Topical review

Long-term neuropsychological and functional outcomes in

stroke survivors: current evidence and perspectives for
new research
Valery L. Feigin1, Suzanne Barker-Collo2, Harry McNaughton3, Paul Brown4, and
Ngaire Kerse5

good-quality population-based studies for evaluating the

Aims To appraise the literature on long-term neuropsycholo-
gical 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 prog-
nostic factors of long-terms stroke functional and neuropsy-
chological outcomes is of paramount importance for
evidence-based clinical decision making, including the ratio-
nale, planning, provision and allocation of health services,
and the development of effective interventions.
Summary of review Stroke has an enormous physical, emo-
tional and economic impact on the patients, families and
society. However, accurate data on frequency, relationship
and predictors of various long-term functional (body func-
tioning, 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
Correspondence: Associate Professor Valery L. Feigin, Clinical Trials
Research Unit, School of Population Health and Department of Medicine,
Faculty of Health & Medical Sciences, University of Auckland, PO Box
92019, Auckland, New Zealand. Tel: 164 9 3737599 ext. 84728;
Fax: 164 9 3731710; e-mail: v.feigin@ctru.auckland.ac.nz
1
Clinical Trials Research Unit, School of Population Health and Depart-
ment of Medicine, Faculty of Health & Medical Sciences, University of
Auckland, Auckland, New Zealand
2
Department of Psychology, Faculty of Science, University of Auckland,
Auckland, New Zealand
3
Medical Research Institute of New Zealand, University of Auckland,
Auckland, New Zealand
4
Health Systems Section, University of Auckland, Auckland, New Zealand
5
Department of General Practice, School of Population Health, University
of Auckland, Auckland, New Zealand
frequency and prognostic factors of long-term functional
and neuropsychological outcomes of stroke in various
populations.
Key words: stroke, neuropsychological outcomes, functional
outcomes, long-term outcomes
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 de-
clined steadily over the last few decades, stroke incidence
trends differ between countries and the overall number of
stroke survivors tends to increase (2).
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

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Journal compilation & 2008 International Journal of Stroke Vol 3, February 2008, 33–40 33
 Topical review
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, 7, 9) 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 popula-
tion-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, in-
tracerebral haemorrhage, subarachnoid haemorrhage (SAH),
outcome(s), neuropsychological, cognitive, impairment, dis-
ability, 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 classi-
fied into body functioning (any loss or abnormality of func-
tions, including neuropsychological functions), activities
(related to tasks and actions by an individual such as con-
sequences of impairment in terms of functional performance)
and participation (involvement in a life situation) and envir-
onment (disadvantage to the individual resulting from im-
pairment and disability, including handicap and quality of
34 Journal compilation & 2008 International Journal of Stroke Vol 3, February 2008, 33–40
V. L. Feigin et al.
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 neu-
ropsychological 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 psycho-
logical factors are important in determining functional out-
comes 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 impair-
ment in stroke survivors (4, 22, 42), and neither long-term
profiles of neuropsychological deficits nor their relationship
with other long-term functional outcomes have been estab-
lished. In addition, most studies that have looked at neurop-
sychological 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.
& 2008 The Authors.
 V. L. Feigin et al.
For example, a population-based study in South London (4)
compared cognitively impaired subjects [Mini-Mental State
Examination (MMSE) o24, n 5 248 (38%)] with cognitively
intact subjects (MMSE 24–30, n 5 397). Cognitive impairment
at 3 months after stroke was associated with older age [age Z75;
odds ratio (OR) 5 2
5, 95% confidence interval (CI) 5 1
5–4
2],
ethnicity [Caribbean/African (OR 5 1
9, 95% CI 5 1
2–3
2) and
Asian (OR 5 3
4, 95% CI 5 1
1–10
2)], lower socioeconomic
class (OR 5 2
1, 95% CI 5 1
3–3
3), left hemispheric lesion
(OR 5 1
6, 95% CI 5 1
01–2
4), visual field defect (OR 5 2
0,
95% CI 5 1
2–3
2) and urinary incontinence (OR 5 4
8, 95%
CI 5 3
1–7
3). At 4 years after stroke, cognitive impairment was
associated with death or disability (BIo15; OR 5 2
2, 95%
CI 5 1
1–4
5). However, in this study cognitive impairment
was assessed by means of the MMSE test only and no compre-
hensive 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 5 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 con-
ducted. 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 institutionalisa-
tion 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 (impair-
ment), activity (disability) and participation (handicap and
quality of life) has been documented (40, 49–54), these
relationships are not simple (49, 55, 56) 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
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Journal compilation & 2008 International Journal of Stroke Vol 3, February 2008, 33–40
Topical review
due to difficulties in socialising and maintaining connections
with friends and relatives. Many stroke survivors may experi-
ence 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 be-
tween 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 5 639) and compared with that in the age- and sex-matched
general population controls (n 5 310). 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 popula-
tion. 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 func-
tional 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 regis-
tered 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 (BIo15). The limitations of this
35
 Topical review
study include: a relatively short (1 year) follow-up period,
exclusion of patients with prestroke disability, no infor-
mation 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, 65, 66), 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 investi-
gated health outcomes by stroke subtype (4, 56, 73). 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 Commu-
nity Stroke Project classification of stroke subtypes was found
in the South London population-based study (4), no informa-
tion 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 5 216) 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
36 Journal compilation & 2008 International Journal of Stroke Vol 3, February 2008, 33–40
V. L. Feigin et al.
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 assess-
ment 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 func-
tional status 2 years poststroke.
In a population-based study in Perth, Australia (n 5 152),
factors that were associated with poor outcome (death or
disability) at 5 years included increasing age, baseline disabil-
ity, 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 King-
dom (4, 61), initial incontinence was found to be the best
predictor of moderate or severe disability (BIo15) at 1 year
after stroke; however, it remains unclear whether this associa-
tion 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, 103, 104), 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, 102, 105).
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).
& 2008 The Authors.
 V. L. Feigin et al.
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 (MRSZ3), 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 5 1
9,
95% CI 5 1
2–3
2) and Asian ethnicity (OR 5 3
4, 95%
CI 5 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 measure-
ment 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
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Journal compilation & 2008 International Journal of Stroke Vol 3, February 2008, 33–40
Topical review
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, plan-
ning, provision, and allocation of health services and the
development of effective interventions.
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