with CVD,
mild cognitive impairment with cerebrovascular risk (VaCIND), and VaD. Two approaches
were taken to examine VaCIND: a quasi-experimental approach and a clinical comparison. The
clinical approach was undertaken in an attempt to comment on the profile of VaCIND using
tools for standard clinical assessment (i.e., well-known normative data). Our results suggest
that patients with vascular VaCIND are characterized by a neuropsychological performance
pattern involving subtle difficulty with cognitive flexibility and additional difficulty, though
less significant, on immediate verbal retrieval. In comparison, verbal fluency, confrontation
naming, and long-term verbal recognition memory were within the normal ranges for this
group.
The discrepancies between the clinical and quasi-experimental approaches underscore the
importance of selecting appropriate norms and healthy elderly referents. Unfortunately, our EC
group was a post hoc referent group of convenience and was younger than clinical groups. To
address these issues, future studies should consider employing a within-subjects longitudinal
study of healthy elders and R-CVD individuals to study their natural course.
Based on these results, a hypothetical timeline can be formulated that tracks the progres-
sion of cardiac risk and the neurocognitive skills impacted at the earliest stages to VaD (see
Fig. 2). The R-CVD group exhibited intact cognitive performances compared to normative
data, whereas individuals with VaD were impaired on all of the cognitive tests administered.
It was not surprising to find that the R-CVD group performed within the average range, as
these participants were not recruited on the basis of existing cognitive difficulties or subjective
complaints of cognitive disturbance. Nevertheless, previous studies have demonstrated that
cardiac disease, especially left ejection fraction and hypertension, is significantly associated
with poorer performance on tests of psychomotor speed and verbal memory (Leys et al., 1999).
As such, it is possible that a subset of individuals in the R-CVD group would eventually exhibit
cognitive difficulties associated with increased cardiovascular and subsequent cerebrovascular
disease. Further, it is possible that our failure to find cognitive impairments in this group is
based, in part, upon the heterogeneity of cardiac difficulties in our R-CVD sample. However,
clinical generalizability may be improved with a subject pool with heterogeneous cardiac
profiles as this may be more representative of a clinical population with CVD risks.
754 K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757

Fig. 2. Hypothesized progression of cardiac risk factors to cognitive impairment—no dementia to vascular dementia.

Our findings for the VaCIND group have been incorporated into this proposed timeline,
but our results are certainly preliminary, and validation of this timeline requires replication
of these findings. The VaD group (progressive type) has been described in the literature, with
early executive impairment, slowed psychomotor functioning, retrieval-based memory deficits,
decline in ADLs, and frequent depressive features (Bartres-Faz, Clemente, & Junque, 2001;
Cohen & Kaplan, 1998; Corbett, Bennett, & Kos, 1994; Kramer-Ginsberg et al., 1999; Libon
et al., 2001; Naarding et al., 2003; O’Sullivan et al., 2001).

4.1. Implications for differentiation between vascular CIND and Alzheimer’s-related mild
cognitive impairment

Interestingly, the pattern of cognitive performances observed for the VaCIND group may
be different than that of individuals with mild cognitive impairment associated with prominent
memory impairment (Petersen et al., 1999). Our work would suggest that individuals with
VaCIND present with problems in cognitive flexibility in addition to memory (retrieval) diffi-
culties and a history of cardio- and cerebrovascular risk factors. While some researchers have
reported executive disturbances in prodromal AD (e.g., Nagahama, 2003, p. 75), the cardio-
and cerebrovascular risk factors are often not well characterized among AD patients in these
reports. Thus, these findings of subtle executive and amnestic deficits in AD may represent
Alzheimer’s pathology combined microvascular inefficiency (without frank infarct).
To that end, the use of specific monikers to describe “mild cognitive impairment” or the
continuum of “early vascular impairment/VaCIND” may be a subtle, yet important distinction
as the criterion of mild memory impairment with intact cognitive functioning in other domains
(e.g., Petersen, 1999, p. 34) may not be appropriate in describing VaCIND (Bowler et al., 1999;
K.D. Garrett et al. / Archives of Clinical Neuropsychology 19 (2004) 745–757 755

Rockwood et al., 1992). Furthermore, these syndromes may indeed represent prodromes to
distinct etiologies (e.g., vascular, probable Alzheimer’s, mixed). Nonetheless, the longitudinal
outcome of VaCIND and MCI (Petersen et al., 1999) may not predict future VaD and AD
diagnoses, respectively, (e.g., Ingles et al., 2002, p. 76).

4.2. Considerations for future research

Criteria for VaCIND have been introduced by Bowler and Hachinski, but are certainly
preliminary, as they do not suggest a particular neuropsychological profile to support the
diagnosis (Bowler et al., 1999). Our data suggest that such criteria may include a neurocognitive
profile of poor cognitive flexibility and impaired verbal retrieval in the presence of intact
recognition memory. Our data are admittedly preliminary, though support for impaired verbal
retrieval (as evidenced by relatively preserved recognition memory) has been demonstrated
among patients with subcortical ischemic vascular dementia without cortical strokes (Davis,
2002). Identifying neurocognitive criteria for VaCIND would be best achieved in a longitudinal
study examining several domains of cognitive function among individuals with R-CVD (i.e.,
not using the mild memory criterion for MCI). To address this need, a five-year investigation of
individuals at risk for cerebrovascular disease is currently underway in our laboratory, which
includes direct measures of cardiac function and serial structural MRI studies.

Acknowledgments

Portions of this work were supported by a grant from Indevus Pharmaceutical Corporation
to Dr. Cohen.

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