Long-Term Neuropsychological and Functional Outcomes in Stroke Survivors: Current Evidence and Perspectives for New Research

Abstract

Aims

To appraise the literature on long-term neuropsychological and functional outcomes in stroke survivors and identify the gaps, challenges and future research in this area. Background Stroke care resources are scarce, and the number of stroke survivors is likely to increase with the ageing of the population. Thus, evaluating the cost, frequency and prognostic factors of long-terms stroke functional and neuropsychological outcomes is of paramount importance for evidence-based clinical decision making, including the rationale, planning, provision and allocation of health services, and the development of effective interventions.

Summary of review

Stroke has an enormous physical, emotional and economic impact on the patients, families and society. However, accurate data on frequency, relationship and predictors of various long-term functional (body functioning, activity and participation) outcomes and costs of stroke are scarce, and no accurate and comprehensive data exist on long-term neuropsychological outcomes and their relationships with other functional outcomes poststroke.

Conclusions

There is a lack of accurate data on the frequency, relationship and predictors of various long-term functional outcomes and costs of stroke. There is a pressing need for good-quality population-based studies for evaluating the frequency and prognostic factors of long-term functional and neuropsychological outcomes of stroke in various populations.

Introduction

Stroke is the second most common cause of death worldwide and the most frequent cause of disability in adults in many countries, having an enormous physical, psychological and financial impact on the patients, families, the health care system and society. Moreover, stroke burden is projected to increase from around 38 million disability-adjusted life years (DALYs) lost globally in 1990 to 61 million DALYs*** in 2020 (1). Although stroke mortality in Western populations has declined steadily over the last few decades, stroke incidence trends differ between countries and the overall number of stroke survivors tends to increase (2).

Keywords

stroke neuropsychological outcomes functional outcomes long-term outcomes

Stroke often results in psychologic distress and limitations across multiple domains of functioning and some outcomes may have independent prognostic implications (3, 4). Thus, it is important to exercise a multifocal approach to studying stroke outcomes and include patient-centred measures that evaluate different functions (4). Only by this approach can the impact of stroke on the patient as a whole be understood and quantified. However, there is still no consensus on the best measures of stroke outcome, especially long-term outcome (5). Many commonly used measurements, such as the Barthel Index (BI), modified Rankin Scale (MRS) and Short Form 36 questionnaire (SF-36), assess only specific aspects of stroke outcome [e.g., BI, MRS assess physical functioning, including activities of daily living (ADL)] and have significant floor and/ or ceiling effects (6, 7). In addition, none of these measures assess hand function, which is known to be among the most frequently persisting consequences of stroke (8). Until recently, there was no reliable stroke-specific outcome measure that integrated measurements of impairment, disability, handicap and quality of life. Recently validated and developed for these purposes, the Stroke Impact Scale (5, 5, 7) has the potential to fill this gap, but it has not been tested in a population-based setting for long-term outcomes.

Most of the existing data on stroke outcomes and costs are restricted to cross-sectional studies with a short-term follow-up and selection bias due to inclusion of only participants referred to hospital and/or rehabilitation settings; have poor verification of stroke subtypes that leads to lumping together different stroke subtypes; have small sample sizes that are inadequate for testing of stated hypotheses; and suffer from a lack of standardisation of functional outcome measures that leads to inconsistency, incomprehensiveness and questionable reliability of their findings (10). In addition, there are no population-based studies of ethnic differences in long-term functional outcomes or costs of stroke. There are few population-based studies of stroke survival beyond 12 months (11 –18), and even fewer of other outcomes such as quality of life (10, 19), disability (20, 21), cognition and mood disorders (even including those with 12 months of follow-up) (4, 22 –27). There is also a lack of comprehensive studies of long-term neuropsychological outcomes in stroke survivors (3, 10). Furthermore, to date, there is no population-based study published on the relationships between various long-term neuropsychological impairments and functional outcomes (i.e., disability, handicap and quality of life) in survivors of stroke, nor on the frequency and prognostic factors of these outcomes by stroke subtype. In this narrative review, we aim to appraise the literature published on stroke outcomes, with an emphasis on the long-term functional and neuropsychological outcomes and population-based studies.

Methods

MEDLINE, PsycINFO, PubMed and EconLit database searches for the period from 1966 to May 2007 were conducted, with the key words: stroke, cerebral infarction, ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage (SAH), outcome(s), neuropsychological, cognitive, impairment, disability, handicap, quality of life, longitudinal, cross-sectional, population-based, survey, cost(s) and economic. Reference lists from relevant publications retrieved from the databases were hand-searched for other relevant publications. According to the recent International Classification of Functioning (ICF), Disability and Health (28), poststroke outcomes were classified into body functioning (any loss or abnormality of functions, including neuropsychological functions), activities (related to tasks and actions by an individual such as consequences of impairment in terms of functional performance) and participation (involvement in a life situation) and environment (disadvantage to the individual resulting from impairment and disability, including handicap and quality of life). The ICF was shown to be a useful tool to examine and compare the contents of instruments in stroke rehabilitation (29). The costs of illness (COI) studies were classified into incidence- and prevalence-based studies (30).

Results

Why study outcomes of stroke on a community level?

Population-based information on the long-term outcomes of stroke in terms of survival, impairment, disability, handicap and quality of life is important for several reasons: (1) it allows unbiased estimates of the long-term outcomes of stroke that can be useful to survivors, families, providers and healthcare systems to plan for the future; (2) it allows identification of predictive factors that can be used for continuing evidence-based rehabilitation and educational programmes for stroke patients and their families at various time points after stroke; (3) it serves as a baseline for the evaluation of preventive and/or therapeutic methods; and (4) it is crucial for accurate health-care planning and delivery of appropriate interventions at various community and institutional levels. This information can also provide important insights into the natural history (including trends in natural history), predictors of, and relationship between, various long-term outcomes in stroke survivors and form a basis for developing preventive/rehabilitation strategies to be tested in randomised clinical trials aimed at improving poststroke outcomes.

Importance of studying neuropsychological outcomes in stroke

Important, but often neglected outcomes of stroke are neuropsychological sequelae, which occur in nearly half the survivors (31). In one study of short-term (mean 72·2 days) neuropsychological functioning in 229 Dutch stroke patients, it was found that over 70% suffered impaired information processing and at least 40% suffered difficulties with memory, visuospatial and constructive skills, language and arithmetic (32). There is an accumulating body of evidence that psychological factors are important in determining functional outcomes after stroke (4, 23, 33 –41). While various aspects of neuropsychological deficits have been the focus of research in selected subgroups of stroke patients, there is a lack of population-based evidence on neuropsychological impairment in stroke survivors (4, 4, 22), and neither long-term profiles of neuropsychological deficits nor their relationship with other long-term functional outcomes have been established. In addition, most studies that have looked at neuropsychological impairment by stroke subtypes have not used a comprehensive neuropsychological battery of tests and have been confined to population sources from acute care and rehabilitation facilities.

For example, a population-based study in South London (4) compared cognitively impaired subjects [Mini-Mental State Examination (MMSE) <24, n = 248 (38%)] with cognitively intact subjects (MMSE 24–30, n = 397). Cognitive impairment at 3 months after stroke was associated with older age [age ≥ 75; odds ratio (OR) = 2·5, 95% confidence interval (CI) = 1·5·4·2], ethnicity [Caribbean/African (OR = 1·9, 95% CI = 1·2–3·2) and Asian (OR = 3·4, 95% CI = 1·1·10·2)], lower socioeconomic class (OR = 2·1, 95% CI = 1·3–3·3), left hemispheric lesion (OR = 1·6, 95% CI = 1·01–2·4), visual field defect (OR = 2·0, 95% CI = 1·2–3·2) and urinary incontinence (OR = 4·8, 95% CI = 3·1–7·3). At 4 years after stroke, cognitive impairment was associated with death or disability (BI<15; OR = 2·2, 95% CI = 1·1–4·5). However, in this study cognitive impairment was assessed by means of the MMSE test only and no comprehensive neuropsychological battery of tests was performed. In addition, MMSE assessment could not be performed on 23% of the patients, thus introducing a measurement bias.

Short-term (3 months) cognitive impairment was evaluated by a battery of neuropsychological tests in a small (n = 99) population-based case-control study in Melbourne, Australia (22). The study revealed that mild to moderate stroke severity was associated with a significant risk of cognitive impairment at 3 months after stroke [relative risk (RR), 1·5; 95% CI 1·1–2·1], attributable mainly to a greater risk of single-domain cognitive impairment (RR, 2·8; 95% CI 1·5–5·3) but not multiple-domain cognitive impairment (RR, 1·2; 95% CI 0·8–1·9). Unfortunately, no longer term assessment was conducted. Cerebrovascular risk factors were not shown to be independent risk factors for poststroke vascular dementia in some studies (43), and although stroke volume appears to be is a significant determinant of dementia (43) it does not predict mild cognitive impairment (44).

Despite the above, there is evidence that age and cognitive impairment are more important predictors of institutionalisation 3 years after a stroke than the severity of the physical disability (45), and that some aspects of neuropsychological functioning (e.g., presence of neglect, aphasia, anosognosia and verbal memory and attention deficits) are likely to be important predictors of other poststroke functional outcomes (41, 46). Standards for identifying patients with poststroke cognitive impairments have been developed only recently (47, 48).

Long-term body functioning, activity and participation in stroke survivors

Although a relationship between body functioning (impairment), activity (disability) and participation (handicap and quality of life) has been documented (40, 49 –54), these relationships are not simple (49, 49, 55) and further research on their interrelationships is warranted (52, 57). For example, people with prosopagnosia (inability to recognise well-known individuals visually) may have preserved physical functioning and have no disability, and yet experience significant handicap due to difficulties in socialising and maintaining connections with friends and relatives. Many stroke survivors may experience substantial functional recovery in the presence of major neurological deficits and, conversely, survivors who achieved independence in ADL may have residual deficits in higher levels of physical functioning (e.g., instrumental activities). Evidence is accumulating on the importance of mood and cognitive impairment on HRQoL in stroke survivors (58) and their family caregivers (59). Studying the relationships between various functional outcomes may help in the planning of rational and cost-effective interventions in the context of limited resources (56).

While the number of studies of functional outcomes (especially disability and neurological impairments) in stroke survivors is substantial (60), there have been few population-based studies of the long-term disability, handicap or quality of life in stroke survivors (4, 10, 19, 21, 61). Two early population-based stroke incidence studies in Auckland (1981–1982 and 1991–1992) showed that approximately 55% of 3-year stroke survivors have incomplete recovery, and one-third of them require assistance in at least one self-care activity (21). In the 1991–1992 study (10), health-related quality of life (HRQoL measured by the SF-36 questionnaire) and basic activities of daily living were assessed in stroke survivors 6 years after stroke (n = 639) and compared with that in the age- and sex-matched general population controls (n = 310). The authors found that although the majority of stroke survivors (77%) were living at home, 42% were dependent in at least one aspect of (basic care) activities of daily living and they had lower scores for the physical health, general health, vitality and social function components of HRQoL compared with the general population. However, these studies did not address other important functional outcomes or the associations between various outcomes, and did not look at outcomes by stroke subtypes (CT/MRI head scanning was not available at that time for the majority of the patients). No predictive modelling of functional outcome was undertaken in this report. In the Perth Community Stroke Study (Australia, 1989–1994) (20), 152 stroke patients (41% of acute stroke patients) survived to 5 years. Of survivors who were neither institutionalised nor disabled at the time of their initial stroke, 21 (14%) were institutionalised in a nursing home and 47 (36%) were disabled at 5 years after stroke. However, no information was available on quality of life and the study was not powered to look at stroke subtypes. In the North East Melbourne Stroke Incidence Study, increasing age, lower socioeconomic status and markers of stroke severity were found to be independent baseline predictors of low HRQoL at 5 years after stroke (19). In a larger and more recent population-based study in South London (United Kingdom 1995–2000) (4, 61), of 639 registered stroke patients, 392 without previous disability survived and were assessed for disability at 3 months, of whom 34 (9%) were severely disabled and 60 (15%) were moderately disabled. Of 225 survivors (35%), at 12 months after stroke, 11% had moderate or severe disability (BI < 15). The limitations of this study include: a relatively short (1 year) follow-up period, exclusion of patients with prestroke disability, no information on HRQoL and other important outcomes and no information on functional outcomes by pathological subtypes of stroke.

Do functional outcomes differ in different stroke subtypes?

Stroke is a heterogeneous disorder that consists of three major pathological types, each of which has differing aetiologies (62 –64), incidence rates (2, 2, 65), managements and short- to medium-term outcomes (66 –72). If specific stroke subtypes are shown to have differing functional outcomes, then the needs for community and rehabilitation services, educational and interventional programmes in stroke patients and their families could also be different (56). However, data on long-term outcomes in survivors of different stroke subtypes are scarce, limited to a 1-year follow-up and often inconsistent.

We found only three population-based studies that investigated health outcomes by stroke subtype (4, 4, 56). In the study in Melbourne (Australia) (56), handicap (measured by the London Handicap Scale) differed significantly with the severity of disability (measured by the BI) in ischaemic stroke subtypes (defined by the Oxfordshire stroke classification) at 12 months. However, no information on haemorrhagic stroke subtypes was provided in the publication. In an Australasian study (73), incomplete recovery at 1 year after SAH was found in 46% of the survivors, of which ongoing memory problems were recorded in 50%, mood abnormalities in 39% and speech problems in 14%, while a substantial proportion of survivors had a diminished level of HRQoL. Although no association between cognitive impairment and the Oxfordshire Community Stroke Project classification of stroke subtypes was found in the South London population-based study (4), no information on pathological subtypes of stroke was provided and the authors did not analyse other important functional outcomes. In a hospital-based study of 3-month survivors of different stroke subtypes followed up for 20 months (74), Woo et al. found that stroke subtype and size, position and the territory of the lesion on brain CT did not influence long-term outcomes and that factors affecting long-term survival and disability are different from those affecting outcome immediately after stroke. However, the sample size was relatively small (n = 216) and the study was not population-based, thus being subjected to selection bias and type I error, especially for haemorrhagic stroke subtypes.

Predictors of stroke outcomes

Studying predictors of long-term outcomes in stroke survivors would allow identification of patients who may benefit from specific rehabilitation services, may improve planning of stroke care and rehabilitation services and would facilitate better information provision to patients and their families with regard to the patient's potential for recovery and the likelihood of surviving in the long term. Ideally, predictive models of stroke outcomes should be based on population-based studies in which various potential predictors of stroke outcomes are described adequately; the standard diagnostic criteria and validated standardised measures of outcomes are used (75). Although prognostic factors of stroke outcomes have been the subject of considerable discussion in the literature (38, 66, 76 –88), there have been only a few studies that have addressed some aspects of this issue in the population-based setting (4, 20, 61, 73).

The literature linking neuropsychological functioning to outcome after a neurological event has to date focused on prediction of specific outcomes in small samples and assessment of only specific areas of neuropsychological functioning, such as memory, attention, language, visuospatial or executive functions. For example, Goldstein et al. (89) found that assessments of memory significantly predict instrumental daily living skills in the elderly. Similarly, Robertson et al. (90) reported that sustained attention is predictive of functional status 2 years poststroke.

In a population-based study in Perth, Australia (n = 152), factors that were associated with poor outcome (death or disability) at 5 years included increasing age, baseline disability, hemiparesis and recurrent stroke (20). No predictors of complete recovery (as determined by the SF-36. How can you determine complete recovery using the SF-36?) from SAH were determined in a population-based study of SAH in Australasia (73), but the follow-up period was restricted to 1 year and no other measures of disability and handicap were undertaken in this report. In a population-based study in the United Kingdom (4, 61), initial incontinence was found to be the best predictor of moderate or severe disability (BI< 15) at 1 year after stroke; however, it remains unclear whether this association holds true in the long term. Moreover, there is no information from a population-based study on other factors (e.g., mood disorders, socioeconomic status, family support, etc.) that may influence a long-term poor or good outcome after stroke. There is evidence that reduction of disability after stroke is a more informative predictor of long-term survival than the initial disability status (91).

Previous mortality (92 –94) and population-based studies (95 –102) have consistently shown greater incidence, case fatality and mortality rates of stroke in non-Caucasian groups compared with Caucasians, but there have been very few studies of ethnic differences in the long-term and functional outcomes of stroke (4, 4, 103), and only one of them was population-based (4). The issue of ethnic differences in stroke outcomes is of particular importance for multiethnic societies, in which the risk of stroke and poor survival in non-White people is substantially higher than that in Caucasians and tends to increase over time (99, 99, 102).

Data from the recent surveys showed that African-American stroke survivors in the United States had greater activity limitations than Caucasian stroke survivors (105, 106).

In a small hospital-based study of 181 survivors in Wellington (103), non-Caucasian survivors at 12 months posthospital discharge were more likely to be dependent (MRS ≥ 3), had significantly lower Functional Independence Measure scores, lower London Handicap Scores and lower scores on the SF-36 domains of physical functioning and vitality and Physical Component Summary score. Poorer functional outcomes in African Americans compared with Caucasians were also found in the United States, but, like the aforementioned study by McNaughton et al. (103), this study was not population-based. The only population-based study of ethnic differences in stroke outcomes published to date was carried out in South London (4). In this study, cognitive impairment at 3 months after stroke was associated with Caribbean/African (OR= 1·9, 95% CI = 1·2–3·2) and Asian ethnicity (OR = 3·4, 95% CI= 1·1–10·2), but these associations were not statistically significant at 4 years after stroke. However, assessment of cognitive function was limited to the MMSE score measurement and the study did not analyse ethnic differences in other important functional outcomes, including disability, handicap and health-related quality of life.

The importance of estimating the lifetime costs of stroke

Stroke represents a significant financial drain on healthcare resources and places a burden on families and caregivers (107). Recent reviews of COI studies have summarised the evidence on the direct and indirect costs of stroke to society during the initial years after a stroke (108, 109). Estimates of long-term (lifetime) costs range from US$18 538 to US$74 294 per patient (108). However, there is considerable variability across studies in the methodology used to calculate the cost of stroke, including a failure to include all relevant cost categories, differentiate the cost of co-morbidities and include the costs to caregivers (110). In addition, the cost estimates vary considerably across countries, highlighting that the costs of stroke are highly dependent on the structure of the health system.

There are two types of economic COI studies of stroke: prevalence-based studies, which identify the total cost in a given time period (e.g., year) for all those suffering from the ill effects from stroke (regardless of when the stroke occurred), and incidence-based studies, which estimate the lifetime costs of stroke only for those people who have a stroke in the period of observation (e.g., year). Whereas prevalence studies are concerned with identifying the current burden on society for all those suffering ill effects from stroke, incidence studies attempt to understand the future or lifetime costs associated with the condition.

Incidence studies require accurate estimates of the survival poststroke and the resources required at various stages of the condition. Because of the difficulty in tracking lifetime costs associated with stroke, previous studies have assessed resources use over a finite period (e.g., 1 year), and then used economic modelling to estimate the long-term, lifetime costs of stroke (15–30 years poststroke). As described in recent reviews of COI studies (108 –110), no study has tracked both direct and indirect costs beyond 2 years poststroke. This short follow-up period means that little is known of the long-term costs of stroke.

Conclusions

As a leading cause of disability in adults, stroke has an enormous physical, emotional and economic impact on the patients, families and society. However, there is lack of accurate data on frequency, relationship and predictors of the various long-term functional outcomes and costs of stroke. Given the scarce resources available for stroke care and the likely increase in stroke survivors due to the ageing of the population, evaluating the true frequency and prognostic factors of long-term functional and neuropsychological outcomes of stroke in various populations is of paramount importance for evidence-based clinical decision making, including the rationale, planning, provision, and allocation of health services and the development of effective interventions.

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