Review

Stroke, cognitive decits, 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 independence. There are also indirect effects of cognitive impairment on functional recovery after stroke through reduced participation in rehabilitation and poor adherence to treatment guidelines. In this article, we attempt to establish the following: whether there is a distinct prole of cognitive impairment after stroke; whether the type of cognitive decit can be associated with the features of stroke-related damage; and whether interventions can improve poststroke cognitive performance. There is not a consistent prole of cognitive decits in stroke, though slowed information processing and executive 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 identication of subtle white matter abnormalities. Effective cognitive rehabilitation approaches have been reported for focal cortical decits such as neglect and aphasia, but treatments for more diffusely 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 stimulation, 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 underlying causes of cognitive impairment, and determine the efcacy of different treatment and rehabilitation approaches. In this review, we will mostly conne ourselves to clinically apparent stroke but will discuss some evidence from studies of asymptomatic cerebrovascular disease and white matter changes.

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 important 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 modiers rather than components of cognition. The accepted gold standard for determining cognitive abnormality is a battery of neuropsychological tests covering various domains, with normative information used to indicate domain-specic decits. 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 dysfunction 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 poststroke cognitive decits emphasizes cognitive impairment rather than dementia (2). This classication, though, still entails reducing rich information gained from multiple cognitive assessments down to a coarse dichotomy. Ideally, we want detailed information on performance across various cognitive tasks, thus allowing insight into the severity of and interrelationships among decits in different domains.

Is there a distinct prole of cognitive impairment arising from stroke?

There is a substantial literature on domain-specic cognitive function after stroke. In an inuential 1994 study, Tatemichi and colleagues identied a generalized prole of cognitive problems across all domains. Attention, memory, language, and orientation were most affected by stroke, yet patients also had marked decits in visuospatial skills and abstract reasoning (3). In 1998, a large European study yielded a similarly diffuse poststroke cognitive prole. Tasks of attention, visuospatial ability, and verbal uency 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 prole 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 poststroke cognitive impairments, diminishing any domain-specic differences. In a community-based comparison of stroke patients with population controls, results t more closely with current
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Dening 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 information), and language (expressive and receptive). Classication 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

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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 dysfunction than memory dysfunction. Marked decits 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 processing (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 inuence on cognitive performance. Importantly, this inuence is not consistent across different cognitive domains. It is possible that attention and executive decits appear to predominate after stroke because these domains are more often tested using time-sensitive tasks (e.g., Trail-Making and verbal uency) 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, compared with only 24% when there was no time limit (4). We contend that the typical poststroke cognitive prole should include decits in processing speed alongside decits 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 decits, while decits in language and memory were more likely to have resolved (14). At ve years poststroke, decits 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 difcult. Ballard et al. (15) concluded that impairments 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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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 superior 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 nding that memory performance of patients with cerebrovascular disease was much closer to a healthy elderly prole than an Alzheimer prole (17). Of course, memory problems can manifest following stroke. The ve-year progression of vascular cognitive impairment has been shown to include memory decits (18). The presence of sub-cortical infarcts in older people has been associated with lower episodic, semantic, and working memory performance (19). Memory decits, though, appear to be less prevalent than decits 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 prole of cognitive decits?

Many studies into this question rely on correlative evidence, associating 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 associated 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 decits 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 identied haemorrhagic stroke, left hemisphere involvement, and recurrence as the factors that predicted subsequent dementia (22). Haemorrhagic stroke has been independently associated with cognitive decits 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 nding, 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-specic recovery, but lesion volume was an independent
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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 decits 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 characterized by uent 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 decit 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 associated with lesions in circumscribed areas, more complex cognitive decits such as executive dysfunction involve more widely distributed injury and more likely a broad network. Neuropsychological (32) and functional imaging (33) evidence indicates that executive processes are not limited to the frontal lobes but are subserved 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 specic regions (34). Diffuse neuronal dysfunction There is a broad distinction between focal damage, which can lead to selective cognitive impairments, and diffuse neuronal dysfunction, which produces a more uniform prole of mental slowing, memory problems, and executive decits (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).

T. B. Cumming et al. Though the damage is diffuse, it may be possible to identify some regional specicity 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-striatothalamic circuits and thus impact upon dorsolateral prefrontal cortex and anterior cingulate, regions known to support attention and executive function. Cognitive impairment has been correlated 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 visuospatial 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. Calculating functional anisotropy from DTI scans provides a metric for the integrity of white matter structures, with lower anisotropy reecting greater diffusivity. Lower anisotropy has been identied 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 cognitive outcome using the features of a focal lesion is imperfect; DTI offers the promise of increased explanatory power by determining the effects of altered connectivity between brain regions. Hypoperfusion Compromised blood ow is relevant to both focal and diffuse decits. In ischemic stroke, focal cognitive decits 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 ow (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 ow 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 reductions in brain volume. Gray matter volume reductions have been identied 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 hypoperfusion is a plausible mechanism. Cardiac research also supports the idea of hypoperfusionrelated cognitive dysfunction. Patients with global hemodynamic compromise arising from congestive heart failure have decits 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 ventricular ejection fraction (<30%) (50). Again, brain volume changes are potentially relevant; cognitive decits 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 decits 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 dysfunction. In a group of 12 patients with stroke conned to the basal ganglia, signicant abnormalities were found in all domains tested (memory, attention, visuospatial, and language), though individual proles 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, decits in long-term memory, executive function, and attention were associated with specic areas of the thalamus (59). The thalamus is a good illustration 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 sufcient 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 delineation 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 presence 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 benecial in an acute stroke setting where patient fatigue and attentional limi 2012 The Authors. 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 decits (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 identied in the rst few days, after which they slowly resolve and become harder to detect. Timely characterization of cognitive impairment provides valuable prognostic information (24), assists in rehabilitation planning, and allows therapies to be targeted to specic 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 inuence on the quality of life of patients and their caregivers, cognitive impairment 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 classied 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 identied in the Analysis of Cognitive Environmental Support tool (68). One specic 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), maintaining these benets over time may be difcult 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 execution of sub-tasks that had a time pressure component. Their treatment group signicantly 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 plasticity is present throughout life and can be inuenced by training has generated hope in this area, but conclusive studies remain scarce. The strongest evidence of effectiveness is for treatment of focal cortical decits. A review of evidence-based cognitive rehabilitation identied 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).
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Domain-specic 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 treatment protocols can improve functional communication in chronic aphasia after stroke (73). There is also evidence that lowfrequency repetitive transcranial magnetic stimulation (rTMS) can improve language abilities in patients with chronic nonuent aphasia. The theory is that the stimulation modulates and inhibits overactivity in the right hemisphere homologous language sites, such as the inferior frontal gyrus. Signicant improvements following rTMS have been reported in the picture naming (74), expressive language and auditory comprehension (75), and semantic uency (76) of stroke patients with chronic aphasia. In stroke patients with hemispatial neglect, using prism glasses to create an optical shift of the visual eld to the right has been successful. The original 1998 study included patients in the rst 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 poststroke 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 decit has been established. Prism adaptation in acute stroke patients yielded some benets on spatial tasks (line bisection and cancellation), but these benets were not maintained at one month posttreatment (79). It is likely that much of the improvement in both treatment and placebo control groups was due to spontaneous recovery. Cochrane reviews have revealed the paucity of studies in poststroke cognitive rehabilitation for both memory decits (80) and attention decits (81). Unlike the example of constraint-based therapy, the principles of task-specic training do not seem to translate from motor rehabilitation to cognitive rehabilitation. Repetition and rehearsal of the targeted cognitive task is insufcient to produce meaningful improvement. Results from one small stroke study (n = 12) indicated that teaching mnemonic strategies resulted in better memory performance, but improvements did not generalize beyond the trained memory tasks (82). In a small trial (n = 27), a computerized training program had signicant effects on alertness and sustained attention, but the benets 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 decits (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

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 cognitive 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 inuence cognition. Normally used to treat depression, escitalopram has been found to benet 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 Neuropsychological Status), particularly in memory. Rivastigmine, typically used in Alzheimers disease, was tested in a randomized controlled trial among stroke patients with cognitive impairment but not dementia (90). The treatment group exhibited signicantly improved performance on verbal uency 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 cognitively impaired (91), those at risk of Alzheimers disease (92), and patients with multiple sclerosis (93). Benets 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 identied 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 evidence 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).

Review
8 Schneider JA, Wilson RS, Cochran EJ et al. Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 2003; 60:10828. 9 Jokinen H, Gouw AA, Madureira S et al. Incident lacunes inuence cognitive decline. Neurology 2011; 76:18728. 10 Rasquin S, Lodder J, Verhey F. The association between psychiatric and cognitive symptoms after stroke: a prospective study. Cerebrovasc Dis 2005; 19:30916. 11 Barker-Collo S, Feigin VL, Parag V, Lawes CM, Senior H. Auckland Stroke Outcomes Study. Part 2: cognition and functional outcomes 5 years poststroke. Neurology 2010; 75:160816. 12 Narasimhalu K, Ang S, De Silva DA et al. The prognostic effects of poststroke cognitive impairment no dementia and domain-specic cognitive impairments in nondisabled ischemic stroke patients. Stroke 2011; 42:8838. 13 Nys GM, van Zandvoort MJ, de Kort PL, Jansen BP, de Haan EH, Kappelle LJ. Cognitive disorders in acute stroke: prevalence and clinical determinants. Cerebrovasc Dis 2007; 23:40816. 14 Lesniak M, Bak T, Czepiel W, Seniow J, Czlonkowska A. Frequency and prognostic value of cognitive disorders in stroke patients. Dement Geriatr Cogn Disord 2008; 26:35663. 15 Ballard C, Stephens S, Kenny R, Kalaria R, Tovee M, OBrien J. Prole of neuropsychological decits in older stroke survivors without dementia. Dement Geriatr Cogn Disord 2003; 16:526. 16 Looi JC, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999; 53:6708. 17 Reed BR, Mungas DM, Kramer JH et al. Proles of neuropsychological impairment in autopsy-dened Alzheimers disease and cerebrovascular disease. Brain 2007; 130:7319. 18 Ingles JL, Wentzel C, Fisk JD, Rockwood K. Neuropsychological predictors of incident dementia in patients with vascular cognitive impairment, without dementia. Stroke 2002; 33:1999 2002. 19 Schneider JA, Boyle PA, Arvanitakis Z, Bienias JL, Bennett DA. Subcortical infarcts, Alzheimers disease pathology, and memory function in older persons. Ann Neurol 2007; 62:5966. 20 Jaillard A, Grand S, Le Bas JF, Hommel M. Predicting cognitive dysfunctioning in nondemented patients early after stroke. Cerebrovasc Dis 2010; 29:41523. 21 Hoffmann M. Higher cortical function decits after stroke: an analysis of 1,000 patients from a dedicated cognitive stroke registry. Neurorehabil Neural Repair 2001; 15:11327. 22 Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol 2009; 8:100618. 23 Srikanth VK, Quinn SJ, Donnan GA, Saling MM, Thrift AG. Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based rst-ever stroke cohort. Stroke 2006; 37:247983. 24 Nys GM, Van Zandvoort MJ, De Kort PL et al. Domain-specic cognitive recovery after rst-ever stroke: a follow-up study of 111 cases. J Int Neuropsychol Soc 2005; 11:795806. 25 Lazar RM, Minzer B, Antoniello D, Festa JR, Krakauer JW, Marshall RS. Improvement in aphasia scores after stroke is well predicted by initial severity. Stroke 2010; 41:14858. 26 Lazar RM, Antoniello D. Variability in recovery from aphasia. Curr Neurol Neurosci Rep 2008; 8:497502. 27 Hochstenbach JB, den Otter R, Mulder TW. Cognitive recovery after stroke: a 2-year follow-up. Arch Phys Med Rehabil 2003; 84: 1499504. 28 Desmond DW, Moroney JT, Sano M, Stern Y. Recovery of cognitive function after stroke. Stroke 1996; 27:1798803. 29 Gottesman RF, Hillis AE. Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke. Lancet Neurol 2010; 9:895905. 30 Hillis AE. Aphasia: progress in the last quarter of a century. Neurology 2007; 69:20013.
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Conclusion
General patterns can be detected in the prole 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-specic cognitive processes, and new research into how structural damage affects functional networks will further increase our understanding. Determining the causes of diffusely represented cognitive decits is difcult but may well be related to sub-clinical vascular changes and subtle abnormalities in white matter; such factors are starting to be revealed by new imaging techniques. Cognitive rehabilitation approaches have been relatively successful for focal cortical decits but less so for more generalized cognitive impairment. Repetitive transcranial magnetic stimulation and prism adaptation are two very different techniques to manipulate neural activity and drive plasticity. 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.

References
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