Review
Stroke, cognitive deficits, and rehabilitation: still an incomplete picture
Toby B. Cumming1*, Randolph S. Marshall2, and Ronald M. Lazar2
Cognitive impairment after stroke is common and can cause
disability with major impacts on quality of life and indepen-
dence. There are also indirect effects of cognitive impairment
on functional recovery after stroke through reduced participa-
tion in rehabilitation and poor adherence to treatment guide-
lines. In this article, we attempt to establish the following:
whether there is a distinct profile of cognitive impairment
after stroke; whether the type of cognitive deficit can be
associated with the features of stroke-related damage; and
whether interventions can improve poststroke cognitive per-
formance. There is not a consistent profile of cognitive deficits
in stroke, though slowed information processing and execu-
tive dysfunction tend to predominate. Our understanding of
structurefunction relationships has been advanced using
imaging techniques such as lesion mapping and will
be further enhanced through better characterization of
damage to functional networks and identification of subtle
white matter abnormalities. Effective cognitive rehabilitation
approaches have been reported for focal cortical deficits
such as neglect and aphasia, but treatments for more diffu-
sely represented cognitive impairment remain elusive. In the
future, the hope is that different techniques that have been
shown to promote neural plasticity (e.g., exercise, brain stimu-
lation, and pharmacological agents) can be applied to improve
the cognitive function of stroke survivors.
Key words: cerebrovascular disease, cognitive impairment,
neuropsychology, rehabilitation, stroke
Introduction
To reduce the cognitive fallout from stroke, we must be able to
characterize abnormalities in cognition, understand the underly-
ing causes of cognitive impairment, and determine the efficacy of
different treatment and rehabilitation approaches. In this review,
we will mostly confine ourselves to clinically apparent stroke but
will discuss some evidence from studies of asymptomatic cere-
brovascular disease and white matter changes.
Defining cognitive impairment
Cognition is not a unitary concept; it incorporates multiple
domains, including attention (focusing, shifting, dividing, or
sustaining attention on a particular stimulus or task), executive
function (planning, organizing thoughts, inhibition, control),
visuospatial ability (visual search, drawing, construction),
memory (recall and recognition of visual and verbal informa-
tion), and language (expressive and receptive). Classification is
far from straightforward, as domains are not independent for
Correspondence: Toby B. Cumming*, Florey Neuroscience Institutes,
245 Burgundy St, Heidelberg, Melbourne, Vic. 3084, Australia.
E-mail: tcumming@unimelb.edu.au
1
Stroke Division, Florey Neuroscience Institutes, Melbourne, Vic.,
Australia
2
Department of Neurology, Columbia University Medical Center,
New York, NY, USA
DOI: 10.1111/j.1747-4949.2012.00972.x
38 Vol 8, January 2013, 3845
example, remembering a list of grocery items you have been told
to buy is not just reliant on memory but also on attention and
language. What constitutes a cognitive domain is unclear, with the
following dimensions often incorporated: neglect (inattention to
one side of space), agnosia (failure in object recognition), apraxia
(disordered motor planning), abstract thinking (ability to use
higher-order semantic information), and arithmetic. It is impor-
tant to recognize the effects that different states of physiology and
mood (e.g., fatigue, apathy, depression) can have on cognition,
though these factors will not be reviewed here as they are modi-
fiers rather than components of cognition. The accepted gold
standard for determining cognitive abnormality is a battery of
neuropsychological tests covering various domains, with norma-
tive information used to indicate domain-specific deficits. Our
focus will be on cognitive impairment, which includes the milder
end of the cognitive dysfunction spectrum and not the more
disabling dementia. In an Alzheimer-dominated landscape, the
term dementia has become amnestically loaded, with a dementia
diagnosis requiring memory impairment. Yet memory dysfunc-
tion is often not the most pronounced feature after stroke; only
about half of those with vascular cognitive impairment exhibit
amnestic signs (1). A more useful framework for classifying post-
stroke cognitive deficits emphasizes cognitive impairment rather
than dementia (2). This classification, though, still entails reduc-
ing rich information gained from multiple cognitive assessments
down to a coarse dichotomy. Ideally, we want detailed informa-
tion on performance across various cognitive tasks, thus allowing
insight into the severity of and interrelationships among deficits
in different domains.
Is there a distinct profile of cognitive impairment
arising from stroke?
There is a substantial literature on domain-specific cognitive
function after stroke. In an influential 1994 study, Tatemichi and
colleagues identified a generalized profile of cognitive problems
across all domains. Attention, memory, language, and orientation
were most affected by stroke, yet patients also had marked deficits
in visuospatial skills and abstract reasoning (3). In 1998, a large
European study yielded a similarly diffuse poststroke cognitive
profile. Tasks of attention, visuospatial ability, and verbal fluency
were the most affected, but language and memory performance
was also down (4). It is now thought that stroke tends to have
greater deleterious impact on attention and executive function
than on memory, but such a profile was not evident in these early
studies. A possible explanation relates to experimental design. The
above two studies compared hospital-based stroke patients with
healthy volunteer controls and thus may have overestimated post-
stroke cognitive impairments, diminishing any domain-specific
differences. In a community-based comparison of stroke patients
with population controls, results fit more closely with current
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 T. B. Cumming et al.
thinking. Patients were more frequently impaired than controls
in spatial ability, executive function, attention, and language but
were not more impaired in orientation or memory (5). Other
studies have reinforced the view that stroke-related cognitive
problems are weighted more toward attention-executive dysfunc-
tion than memory dysfunction. Marked deficits in abstraction,
executive function, and processing speed have been reported
(6). Population-based evidence suggests that a history of stroke
is associated with a higher risk of nonamnestic [odds ratio
(OR) = 285] than amnestic (OR = 177) cognitive impairment
and is associated with every cognitive domain except memory (7).
Contributing evidence comes not only from stroke but from
studies of other vascular changes. In a cohort of 164 Catholic
nuns, priests, and brothers, the presence of one or more silent
infarcts on autopsy was related most strongly with perceptual
speed and least strongly with episodic memory (8). Magnetic
resonance imaging (MRI) data from elderly participants in the
LADIS study indicated that the appearance of new lacunes is
associated with decline in executive function and processing
speed but not memory (9).
Speed of processing
Cognitive slowing is a common complaint after stroke, and a
majority of patients exhibit marked slowness of information pro-
cessing (4,10). Processing speed is clinically relevant, as it makes
an independent contribution to functional outcome after stroke
(11) and is independently predictive of dependency in stroke
survivors (12). While not typically considered a stand-alone
domain, processing speed has a major influence on cognitive
performance. Importantly, this influence is not consistent across
different cognitive domains. It is possible that attention and
executive deficits appear to predominate after stroke because
these domains are more often tested using time-sensitive tasks
(e.g., Trail-Making and verbal fluency) than the domains of
memory or language. There is evidence to support this: when the
block design task from the Wechsler Adult Intelligence Scale
(WAIS) was time limited, 47% of stroke patients performed
beyond two standard deviations below the control mean, com-
pared with only 24% when there was no time limit (4). We
contend that the typical poststroke cognitive profile should
include deficits in processing speed alongside deficits in attention
and executive function. The prominence of these domains
appears to be unaffected by the length of time since stroke. In
acute stroke, disorders in executive function were found to be
particularly prevalent (13). At one year poststroke, a majority of
patients still had attention deficits, while deficits in language and
memory were more likely to have resolved (14). At five years
poststroke, deficits were more pronounced in processing speed
(z = -216) and executive function (z = -192) than in visual
memory (z = -043) and verbal memory (z = -032) (11).
Memory function
Identifying the extent to which memory is compromised after
stroke can be difficult. Ballard et al. (15) concluded that impair-
ments of processing speed, attention, and executive function were
the most pronounced after stroke, but the exclusion of patients
with dementia meant memory impairment was unlikely to be
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International Journal of Stroke 2012 World Stroke Organization
Review
prominent. Early studies on multi-infarct or vascular dementia
focused on differentiating these entities from Alzheimers disease.
Data typically showed that vascular dementia patients had supe-
rior long-term memory but more frontal executive impairment
than Alzheimer patients (16). It is important to recognize,
though, that such results do not imply spared memory in the
vascular patients. More direct evidence for this sparing is the
finding that memory performance of patients with cerebrovascu-
lar disease was much closer to a healthy elderly profile than an
Alzheimer profile (17). Of course, memory problems can mani-
fest following stroke. The five-year progression of vascular cogni-
tive impairment has been shown to include memory deficits (18).
The presence of sub-cortical infarcts in older people has been
associated with lower episodic, semantic, and working memory
performance (19). Memory deficits, though, appear to be less
prevalent than deficits in other cognitive domains, and when they
do occur, they are likely to have a different genesis to those seen in
Alzheimer patients. Recognition memory, which tests retention of
information without effortful search and retrieval, may be less
affected than noncued recall after stroke (4,6), suggesting that the
underlying cause may be less amnestic and more executive.
Are stroke characteristics associated with the
profile of cognitive deficits?
Many studies into this question rely on correlative evidence, asso-
ciating stroke features and cognitive status in large cohorts. Early
research indicated that cognitive impairment was most frequent
after left anterior and posterior cerebral artery infarcts, and less
frequent after vertebrobasilar artery infarcts (3). Others have
found that infarcts in the middle cerebral artery (MCA) are asso-
ciated with greater likelihood of cognitive impairment (20).
Stroke in cortical regions increases the likelihood of cognitive
dysfunction. In the acute stage of stroke, cognitive impairments
were detected in 74% of patients with cortical stroke but in less
than 50% of those with sub-cortical or infratentorial stroke (13).
Stroke etiology also plays a part in cognitive outcome: cortical
deficits such as aphasia and neglect were more common after
cardioembolic stroke than either large-vessel or small-vessel
disease stroke (21).
In terms of more general stroke characteristics, a meta-analysis
identified haemorrhagic stroke, left hemisphere involvement,
and recurrence as the factors that predicted subsequent dementia
(22). Haemorrhagic stroke has been independently associated
with cognitive deficits across multiple domains (13). Lesions tend
to be larger in cognitively impaired patients than in nonimpaired
patients (27 vs. 9 cm3) (13), but this is neither surprising nor
particularly informative as larger strokes are more likely to
encroach upon cortical and other regions that support cognition.
Left hemisphere bias in cognitive impairment is a common
finding, though the reliance of many neuropsychological tasks on
language ability is a confounding factor. Stroke recurrence has
been linked to cognitive decline and was independently associated
with incident dementia at two-year follow-up (23). In terms of
cognitive prognosis, lesion location was a useful predictor of
domain-specific recovery, but lesion volume was an independent
Vol 8, January 2013, 3845 39
 Review
predictor of recovery only in visual memory (24). Other studies
have shown that lesion volume, while correlated with initial
aphasia severity, was not associated with recovery in language
(25,26). The impact of lesion laterality on cognitive recovery is
unclear, with examples of right hemispheric superiority (27), left
hemispheric superiority (28), and no difference (24).
Aphasia and neglect
In clinical practice, two of the most prominent focal cognitive
deficits after stroke are aphasia and hemispatial neglect (29). The
relationship between type of aphasia or neglect and location of
infarction is well described. The limitation to spoken output that
is characteristic of Brocas aphasia is associated with damage
in the left posterior, inferior frontal gyrus, in addition to other
regions supplied by the upper division of the left middle cerebral
artery (30). Wernickes aphasia, on the other hand, is character-
ized by fluent but relatively meaningless speech alongside poor
language comprehension and is linked to damage in the left
posterior, superior temporal gyrus (30). In hemispatial neglect,
the visuospatial component is linked to the right inferior parietal
lobule, the visuomotor component to the right dorsolateral
prefrontal cortex, and the object-centered component to the deep
temporal lobe regions (31). Structurefunction evidence of this
kind is often derived from lesion mapping, where lesions from a
group of stroke patients with a particular cognitive deficit can be
superimposed to determine the area of greatest overlap. This
powerful technique employs group data while accounting for
individual variability in brain structure. The problem is that while
the mapping approach can work well for focal syndromes associ-
ated with lesions in circumscribed areas, more complex cognitive
deficits such as executive dysfunction involve more widely distrib-
uted injury and more likely a broad network. Neuropsychological
(32) and functional imaging (33) evidence indicates that execu-
tive processes are not limited to the frontal lobes but are sub-
served by a distributed network of cortical, sub-cortical, and
infratentorial areas. Even in the case of neglect, it has been argued
that dysfunction of distributed cortical networks for attention
provides a better account than structural damage to specific
regions (34).
Diffuse neuronal dysfunction
There is a broad distinction between focal damage, which can lead
to selective cognitive impairments, and diffuse neuronal dysfunc-
tion, which produces a more uniform profile of mental slow-
ing, memory problems, and executive deficits (35). Clouding the
picture is the observation that certain strategic infarcts (e.g., genu
of the internal capsule) can produce what clinically appears to be
a diffuse cognitive syndrome (36). Diffuse dysfunction typically
results from underlying sub-clinical cerebrovascular disease, such
as white matter disease, or an accumulation of small infarcts as in
small-vessel disease (37). Over the four years following stroke,
higher load of white matter hyperintensities (WMHs) is strongly
associated with dementia and cognitive decline (38). Stroke
patients with white matter lesions and silent infarcts were worse
on cognitive tasks at baseline and two-year follow-up than those
without this damage (39).
40 Vol 8, January 2013, 3845
T. B. Cumming et al.
Though the damage is diffuse, it may be possible to identify
some regional specificity in the relationship between white matter
abnormalities and cognition. Slowed processing and attentional
and executive impairments have been associated with the severity
of WMHs in the internal capsule, caudate, and thalamus of stroke
patients (40). Lesions in these areas disrupt fronto-striato-
thalamic circuits and thus impact upon dorsolateral prefrontal
cortex and anterior cingulate, regions known to support attention
and executive function. Cognitive impairment has been corre-
lated with WMHs in the frontal lobes and internal capsule,
with hyperintense lesions in the basal ganglia and thalamus
most closely associated with neuropsychological performance
(6). Others have found that, while WMHs were associated with
reduced mental speed, executive function, memory, and visuo-
spatial ability, regional correlation was relatively weak (41). The
impact of small-vessel disease is not restricted to stroke: incidence
of new lacunes in an elderly population has been linked to decline
in executive function and processing speed (9).
Advanced imaging techniques, such as diffusion tensor imaging
(DTI), can identify subtle abnormalities in axonal function that
may be a marker for generalized cognitive impairment. Calculat-
ing functional anisotropy from DTI scans provides a metric for
the integrity of white matter structures, with lower anisotropy
reflecting greater diffusivity. Lower anisotropy has been identified
in those with vascular cognitive impairment, even in regions
without visible white matter abnormalities on conventional MRI
(42). In ischemic stroke patients, cognition appears more closely
associated with anisotropy in frontal and parietal regions than in
occipital and temporal areas (43). We know that predicting cog-
nitive outcome using the features of a focal lesion is imperfect;
DTI offers the promise of increased explanatory power by deter-
mining the effects of altered connectivity between brain regions.
Hypoperfusion
Compromised blood flow is relevant to both focal and diffuse
deficits. In ischemic stroke, focal cognitive deficits arise not just
from the infarction itself but also from hypoperfusion in adjacent
tissue. In the acute setting, aphasia and neglect are more closely
associated with the volume of peri-infarct perfusion failure than
the infarct itself (44). White matter hyperintensities, thought to
represent incomplete infarction, have been attributed to transient
decreases in cerebral blood flow (45). At the whole-brain level, the
dynamic nature of information processing, attention, and working
memory may be uniquely susceptible to dynamic changes in blood
flow across widely distributed brain regions (46).
Perhaps the clearest evidence for a cerebral hemodynamic
effect is in large-vessel disease, where loss of perfusion pressure
to a cerebral hemisphere supplied by a blocked carotid artery
induces a series of hemodynamic responses, including dilation of
cerebral arterioles and increase of oxygen extraction fraction.
TIA patients with recently symptomatic carotid artery occlusion
who had single-hemisphere cerebral hypoperfusion had greater
cognitive impairment than those without this hypoperfusion
(47). Hypoperfusion may also impact cognition through reduc-
tions in brain volume. Gray matter volume reductions have been
identified in cognitively impaired ischemic stroke patients,
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 T. B. Cumming et al.
predominantly in the thalamus (48). With abnormalities in gray
matter unrelated to the site of infarction, generalized hypo-
perfusion is a plausible mechanism.
Cardiac research also supports the idea of hypoperfusion-
related cognitive dysfunction. Patients with global hemodynamic
compromise arising from congestive heart failure have deficits
in distributed processing skills, including attention, executive
function, and memory (49). In older patients with heart failure,
memory performance was worse in those with lower left ventricu-
lar ejection fraction (<30%) (50). Again, brain volume changes
are potentially relevant; cognitive deficits arising from ischemic
heart disease may be a result of reduced cerebral gray matter (51).
Sub-cortical stroke
Historically, damage to the cerebellum has been associated
with disorders of motor coordination. While cerebellar stroke is
unlikely to cause the classic cortical signs of aphasia or neglect
(52), this does not mean the cerebellum is uninvolved in cognition
(53). Groups of patients with cerebellar damage, mostly with
stroke etiology, have been shown to have deficits in visuospatial
ability (54), verbal working memory (55), and across multiple
domains including executive function and abstract reasoning
(56). There are anatomical grounds for expecting the cerebellum
to play a role in cognition. While the cerebellum is a structurally
distinct brain region, it is linked by neuronal circuits within the
brain stem and has many projections toward associative brain
areas (57). Stroke in the basal ganglia can produce cognitive dys-
function. In a group of 12 patients with stroke confined to the
basal ganglia, significant abnormalities were found in all domains
tested (memory, attention, visuospatial, and language), though
individual profiles were not presented (58). The importance of the
thalamus to cognition has been well documented. In a study of 10
patients with isolated thalamic lesions, deficits in long-term
memory, executive function, and attention were associated with
specific areas of the thalamus (59). The thalamus is a good illus-
tration of why lesion size is not everything small but strategically
placed lesions here can lead to severe cognitive impairments (60).
Neuropsychological assessment
Increased knowledge of structurefunction relationships can
inform our approach to neuropsychological assessment. There is
now sufficient experience in different aspects of cerebrovascular
disease that a long, comprehensive battery may not be necessary;
rather, a tailored approach based on the nature of the disease (e.g.,
branch occlusion, carotid artery stenosis, and small-vessel
disease) can be both clinically meaningful and cost effective
(47,61). Of greatest relevance is the neuropsychological delinea-
tion of suspected cortical signs. For example, a brief, targeted
neuropsychological assessment of cortical features such as
neglect, spatial processing, and visuoconstructional function in a
patient with a suspected right parietal stroke not only informs
clinical diagnosis but also aids clinical decision making. The pres-
ence of cortical signs provides information about the likely stroke
territory. This relates directly to probable stroke mechanism
which, in turn, affects the preferred choice of treatment.
A tailored assessment of this type can be particularly beneficial in
an acute stroke setting where patient fatigue and attentional limi-
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International Journal of Stroke 2012 World Stroke Organization
Review
tations often prevent lengthy, battery-type assessments. The fact
that repair mechanisms, such as resolution of possible perfusion
deficits (62), take their course in the days following stroke should
not necessarily preclude early assessment. In striatocapsular
stroke, for example, the cortical features that are diagnostic of this
stroke sub-type are best identified in the first few days, after which
they slowly resolve and become harder to detect. Timely charac-
terization of cognitive impairment provides valuable prognostic
information (24), assists in rehabilitation planning, and allows
therapies to be targeted to specific cognitive domains.
Are there rehabilitation approaches that improve
cognitive performance after stroke?
Reducing the impact of poststroke cognitive impairment is an
important goal. In addition to having a direct influence on the
quality of life of patients and their caregivers, cognitive impair-
ment after stroke is associated with higher mortality (63), greater
rates of institutionalization (64), and higher health-care costs
(65). Cognition is important for recovery in other neurological
domains patients with higher cognitive status on admission to
rehabilitation had better functional outcomes, even when relevant
confounders were controlled (66). Cognitive impairments can
reduce a persons ability to understand task instructions, to plan
and initiate self-directed activities, and to solve problem. The
executive function of stroke patients in inpatient rehabilitation
has been independently associated with the level of participation
in rehabilitation (67).
Approaches to improving cognitive outcome after stroke can be
classified as either compensatory or restorative. Compensatory
approaches involve adapting the external environment to altered
cognitive abilities. Characteristics of the external environment
that help or hinder cognitive performance were identified in the
Analysis of Cognitive Environmental Support tool (68). One spe-
cific external strategy that has been tested is an electronic paging
system. While found to be effective in compensating for everyday
memory and planning problems after brain injury (69), main-
taining these benefits over time may be difficult for stroke
survivors (70). Compensatory strategies can also be internally
generated. Rather than attempt to restore reaction time to a
normal speed, Winkens et al. (71) introduced a time pressure
management strategy: stroke patients were taught to compensate
for mental slowness in real-life tasks by reorganizing the execu-
tion of sub-tasks that had a time pressure component. Their
treatment group significantly outperformed controls on speed of
performance on everyday tasks at three-month follow-up. Other
cognitive rehabilitation approaches aim for the compelling goal of
direct restoration of function. The realization that neural plastic-
ity is present throughout life and can be influenced by training
has generated hope in this area, but conclusive studies remain
scarce. The strongest evidence of effectiveness is for treatment of
focal cortical deficits. A review of evidence-based cognitive reha-
bilitation identified substantial evidence for cognitive-linguistic
therapies to treat aphasia and for visuospatial rehabilitation
to treat neglect after stroke, but effective treatments in other
domains were lacking (72).
Vol 8, January 2013, 3845 41
 Review
Domain-specific interventions
Originally used in the context of upper extremity and motor
retraining after stroke, the principles of constraint-induced
therapy have been applied to aphasia. Constraint-induced treat-
ment protocols can improve functional communication in
chronic aphasia after stroke (73). There is also evidence that low-
frequency repetitive transcranial magnetic stimulation (rTMS)
can improve language abilities in patients with chronic nonfluent
aphasia. The theory is that the stimulation modulates and inhibits
overactivity in the right hemisphere homologous language sites,
such as the inferior frontal gyrus. Significant improvements
following rTMS have been reported in the picture naming
(74), expressive language and auditory comprehension (75), and
semantic fluency (76) of stroke patients with chronic aphasia.
In stroke patients with hemispatial neglect, using prism glasses
to create an optical shift of the visual field to the right has been
successful. The original 1998 study included patients in the first
year after stroke and revealed improvements in sensorimotor
and spatial function after a single prism adaptation (77). More
recent work has shown that prism adaptation also works in
chronic stroke. In patients who were one to seven years post-
stroke and had persistent neglect, an eight-week intervention
with prism glasses produced improved eye movements on the
neglected side and improved standing center of gravity (78).
Prism adaptation may actually be best suited to the sub-acute
and chronic stages of stroke when the nature of the neglect
deficit has been established. Prism adaptation in acute stroke
patients yielded some benefits on spatial tasks (line bisection and
cancellation), but these benefits were not maintained at one
month posttreatment (79). It is likely that much of the improve-
ment in both treatment and placebo control groups was due to
spontaneous recovery.
Cochrane reviews have revealed the paucity of studies in post-
stroke cognitive rehabilitation for both memory deficits (80) and
attention deficits (81). Unlike the example of constraint-based
therapy, the principles of task-specific training do not seem to
translate from motor rehabilitation to cognitive rehabilitation.
Repetition and rehearsal of the targeted cognitive task is insuffi-
cient to produce meaningful improvement. Results from one
small stroke study (n = 12) indicated that teaching mnemonic
strategies resulted in better memory performance, but improve-
ments did not generalize beyond the trained memory tasks (82).
In a small trial (n = 27), a computerized training program had
significant effects on alertness and sustained attention, but the
benefits did not generalize to other attentional and cognitive
functions (83). In the years since the Cochrane reviews, one of the
most promising studies was a randomized controlled trial of
attention process training in 78 stroke patients with attention
deficits (84). Postintervention change scores on the Integrated
Visual Auditory Continuous Performance Test were superior
in the treatment group, and this superiority was maintained at
six-month follow-up.
Interventions for generalized cognitive impairment
Hypertension is an obvious treatment target. In the PROGRESS
trial, active blood pressure lowering reduced the risk of cognitive
42 Vol 8, January 2013, 3845
T. B. Cumming et al.
decline (risk ratio = 19%), most likely by preventing the advance
of additional lacunar infarcts (85). This positive result, however,
was not reproduced in the PRoFESS trial, where treatment with
antiplatelet and antihypertensive therapy made no difference to
cognitive outcomes (86). Blood pressure control may also have a
downside, given the association between hypoperfusion and cog-
nitive performance. A quarter of a century ago, Meyer et al. (87)
followed 52 multi-infarct dementia patients over two years.
Among hypertensive patients, improved cognition was correlated
with systolic blood pressure control within upper normal limits
(135150 mmHg) and cognition worsened if blood pressure was
reduced below this level. As more direct evidence of this link, a
pilot study showed that cortical reperfusion with temporary
blood pressure increase for patients with large-vessel stenosis in
the acute stage resulted in improved cognition, both in the short
and longer terms (88).
Pharmacological agents can influence cognition. Normally
used to treat depression, escitalopram has been found to benefit
cognitive function in stroke patients (89). Compared with
patients who received placebo or problem solving therapy, those
receiving escitalopram had improved global cognition on the
RBANS (Repeatable Battery for the Assessment of Neuropsycho-
logical Status), particularly in memory. Rivastigmine, typically
used in Alzheimers disease, was tested in a randomized con-
trolled trial among stroke patients with cognitive impairment but
not dementia (90). The treatment group exhibited significantly
improved performance on verbal fluency for animals relative to
controls. The results of these two studies and the previously cited
study on attention process training (84), however, need to be
interpreted with caution until successfully replicated. All three
studies featured improvement in one or two cognitive measures in
the context of multiple other cognitive outcomes that were not
affected, and in each case there was an imbalance in baseline
performance between the groups.
Increasing physical activity is another potential treatment; it
has been shown to improve cognitive performance in the cogni-
tively impaired (91), those at risk of Alzheimers disease (92), and
patients with multiple sclerosis (93). Benefits seem to be greatest
in cognitive speed and attention (94) and executive control (95).
This is important as these central cognitive processes provide the
foundation for many other aspects of cognition. The relationship
between physical and mental activity may also apply to stroke
patients, but there is scant empirical evidence to date. In a recent
review, only 12 studies were identified that employed physical
activity interventions in stroke and had cognitive outcomes (96).
One of the few that had cognition as a primary focus found stroke
patients exposed to an eight-week exercise program had improved
information processing speed on a serial reaction time task
relative to control patients (97). Combining increased physical
activity with mental challenges, sensory stimulation, and social
interaction in an enriched environment may contribute to
improvements in cognition after stroke. Most of the current evi-
dence for this comes from animals (98), but there are data from
humans showing that listening to music early after stroke can
enhance cognitive recovery (99). Epidemiological studies have
demonstrated the cognitive value of interactions with other
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 T. B. Cumming et al.
people, using markers such as marital status and frequency of
social activities (100,101).
Conclusion
General patterns can be detected in the profile of cognitive
impairment after stroke: focal disorders such as aphasia and
neglect are common, as are more diffuse abnormalities such as
slowed information processing and executive dysfunction. Lesion
mapping studies have been helpful in delineating the brain areas
that contribute to domain-specific cognitive processes, and new
research into how structural damage affects functional networks
will further increase our understanding. Determining the causes
of diffusely represented cognitive deficits is difficult but may well
be related to sub-clinical vascular changes and subtle abnormali-
ties in white matter; such factors are starting to be revealed by
new imaging techniques. Cognitive rehabilitation approaches
have been relatively successful for focal cortical deficits but less so
for more generalized cognitive impairment. Repetitive transcra-
nial magnetic stimulation and prism adaptation are two very
different techniques to manipulate neural activity and drive plas-
ticity. Further studies are needed to test other ways of stimulating
functional brain changes after stroke to improve cognition.
Acknowledgements
We thank Dr Jennifer Bradshaw for her valuable contribution to
the section on neuropsychological assessment. Dr Cumming is
funded by a National Heart Foundation Postdoctoral Research
Fellowship. The Florey Neuroscience Institutes acknowledges
strong support from the Victorian Government and in particular
the funding from the Operational Infrastructure Support Grant.
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