BRAIN AND COGNITION 31, 269–282 (1996)

ARTICLE NO. 0045

Neuropsychological Aspects of Vascular Dementia

SUSAN E. MCPHERSON
Neuroscience Associates, Inc., and Department of Psychiatry and Biobehavioral Sciences,
UCLA School of Medicine

AND

JEFFERY L. CUMMINGS
UCLA Alzheimer’s Disease Center and Departments of Neurology and Psychiatry and
Biobehavioral Science, UCLA School of Medicine, and Behavioral Neuroscience Section,
Psychiatry Service, West Los Angeles Veteran Affairs Medical Center

Vascular dementia (VaD) is the second most common cause of dementia in the
elderly. Neuropsychologically, VaD has been characterized traditionally as having
a ‘‘patchy’’ pattern of cognitive deficits. Newly developed diagnostic criteria for
VaD suggest that this ‘‘patchy’’ pattern is associated with one type of VaD—multi-
ple cortical infarctions, and that several additional subtypes of VaD exist, each fea-
turing a characteristic pattern of neuropsychological deficits. Strategic infarct de-
mentias have unique features that reflect the specific brain region affected. Lacunar
state and Binswanger’s disease produce subcortical dementia with disproportionate
executive dysfunction. The profile of neuropsychological disturbances observed in
VaD patients provides important insight into the localization and pathophysiology
of the underlying cerebrovascular disease.  1996 Academic Press, Inc.

Vascular dementia (VaD) and Alzheimer’s Disease (AD) are the two most
common causes of dementia in the elderly (Roman, 1991). Although AD
accounts for approximately 50% of all cases of dementia, VaD has been
estimated to account for approximately 15–20% of cases of dementia
(Mirsen & Hachinski, 1988). Relative to vascular dementia, the cognitive
changes associated with Alzheimer’s disease have been studied extensively,
and are better defined, and uniform diagnostic criteria exist. Despite rela-
tively high prevalence, VaD has not been studied as extensively. Epidemio-

This project was supported by the Department of Veteran Affairs and a National Institute
on Aging Alzheimer’s Disease Core Center grant (AG10123). Address correspondence and
reprint requests to Jeffrey L. Cummings, UCLA Alzheimer’s Disease Center, 760 Westwood
Plaza, Los Angeles, CA 90024-1759.
269
0278-7626/96 $18.00
Copyright  1996 by Academic Press, Inc.
All rights of reproduction in any form reserved.
270 MCPHERSON AND CUMMINGS

logic studies reveal that the prevalence of stroke rises exponentially with
age, doubling each decade (Kurtzke, 1985). There may be as many as
430,000 elderly persons in the United States with stroke and dementia and,
in at least 62% of these patients, dementia may be the direct result of cerebro-
vascular disease (Tatemichi, Desmond, & Mayeux, 1992). Studies world-
wide have found consistent increases in the prevalence of VaD with advanc-
ing age (Rocca et al., 1991; Suzuki, Katsuzawa, Nakajinia, & Hatano, 1991;
Yamaguchi, Ogata, & Yoshida, 1992).
Research on VaD has been limited by the heterogeneity of the disease
and by grouping together patients with a variety of types of neuropathologic
changes. For example, lesions may appear in a combination of brain regions
(e.g., cortical and subcortical), can be strategic (small localized ischemic
damage) in location (e.g., thalamus), or may appear solely in cortical or sub-
cortical regions. Recent research definitions developed by an international
committee of experts from the National Institute of Neurological Diseases
and Stroke (NINDS) and the Association Internationale pour la Recherche
et l’Enseignement en Neurosciences (AIREN) resolve this heterogeneity by
classifying the disease into distinct subgroups of cerebrovascular lesions
(Roman et al., 1993). With these criteria, it is feasible to identify distinct
patterns of neuropsychological test performance in each of the subtypes of
VaD.
The literature on VaD is limited and has been inconsistent in describing
a characteristic pattern of neuropsychologic test outcomes. Many studies
which focused on cognitive deficits associated with VaD have combined all
patients with cerebrovascular pathology into a single group, regardless of
the location or severity of lesions. The ‘‘patchy’’ deficits often thought to
be characteristic of multi-infarct dementia may be an artifact of studying
patients with a variety of neuropathologic changes (Perez et al., 1975). This
review: (1) presents the new diagnostic criteria for VaD, (2) reviews avail-
able studies that characterize the new subtypes, and (3) provides suggestions
for future directions in research.

DIAGNOSTIC CRITERIA
The most recent edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV; American Psychiatric Association, 1994) has aban-
doned the term ‘‘multi-infarct dementia’’ and has adopted the terminology
‘‘vascular dementia.’’ The DSM-IV definition of VaD is as follows: (1) evi-
dence of memory impairment, marked by an inability to learn new informa-
tion or recall previously learned information and one or more of the follow-
ing cognitive disturbances: aphasia, apraxia, agnosia, or disturbances of
executive function; (2) the cognitive deficits cause significant impairment in
social or occupational functioning and represent decline from a previous
level of functioning; (3) focal neurological signs and symptoms are present
 VASCULAR DEMENTIA 271

or there is laboratory evidence of cerebrovascular disease that are judged to

be etiologically related to the disturbance; and (4) the deficits do not occur
exclusively in the course of the delirium. The course of the disease is de-
scribed as abrupt followed by a stepwise and fluctuating course, with a
‘‘patchy’’ pattern of deficits depending upon which regions of the brain have
been damaged. These diagnostic criteria do not specify subtypes of VaD.
Recently, new diagnostic criteria for VaD, which recognize six distinct
subtypes, has been developed. The NINDS-AIREN International workgroup
criteria for diagnosis of probable VaD include: (1) a diagnosis of dementia,
(2) evidence of cerebrovascular disease defined by the presence of focal signs
on neurologic examination and evidence of relevant cerebrovascular disease
by brain imaging, and (3) a relationship of the above two disorders mani-
fested or by the presence of one of the following: (a) onset of dementia
within 3 months of a recognized stroke, (b) abrupt deterioration in cognitive
functions, or fluctuating, stepwise progression of cognitive deficits (Roman
et al., 1993). According to these criteria, dementia is defined as a decline in
memory and intellectual abilities that causes impairment in ability to function
in daily living. Impaired functioning in daily living must be due to cognitive
impairment and not secondary to physical handicaps produced by stroke.
Cognitive decline is manifested by impairment of memory and deficits in at
least two additional domains, including orientation, attention, language-ver-
bal skills, visuospatial abilities, calculations, executive functions, motor con-
trol, praxis, abstraction, and judgment.
The neuropathological definition of VaD includes dementia resulting from
ischemic and hemorrhagic brain lesions and from cerebral ischemic-hypoxic
injuries such as those caused by cardiac arrest. Cases due to pure asphyxia,
respiratory failure, carbon monoxide poisoning, or cyanide poisoning are
excluded (Roman et al., 1993). The following VaD syndromes are recog-
nized (Table 1): (1) multi-infarct dementia (involving both cortical and sub-
cortical regions), (2) strategic single-infarct dementia, (3) small-vessel dis-
ease with dementia, (4) hypoperfusion, (5) hemorrhagic dementia, and
(6) combinations of the above lesions and other yet-unknown factors (Roman
et al., 1993). The first three conditions have received modest attention in the
neuropsychology literature and will be discussed in detail.

NEUROPSYCHOLOGICAL ASPECTS OF MULTIPLE INFARCTS

Relatively few studies of the neuropsychological aspects of MID exist.
Furthermore, the majority of studies have relied on relatively small sample
sizes and have combined all patients with cerebrovascular pathology into a
single group, resulting in a heterogeneous or ‘‘patchy’’ pattern of deficits.
For example, Perez and colleagues (1975) found that patients with MID ex-
hibited more subtest scatter on the Wechsler Adult Intelligence Scale
(WAIS) compared with patients with AD or vertebrobasilar insufficiency
272 MCPHERSON AND CUMMINGS

TABLE 1
Classification and Neuropsychological Features of VaD Syndromes
VaD Type Neuropsychological Deficits

MID
Cortical
Mixed (cortical and subcortical)
Strategic Infarct Dementia
Angular Gyrus Syndrome
Caudate Infarction
Globus Pallidus Infarction
Thalamic Infarction
Small Vessel Disorders
Lacunar State
Binswanger’s Disease
Aphasia, agnosia, amnesia, apraxia
Variable pattern of deficits including language and
memory
Anomia, alexia with agraphia, Gerstmann syndrome,
constructional disturbance
Deficits of memory, attention, set shifting, verbal flu-
ency; planning, organizing and sequencing
Disorders of memory and set shifting
Abnormalities of memory, verbal fluency, mental con-
trol, set shifting, sequential reasoning, motor pro-
gramming
Deficits of set shifting, verbal fluency, attention ab-
straction
Impairment of memory, attention, gait disturbance,
motor performance, set shifting.

(VBI). These investigators concluded that the lack of homogeneity in test

scores reflected the patchy nature of the disease process as well as variation
in the ‘‘site, location, extent and number of cerebral infarctions.’’ Approxi-
mately 50% of normal adults exhibit differences of seven or more points
between scaled scores on WAIS-R subtests (LaRue, 1992), however, and
‘‘patchy’’ deficits alone are not diagnostic of MID.
Until recently, no uniform diagnostic criteria existed to define MID. The
studies listed below used varied criteria for identifying patients with MID,
usually based on the presence of infarct on computed tomography (CT), and
varied criteria for assigning level of severity.
Investigations of language have suggested that compared to patients with
AD, MID patients utter fewer words and exhibit shorter phrase length, re-
stricted lexical variability, and simplified syntax (Hier, Hagenlocker, & Shin-
dler, 1985). Patients with MID have speech regulation disorders such as per-
severation and intrusions (Shindler, Caplan, & Hier, 1984) and impairment of
mechanical aspects of speech (e.g., pitch, melody, articulation, rate) (Powell,
Cummings, Hill, & Benson, 1988). They have deficits on tasks of confronta-
tion naming, although less severe than those of comparably demented AD
patients (Powell et al., 1988). Verbal fluency has been found to be impaired
in MID (Gainotti, Galtagirone, Masullo, & Miceli, 1980). Kontiola and col-
leagues (1990) reported disorders of word recognition, naming, and repeti-
tion in patients with MID, compared to patients with AD.
Not all studies, however, have shown language differences to be helpful
 VASCULAR DEMENTIA 273

in distinguishing MID from AD. At least two studies have found no differ-
ences on tests of confrontation naming and verbal fluency (Fischer, Gatterer,
Marterer, & Danielczyk, 1988; Loewenstein et al., 1991).
Studies of memory functions in MID have failed to show differences be-
tween patients with AD and MID when level of severity of dementia was
controlled. LaRue (1989) administered the Object Memory Evaluation (Fuld,
1981) to nine inpatients with MID. Three of the patients performed within
normal limits, one patient had marked retrieval deficits, one patient had an
amnestic-type memory deficit, and four were impaired in storage. Variability
in performance was related to the overall severity of dementia and to the
presence or absence of depression. Loewenstein and colleagues (1991) re-
ported that patients with AD made more intrusion errors on the Object Mem-
ory Evaluation as compared with patients with MID.
The studies cited above did not use uniform criteria in defining MID. As
a result, a patient with any lesion was admitted to the MID group. As will
be stated below, patients with only subcortical infarcts present with a differ-
ent pattern of cognitive deficits compared to patients who meet the NINDS-
AIREN criteria for MID. These criteria define the cerebrovascular lesions
associated with the multiple infarction syndrome as multiple large complete
infarcts usually involving cortical and subcortical areas. These criteria allow
for the possibility that multiple infarcts limited to the cortex may cause MID.
Cortical infarction most often results from embolic or thrombotic occlusion
of large and/or medium sized vessels. When multiple, bilateral cortical in-
farcts are present, the clinical picture can meet diagnostic criteria for demen-
tia (Cummings & Benson, 1992). The cognitive deficits associated with corti-
cal MID depends on the cortical territory irrigated by the involved vessel.
Occlusions to the middle cerebral artery affecting the left hemisphere typi-
cally result in aphasia and apraxia (Benson, 1979; Benson & Geschwind,
1975; Geschwind, 1975). Nonfluent aphasias result from infarctions anterior
to the Rolandic fissure and fluent aphasic output is associated with lesions
posterior to the central fissure (Cummings & Benson, 1992). Repetition is
disrupted following infarction immediately adjacent to the sylvian fissure.
However, when the perisylvian area is spared, the ability to repeat is pre-
served. Global aphasia is the result of infarction of the entire dominant mid-
dle cerebral artery territory. Abnormalities in language melody, dressing,
and problems with visuospatial orientation and visuomotor performance may
occur following right middle cerebral artery infarction (Hemphill & Klein,
1948; Ross, 1981).

NEUROPSYCHOLOGICAL ASPECTS OF STRATEGIC

SINGLE-INFARCTS
Advances in diagnostic imaging have now made it possible to recognize
small infarctions strategically located to disrupt multiple cognitive domains.
274 MCPHERSON AND CUMMINGS

These lesions may be located cortically or subcortically. Four anatomical

areas have been identified as producing a multifaceted dementia syndrome.
These areas are the: angular gyrus, caudate nucleus, globus pallidus, and
thalamus.

Angular Gyrus Syndrome

Angular gyrus syndrome, resulting from lesions in the inferior lobule,
shares several clinical features with AD (Cummings & Benson, 1992). The
complete syndrome includes fluent aphasia, alexia with agraphia, Gerstmann
syndrome (acalculia, right–left disorientation, dysgraphia, and finger agno-
sia), and constructional disturbance. Focal motor and/or sensory signs may
be absent and the lesions are not always detected by CT, making the syn-
drome difficult to distinguish from AD. However, while AD patients are
often unaware of language and memory problems, patients with angular gy-
rus syndrome frequently complain of their language disturbance (e.g., inabil-
ity to remember names) and tend to be frustrated and apologetic about their
inability to communicate. Patients with AD and those with angular gyrus
syndrome both make verbal paraphasias. However, the paraphasias made by
patients with angular gyrus syndrome are closer to the target word. Reading
comprehension is impaired in both conditions.

Caudate Infarcts
The caudate nucleus, globus pallidus, and thalamus connect neuroanatomi-
cally with the dorsolateral prefrontal cortex to form the dorsolateral prefron-
tal-subcortical circuit (Cummings, 1993). Damage to this circuit results pri-
marily in deficits in executive functions and motor programming and patients
with such deficits often meet criteria for dementia. The profile of neuropsy-
chological deficits and behavior changes varies depending upon which struc-
ture in the circuit has been damaged.
Few reports of focal caudate lesions exist. One study found that patients
with dorsal or ventral caudate lesions exhibited deficits in memory, attention,
and set shifting (Mendez, Adams, & Lewandowski, 1989). Behaviorally, the
patients with dorsal caudate lesions were confused and disinterested, while
patients with ventral caudate lesions were more disinhibited, euphoric, and
inappropriate (Mendez et al., 1989). Studies of animals with caudate lesions
have demonstrated impaired performance on tasks involving spatial choice
and memory and disruption of responses to reinforcement and conditioning
(Oberg & Divac, 1979).

Pallidal Infarcts
Reports of focal damage to the globus pallidus are also rare and are limited
to case studies of multi-case reports, many of which involved cases of dam-
 VASCULAR DEMENTIA 275

age secondary to carbon-monoxide poisoning. Deficits on tests of memory

and set shifting have been reported in one case study of bilateral globus
pallidus hemorrhages (Strub, 1989).

Thalamic Infarcts
An extensive body of literature exists on the neuropsychological sequelae
of strategic thalamic infarcts. Patients with bilateral paramedian thalamic
infarction present with cognitive deficits including poor memory (Eslinger,
Warner, Gratton, & Easton, 1991; Gentilini, De Renzi, & Crisi, 1987; Stuss,
Guberman, Nelson, & Larochelle, 1988), reduced verbal fluency, decreased
mental control, and intact language (Eslinger, Warner, Gratton, & Easton,
1991). Behavioral changes observed have included dysphoria, irritability and
disinhibition, apathy, utilization behavior, and distractibility (Bogousslavsky
et al., 1988; Eslinger et al., 1991; Gentilini et al., 1987).
Patients with thalamic infarction often manifest deficits on tests of ‘‘fron-
tal lobe’’ function. Case studies have revealed apathy, memory impairment,
poor word list generation, and poor executive functions in patients with left
medial dorsal thalamic infarction (Sandson, Daffner, Carvalho, & Mesulam,
1991). Other executive deficits include perseveration, inability to shift cogni-
tive set, decreased verbal fluency, and poor susceptibility to interference (Es-
linger et al., 1991; Mennemeier, Fennell, Valenstein, & Heilman, 1992;
Pepin & Pepin, 1993), poor sequential reasoning, and poor motor program-
ming (Eslinger et al., 1991; Mennemeier et al., 1992).
Damage to each of the structures described above disrupts the dorsolateral
prefrontal-subcortical circuit, resulting in a pattern of memory disturbance
and deficits of executive functions, meeting criteria for a diagnosis of de-
mentia.

NEUROPSYCHOLOGICAL ASPECTS OF SMALL VESSEL DISEASE

The deep gray matter nuclei (basal ganglia, thalamus) and deep white mat-
ter are irrigated by small vessels that penetrate from larger arteries. The small
vessels are subject to arteriosclerotic injuries and multiple occlusions can
produce a dementia syndrome. Small vessel disease can be broken down into
two categories: (1) lacunar state and (2) Binswanger’s disease.

Lacunar State
Lacunar state has been defined as the presence of numerous lacunes in
the basal ganglia, pons, and white matter of the centrum ovale (Roman,
1985). Lacunar state has been extensively studied, but very few studies have
included neuropsychological evaluations. Wolfe, Linn, Babikian, and Albert
(1990), using a test battery sensitive to deficits in executive functions, found
a pattern of frontal-lobe type deficits including difficulties in set shifting
276 MCPHERSON AND CUMMINGS

ability, decreased word list generation, and apathy in 11 patients with multi-
ple subcortical lacunes, 7 of whom had lacunes in both the basal ganglia
and periventricular white matter (PVWM).
Corbett, Bennett, and Kos (1994) reported that number of lacunes, extent
of periventricular lucency, and severity of ventricular enlargement but not
volume of infarction were associated with impaired performance on neuro-
psychological tests, specifically those thought to be dependent on frontal-
executive function such as phonemic and semantic fluency, simple attention,
and abstraction.
Recent progress in understanding frontal-subcortical circuits, particularly
the mediation of executive functions by the dorsolateral prefrontal circuit
(Cummings, 1993) facilities characterization of the types of deficits associ-
ated with small-vessel disease. The dorsolateral prefrontal circuit mediates
executive function and motor programming, and infarcts in subcortical re-
gions such as the basal ganglia and deep white matter disrupt the circuit,
resulting in deficits in these functions. The same subcortical structures that,
when infarcted, produce a syndrome of strategic infarct dementia, are also
affected in lacunar state.

Binswanger’s Disease
Binswanger’s disease (BD) is a gradually progressive syndrome caused
by ischemic injury to the deep white matter of the cerebral hemispheres.
Clinical risk factors for BD include hypertension, diabetes, cardiovascular
disease, and recurrent hypotension. Patients often have a history of repeated
small strokes, usually lacunae, and evidence of discrete neurologic deficits
(Babikian & Ropper, 1987; Caplan & Schoene, 1978; Goto, Ishii, & Fuka-
sawa, 1981; Loizou, Kendall, & Marshall, 1981; Nichols & Mohr, 1986;
Tomonaga, Yamanouchi, Tohgi, & Kemeyama, 1982). In a review of the
literature and position paper, Roman (1987) proposed that the white matter
disease consistent with BD may cause disconnection of subcortical structures
from an intact cerebral cortex and proposed the term senile dementia of the
Binswanger type (SDBT) to describe the associated form of VaD. Patients
with BD present with a slowly progressive dementia marked by pseudobul-
bar palsy, emotional incontinence, lateralized motor signs, corticospinal or
corticobulbar tract dysfunction, and gait disturbance (Aronson & Perl, 1974;
Babikian & Ropper, 1987; Biemond, 1970; Burger, Burch, & Kunze, 1976;
Caplan & Schoene, 1978; Garcin, Lapresle, & Leon, 1960; Goto et al., 1981;
Loizou et al., 1981; Nichols & Mohr, 1986; Tomonaga et al., 1982). Small-
stepped gait (marche à petits pas), frequent falls, and urinary urgency or
incontinence are typical early in the course of the disease (Roman, 1987).
Changes in mood and behavior (Babikian & Ropper, 1987), frontal lobe signs
(Lotz, Ballinger, & Quisling, 1986; Ishii, Nishihara, & Imamura, 1986) in-
cluding personality change, loss of incentive, reduced drive, and impaired
 VASCULAR DEMENTIA 277

insight, apathy, and abulia commonly occur. Patients with BD manifest mut-
ism, bradykinesia, rigidity, and dysarthria and may be confused diagnosti-
cally with patients with Parkinson’s disease with dementia or progressive
supranuclear palsy (Roman, 1987). Glabellar, snout, rooting and grasp re-
flexes, and bilateral or unilateral tract signs are usually present.
Neuropsychological investigations of BD are few. Studies to date have
focused on the relationship between neuropsychological test performance
and evidence of periventricular white matter changes. Rao and colleagues
(1989) administered an extensive neuropsychological battery to 50 normo-
tensive, middle-aged, healthy volunteers. Ten of the subjects showed deep
white-matter changes (leukoaraiosis) on magnetic resonance scans. No sig-
nificant neuropsychological differences were found between subjects with
and without white matter changes, and there was no relationship between
severity of leukoaraiosis and neuropsychological test performance. However,
the sample size was small and only 2 of the 10 subjects with white matter
changes had moderately severe white matter alteration. Steingart and col-
leagues (1987a) compared nondemented subjects with and without evidence
of leukoaraiosis on CT. The group with leukoaraiosis exhibited a higher fre-
quency of abnormal gait and focal neurologic signs, and performed worse
on tests of memory and language on a brief neuropsychological screening.
In a companion paper by the same authors (Steingart et al., 1987b), patients
with AD and evidence of leukoaraiosis performed more poorly cognitively
than AD patients without leukoaraiosis.
Libon and colleagues (1990) administered a battery of neuropsychologi-
cal tests to four groups of patients. All patients presented for diagnostic eval-
uation of memory or psychiatric problems. Group 1 had no evidence of deep
white matter disease or dementia; Group 2 had no diagnosis of dementia but
showed evidence of white matter changes on imaging, and Groups 3 and 4
showed evidence of dementia, without and with deep white matter changes,
respectively. As might be expected, patients with dementia (Groups 3 and
4) performed more poorly on memory tests of immediate and delayed recall
compared with the nondemented group of patients. Significant differences
were found between the two nondemented groups of patients (Group 1 and
2) on tests of memory, for both immediate and delayed recall. There was
no difference in the frequency of stroke and neurologic signs between Groups
1 and 2. The group of demented patients with white matter disease (Group
4) had more infarcts and focal neurologic signs than demented subjects with-
out white matter infarcts (Group 3). Although this study leaves many ques-
tions unanswered in terms of a pattern of neuropsychological deficits associ-
ated with BD, it provides evidence for BD, and suggests that patients who
show periventricular hyperintensities on magnetic resonance imaging (MRI)
may be at risk for developing a dementing illness.
A study by Boone and co-workers (1992) found executive deficits in pa-
tients with white matter lesion areas of greater than 10 cm2 compared with
278 MCPHERSON AND CUMMINGS

patients with smaller total area of infarction. These patients performed sig-
nificantly more poorly on tasks of simple and divided attention and made
more perseverative responses and achieved fewer categories on a card sorting
task. In contrast to the findings of Wolfe and co-workers, Boone and col-
leagues found no deficits on tests of word list generation. Neither study found
deficits on tests of memory.
Kertesz and Clydesdale (1994) compared patients with AD to those with
VaD (small-vessel disease) as defined by evidence of significant white matter
hyperintensities on MRI or leukoaraiosis on CT. Patients with AD performed
more poorly on tasks of memory and some language subtests. In comparison,
patients with VaD exhibited greater difficulty on tasks related to frontal lobe
functions including dysgraphia, motor performance, and sequential reason-
ing and analysis.
Recent neuropsychological investigations (Boone et al., 1992; Wolfe et
al., 1990) suggest that deficits of frontal functions in patients can be identified
before the onset of memory or other cognitive disturbances in patients with
small-vessel disease, and ischemic injury to deep hemispheric gray and white
matter structures. These findings suggest that changes in frontal functions
occur well before the onset of memory problems in subcortical VaD, are a
potential key to identifying patients at risk for developing VaD and may
differentiate patients with early VaD from those with AD.

Treatment of VaD
Treatment of stroke is pharmacologic and supportive. Antiplatelet agents
such as aspirin are prescribed for most patients with VaD. Ticlopidine, a
powerful new platelet antiaggregant, can help prevent stroke and worsening
of dementia in patients who do not respond to or cannot tolerate aspirin.
Leukopenia occurs in 2% of patients treated with ticlopidine and patients
are required to have a complete blood count (CBC) every other week for the
first 3 months of treatment. Embolic strokes are treated with anticoagulant
medications such as heparin, but this treatment is warranted only in relatively
high functioning patients without a gait disturbance and fall risk, who have
an identified source of cerebral emboli. In addition to pharmacologic treat-
ment to reduce the risk of stroke, patients may be treated with psychotropic
agents for depression, psychosis, or anxiety (Cummings & Benson, 1992).
Families of VaD patients should be referred for psychological counseling,
support group participation, community resources, and legal guidance.

Conclusion
NINDS-AIREN criteria provide for better definition of the VaD subtypes.
Future research should focus on the pattern of neuropsychological deficits
associated with each of the subtypes of VaD, including tests of frontal lobe
function. In addition, studies of patients at risk for developing VaD would
 VASCULAR DEMENTIA 279

be helpful in determining factors which might lead to or protect patients at

risk from developing a dementia syndrome.

SUMMARY
As new pharmacologic agents are made available for the treatment of
VaD, the accurate classification and neuropsychological characterization of
patients at risk will be a critical step in identifying persons who may benefit
from new, innovative drug therapies. The increased size of the elderly popu-
lation has made further study of small-vessel disease imperative and ad-
vances in medical technology, pharmacology, and neurophysiology make
improved understanding feasible. The sensitivity of MRI has made possible
the early detection of subcortical white matter lesions, heretofore invisible
on computed tomography (CT). Recent hypotheses regarding the frontal-
subcortical circuit anatomic linkages allow for hypothesis-driven research
regarding the phenomenology of VaD.

REFERENCES
American Psychiatric Association. 1994. Diagnostic and Statistical Manual of Mental Disor-
ders, 4th Ed. Washington, DC: American Psychiatric Association.
Aronson, S. M., & Perl, D. P. 1974. Clinical neuropathological conference. Diseases of the
Nervous System, 35, 286–291.
Babikian, V., & Ropper, A. H. 1987. Binswanger’s disease: A review. Stroke, 18, 2–12.
Benson, D. F. 1979. Aphasia, alexia, and agraphia. New York: Churchill Livingstone.
Benson, D. F., & Geschwind, N. 1975. Psychiatric conditions associated with focal lesions
of the central nervous system. In S. Arieti, & M. Reiser (Eds.), American handbook of
psychiatry, Vol 4. New York: Basic Books.
Biemond, A. 1970. Binswanger’s subcortical arteriosclerotic encephalopathy and the possibil-
ity of its clinical recognition. Psychiatria, Neurologia, Neurochirugia, 73, 413–417.
Bogousslavsky, J., Ferrazzini, M., Regli, F., Assal, G., Tanabe, H., & Delaloye-Bischof, A.
1988. Manic delirium and frontal lobe syndrome with paramedian infarction of the right
thalamus. Journal of Neurology, Neurosurgery, and Psychiatry, 51, 116–119.
Boone, K. B., Miller, B. L., Lesser, I. M., Mehringer, C. M., Hill-Gutierrez, E., Goldberg,
M. A., & Berman, N. G. 1992. Neuropsychological correlates of white-matter lesions in
healthy elderly subjects: A threshold effect. Archives of Neurology, 49, 549–554.
Burger, P. C., Burch, J. G., & Kunze, U. 1976. Subcortical arteriosclerotic encephalopathy
(Binswanger’s disease): A vascular etiology of dementia. Stroke, 7, 626–631.
Caplan, L. R., & Schoene, W. C. 1978. Clinical features of subcortical arteriosclerotic encepha-
lopathy (Binswanger’s disease). Neurology, 28, 1206–1215.
Corbett, A. J., McCusker, E. A., & Davidson, O. R. 1986. Acalculia following a dominant-
hemisphere subcortical infarct. Archives of Neurology, 43, 964–966.
Corbett, A. J., Bennett, H., & Kos, S. 1994. Cognitive dysfunction following subcortical in-
farction. Archives of Neurology, 51, 999–1007.
Cummings, J. L. 1993. Frontal-subcortical circuits and human behavior. Archives of Neurol-
ogy, 50, 873–880.
Cummings, J. L., & Benson, D. F. 1992. Dementia: A clinical approach. Boston: Butterworth-
Heinenmann.
Eslinger, P. J., Warner, G. C., Grattan, L. M., & Easton, J.D. 1991. ‘Frontal lobe’ utilization
behavior associated with paramedian thalamic infarction. Neurology, 41, 450–452.
280 MCPHERSON AND CUMMINGS

Fischer, P., Gatterer, G., Marterer, A., & Danielczyk, W. 1988. Nonspecificity of semantic
impairment in dementia of the Alzheimer’s type. Archives of Neurology, 45, 1341–
1343.
Fuld, P. A. 1981. The Fuld Object Memory Evaluation, Chicago: Stoelting Instruments.
Gainotti, G., Galtagirone, C., Masullo, C., & Miceli, G. 1980. Patterns of neuropsychologic
impairment in various diagnostic groups of dementia. In L. Amaducci, A. N. Davidson, &
P. Antuono (Eds.), Aging of the brain and dementia: Aging, Vol. 13, New York: Raven
Press.
Garcin, R., Lapresle, J., & Leon, G. 1960. Encéphalopathie sous-corticale chronique de Bins-
wanger: Etude anatomo-clinique de trois observations. Revue Neurologique, 102, 423–
440.
Gentilini, M., De Renzi, E., & Crisi, G. 1987. Bilateral paramedian thalamic artery infarcts:
Report of eight cases. Journal of Neurology, Neurosurgery, and Psychiatry, 50, 900–
909.
Geschwind, N. 1975. The apraxias: Neural mechanisms of disorders of learned movement.
American Scientist, 63, 188–195.
Goto, K., Ishii, N., & Fukasawa, H. 1981. Diffuse white-matter disease in the geriatric popula-
tion: A clinical, neuropathological, and CT study. Radiology, 141, 687–695.
Hemphill, R. E., & Klein, R. 1948. Contribution to the dressing disability as a focal sign and
to the imperception phenomena. Journal of Mental Science, 94, 611–622.
Hier, D. B., Hagenlocker, K., & Schindler, A. G. 1985. Language disintigration in dementia:
Effects of etiology and severity. Brain and Language, 25, 117–133.
Ishii, N., Nishihara, Y., & Imamura, T. 1986. Why do frontal lobe symptoms predominate in
vascular dementia with lacunes? Neurology, 36, 340–345.
Kertesz, A., & Clydesdale, S. 1994. Neuropsychological deficits in vascular dementia versus
Alzheimer’s disease. Archives of Neurology, 51, 1226–1231.
Kontiola, P., Laaksonen, R., Sulkava, R., & Erkinjuntti, T. 1990. Pattern of language impair-
ment is different in Alzheimer’s disease and multi-infarct dementia. Brain and Language,
38, 364–383.
Kurtzke, J. F. 1985. Epidemiology of cerebrovascular disease. In F. H. McDowell & L. R.
Kaplan (Eds.), Cerebrovascular survey report for the National Institute of Neurological
Disorders and Stroke. Bethesda, MD: National Institutes of Health.
LaRue, A. 1989. Patterns of performance on the Fuld Object Memory Evaluation in elderly
inpatients. Journal of Clinical and Experimental Neuropsychology, 11, 409–422.
LaRue, A. 1992. Aging and neuropsychological assessment. New York: Plenum.
Libon, D. J., Scanlon, M., Swenson, R., & Coslet, H. B. 1990. Binswanger’s disease: Some
neuropsychological considerations. Journal of Geriatric Psychiatry and Neurology, 3,
31–40.
Loizou, L. A., Kendall, B. E., & Marshall, J. 1981. Subcortical arteriosclerotic encephalopathy:
A clinical and radiological investigation. Journal of Neurology, Neurosurgery, and Psy-
chiatry, 44, 294–304.
Loewenstein, D. A., D’Elia, L., Guterman, A., Eisdorfer, C., Wilkie, F., LaRue, A., Mintzer,
J., & Duara, R. 1991. The occurrence of different intrusive errors in patients with Alzhei-
mer’s disease, multiple cerebral infarctions and major depression. Brain and Cognition,
16, 104–117.
Lotz, P. R., Ballinger, W. E., Jr., & Quisling, R. G. 1986. Subcortical arteriosclerotic encepha-
lopathy: CT spectrum and pathologic correlation. American Journal of Roentgenology,
147, 1209–1214.
Mendez, M. F., Adams, N. L., & Lewandowski, K. S. 1989. Neurobehavioral changes associ-
ated with caudate lesions. Neurology, 39, 349–354.
Mennemeier, M., Fennell, E., Valenstein, E., & Heilman, K. M. 1992. Contributions of the
left intralaminar and medial thalamic nuclei to memory. Comparisons and report of a
case. Archives of Neurology, 49, 1050–1058.
Mirsen, T., & Hachinski, V. 1988. Epidemiology and classification of vascular and multi-
 VASCULAR DEMENTIA 281

infarct dementia. In J. S. Meyer, H. Lechner, J. Marshall, & J. F. Toole (Eds.), Vascular

and Multi-infarct Dementia. Mount Kisko, NY: Future Publishing.
Nichols, F. T., III, & Mohr, J. P. 1986. Binswanger’s subacute arteriosclerotic encephalopathy.
In H. J. M. Barnett, J. P. Mohr, B. M. Stein, et al. (Eds.), Stroke: Pathophysiology, diagno-
sis, and management. New York: Churchill Livingstone Inc.
Oberg, R. G. E., & Divac, I. 1979. Cognitive functions of the neostriatum. In I. Divac &
R. G. E. Oberg (Eds.), The Neostriatum. New York: Pergamon.
Pepin, E. P., & Pepin, A. P. 1993. Selective dorsolateral frontal lobe dysfunction associated
with diencephalic amnesia. Neurology, 43, 733–741.
Perez, F. I., Rivera, V. M., Meyer, J. S., Gay, J. R. A., Taylor, R. L., & Mathew, N. T. 1975.
Analysis of intellectual and cognitive performance in patients with multi-infarct dementia,
vertebrobasilar insufficiency with dementia and Alzheimer’s disease. Journal of Neurol-
ogy, Neurosurgery, & Psychiatry, 38, 533–540.
Powell, A. L., Cummings, J. L., Hill, M. A., & Benson, D. F. 1988. Speech and language
alterations in multi-infarct dementia. Neurology, 38, 717–719.
Rao, S. M., Mittenberg, W., Bernardin, L., Haughton, V., & Leo, G. J. 1989. Neuropsychologi-
cal test findings on subjects with leukoariosis. Archives of Neurology, 46, 40–47.
Rocca, W. A., Hofman, A., Brayne, C., Breteler, M. M. B., Clarke, M., Copeland, J. R. M.,
Dartigues, J-F., Engedal, K., Hagnell, O., Heeren, T. J., Jonker, C., Lindesay, J., Lobo,
A., Mann, A. H., Mölsä, P. K., Morgan, K., O’Connor, D. W., da Silva Droux, A., Sulkava,
R., Kay, D. W. K., & Amaducci, L. 1991. The prevalence of vascular dementia in Europe:
Facts and fragments from 1980–1990 studies. Annals of Neurology, 30, 817–824.
Roman, G. C. 1985. Lacunar dementia. In J. T. Hutton & A. D. Kenny (Eds.), Senile dementia
of the Alzheimer type. New York: Alan R. Liss.
Roman, G. C. 1987. Senile dementia of the Binswanger type: A vascular form of dementia
in the elderly. Journal of the American Medical Association, 258, 1782–1788.
Roman, G. C. 1991. The epidemiology of vascular dementia. In A. Hartmann, W. Kuschin-
sky, & S. Hoyer (Eds.), Cerebral ischemia and dementia. Berlin: Springer-Verlag.
Roman, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H.,
Amaducci, L., Orgogozo, J. M., Brun, A., Hofman, A., Moody, D. M., O’Brien, M. D.,
Yamaguchi, T., Grafman, J., Drayer, B. P., Bennett, D. A., Fisher, M., Ogata, J., Kokmen,
E., Bermejo, F., Wolf, P. A., Gorelick, P. B., Bick, K. L., Pajeau, A. K., Bell, M. A.,
DeCarli, C., Culebras, A., Korczyn, A. D., Bogoussalavsky, J., Hartmann, A., & Scheinb-
erg, P. 1993. Vascular dementia: Diagnostic criteria for research studies. Neurology, 43,
250–260.
Ross, E. D. 1981. The aprosodias. Archives of Neurology, 38, 561–569.
Sandson, T. A., Daffner, K. R., Carvalho, P. A., & Mesulam, M. M. 1991. Frontal lobe dys-
function following infarction of the left-sided medial thalamus. Archives of Neurology,
48, 1300–1303.
Shindler, A. G., Caplan, L. R., & Hier, D. B. 1984. Intrusions and perseverations. Brain and
Language, 23, 148–158.
Steingart, A., Hachinski, V., Lau, C., Fox, A. J., Diaz, F., Cape, R., Lee, D., Inzitari, D., &
Merskey, H. 1987a. Cognitive and neurological findings in demented patients with diffuse
white matter lucencies on CT scan (leuko-araiosis). Archives of Neurology, 44, 32–35.
Steingart, A., Hachinski, V., Lau, C., Fox, A. J., Diaz, F., Cape, R., Lee, D., Inzitari, D., &
Merskey, H. 1987b. Cognitive and neurological findings in demented patients with diffuse
white matter lucencies on CT scan (leuko-araiosis). Archives of Neurology, 44, 36–39.
Strub, R. L. 1989. Frontal lobe syndrome in a patient with bilateral globus pallidus lesions.
Archives of Neurology, 46, 1024–1027.
Stuss, D. T., Guberman, A., Nelson, R., & Larochelle, S. 1988. The neuropsychology of par-
amedian thalamic infarction. Brain and Cognition, 8, 348–378.
Suzuki, K., Kutsuzawa, T., Nakajinia, K., & Hatano, S. 1991. Epidemiology of vascular de-
mentia and stroke in Akita, Japan. In A. Hartmann, W. Kuschinsky, & S. Hoyer (Eds.),
Cerebral ischemia and dementia. Berlin: Springer-Verlag.
282 MCPHERSON AND CUMMINGS

Tatemichi, T. K., Desmond, D. W., & Mayeux, R. 1992. Dementia after stroke: Baseline
frequency, risks, and clinical features in a hospitalized cohort. Neurology, 42, 1185–1193.
Tomonaga, M., Yamanouchi, H., Tohgi, H., & Kemeyama, M. 1982. Clinicopathologic study
of progressive subcortical vascular encephalopathy (Binswanger type) in the elderly. Jour-
nal of the American Geriatric Society, 39, 524–529.
Wolfe, N., Linn, R., Babikian, V. L., & Albert, M. L. 1990. Frontal systems impairment
following multiple lacunar infarcts. Archives of Neurology, 47, 129–132.
Yamaguchi, T., Ogata, J., & Yoshida, F. 1992. Epidemiology of vascular dementia in Japan.
Proceedings of the NINDS-AIREN International Workshop on Vascular Dementia. NIH,
Bethesda, MD April 19–21. New Issues in the Neurosciences 4.