Poststroke dementia - The Lancet

Review

Poststroke dementia Didier Leys, Hilde Hénon, Marie-Anne Mackowiak-Cordoliani, Florence Pasquier Lancet Neurol 2005; 4: 752–59 Stroke department (D Leys MD,H Hénon MD), and Memory Centre (M-A Mackowiak-Cordoliani MD, F Pasquier MD), Department of Neurology, University of Lille II, EA 2691, Rue Emile Laine, Lille, France Correspondence to: Prof Didier Leys [email protected]

Dementia is one of the major causes of dependency after stroke. The prevalence of poststroke dementia (PSD)— defined as any dementia occurring after stroke—is likely to increase in the future. In community-based studies, the prevalence of PSD in stroke survivors is about 30% and the incidence of new onset dementia after stroke increases from 7% after 1 year 48% after 25 years. Having a stroke doubles the risk of dementia. Patient-related variables associated with an increased risk of PSD are increasing age, low education level, dependency before stroke, prestroke cognitive decline without dementia, diabetes mellitus, atrial fibrillation, myocardial infarction, epileptic seizures, sepsis, cardiac arrhythmias, congestive heart failure, silent cerebral infarcts, global and medial-temporal-lobe atrophy, and white-matter changes. Stroke-related variables associated with an increased risk of PSD are stroke severity, cause, location, and recurrence. PSD might be the result of vascular lesions, Alzheimer pathology, white-matter changes, or combinations of these. The cause of PSD differs among studies in relation to the mean age of patients, ethnicity, criteria used, and time after stroke. In developed countries, the proportion of patients with presumed Alzheimer’s disease among those with PSD is between 19% and 61%. Patients with PSD have high mortality rates and are likely to be functionally impaired. These patients should be treated according to the current guidelines for stroke prevention.

Introduction In developed countries, stroke is the major cause of physical disability in adults, the second most common cause of dementia, and the third leading cause of death (after coronary-artery diseases and cancers).1 In a population of 1 million inhabitants, 2400 patients will have a stroke every year, of whom fewer than 50% will be independent 1 year later.2 Many independent survivors have residual physical or cognitive deficits, or behavioural changes which can affect family life and have professional consequences.3 Poststroke dementia (PSD) is one of the main causes of dependency in survivors and includes any dementia after a stroke, irrespective of its cause—ie, vascular, degenerative, or mixed. A huge increase in prevalence and burden of PSD is likely to happen4 because of the decline in mortality after stroke5 and ageing of populations.

Classification PSD includes all types of dementias that happen after stroke, irrespective of their cause. This concept is useful for patients who are followed up after stroke before their dementia can be diagnosed as either vascular dementia (VaD), degenerative dementia (especially Alzheimer’s disease), or mixed dementia (dementia as a result of the coexistence of vascular lesions of the brain and neurodegenerative lesions). VaD is a direct consequence of cerebral infarcts, haemorrhages, and white-matter changes.6 But not all patients who have had a stroke, have VaD. It might also be useful to focus on “cognitive impairment” rather than “dementia”, because cognitive impairment includes all cognitive consequences of stroke, even if they are not severe enough to meet criteria for dementia. In this review, vascular cognitive impairment will not be addressed. However, we should bear in mind that true cognitive burden of stroke is 752

underestimated because cognitive impairment without dementia is three times more common in people who have had a stroke than in those who have not.7

Descriptive epidemiology Prevalence In prevalence studies, PSD included both pre-existing dementia and new-onset dementia after stroke.8–23 In community-based studies with adjustment for age, the prevalence of dementia in people with a history of stroke is about 30%—ie, 3·5–5·8-times higher than in those who have not had stroke.24,25 In hospital-based studies, the prevalence of PSD (table 1) ranges from 5·9 to 32%.8–23 Attrition of patients as a result of mortality could explain why the prevalence of dementia was higher within 3 months after stroke than it was 1 year or more later (table 1): dementia is associated with a high mortality rate in stroke patients.26–33 Differences in prevalence among studies8–23 are explained by differences in the mean age of the study population, delay between stroke and cognitive assessment,34 and criteria for dementia.35 Erkinjuntti and colleagues35 studied the prevalence of dementia estimated with six commonly used classification systems in 1879 patients, age 65 years or older; the proportion of subjects with dementia varied from 3·1% with the International Classification of Diseases 10th revision (ICD-10)36 criteria, to 29·1% with the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) criteria.37 The six classification systems identified different groups of subjects as having dementia. The prevalence of dementia estimated with these criteria differs by a factor of ten, which has serious implications for research and treatments.35 With the DSM-III criteria and an extensive and detailed neuropsychological examination,8 the prevalence of PSD was 31·8%. With the more specific, but less sensitive34 ICD-10 criteria,36 http://neurology.thelancet.com Vol 4 November 2005

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the proportion of patients with dementia 1 year after stroke was 17·7%,9 compared with 26·3% reported after 3 months38 when dementia was diagnosed only on the basis of clinical judgment. Differences in inclusion criteria might also explain differences in the prevalence of PSD between studies. Patients with aphasia and those unable to undergo neuropsychological tests because of severe physical impairment—ie, those patients who are most likely to have severe cognitive impairments—were excluded from many studies, leading to a probable underestimation of the prevalence of dementia.10,39

Incidence Incidence studies are hampered by some of the same methodological issues as those in prevalence studies. Moreover, the incidence of PSD depends on whether pre-existing dementia was included or not in PSD: many cases of PSD are not actually new-onset dementia, but pre-existing dementia revealed after stroke; preexisting dementia is present in 7–16% of stroke patients,11,40–45 and undiagnosed before stroke in many patients.40 Crude incidences of PSD in different studies are reported in the figure. In a community-based study done over 25 years, the cumulative incidence of PSD was 7% after 1 year, 10% after 3 years, 15% after 5 years, 23% after 10 years, and 48% after 25 years.46 In hospitalbased studies, the incidence of PSD ranged from 9%47 to 16·8% after 1 year, 24% to 28·5%17 after 3 years, 21·5%48 to 33·3%38 after 4 years, and was 32%38,49 after 5 years. The risk of new-onset dementia was, however, much lower in the Lille Stroke Dementia cohort, in which only 6% of survivors who did not have dementia 6 months after stroke developed dementia during the following 30 months.17 In the Rochester study, the relative risk of dementia (the risk of dementia in stroke survivors divided by the risk of dementia in stroke-free controls) was 8·8 after 1 year (95% CI 6·8–10·9), 4·2 after 3 years (3·4–5·0), 3·5 after 5 years (2·9–4·1), 2·5 after 10 years (2·2–3·0), and 2·0 after 25 years (1·6–2·4).46 After exclusion of patients who had dementia for 1 year prior to stroke, the risk of dementia doubled in the stroke cohort during the whole follow-up.46 The risk of Alzheimer’s disease was also doubled after 25 years.46 Similar results were found in the Framingham study, 10 years after stroke, after adjustment for age, gender, education, and exposure to individual stroke risk factors (hazard ratio 2·4, 95% CI 1·6–3·7; absolute difference 8·2%).50 The only study where stroke was not associated with a higher risk of dementia was done in non-aphasic patients, with mild first-ever strokes, and only 1 year of follow-up.51 The selection of patients with mild deficits, and a short follow-up could explain the lack of associations between stroke and dementia in this study.51 Hospital-based studies provide similar findings; the risk of new onset dementia within 4 years after ischaemic stroke was five http://neurology.thelancet.com Vol 4 November 2005

Ref

Delay (months)*

Number of patients

Population characteristics

Dementia criteria

Prevalence (%)

12

7–10 days

726

Clinician’s opinion

16·3

14

1

220

3

337

Mattis dementia rating scale DSM III

32·0

8

31·8

10 11

3 3

110 280

NINDS-AIREN DSM IV

13·6 15·5

13

3

251

DSM III R

26·3

15

3

251

DSM IV

22·1

16

3

453

DSM III R

26·3

18

3

237

19

3

283

20

3

75

21

3

434

14

6

220

17

6

202

22, 23

6

146

9

12

339

Ischaemic stroke Age 60 years First-ever stroke Age 60–80 years Ischaemic stroke Age 55–85 years First-ever ischaemic stroke Stroke Age 60 years Ischaemic stroke Age 60 years Stroke Age 18 years Ischaemic stroke Age 60 years Stroke patients with no previous functional deficit Ischaemic stroke, no patient with previous TIA Ischaemic stroke associated with small vessel disease Ischaemic stroke Age 55 years First-ever stroke Age 60–80 years Stroke Age 40 years First-ever ischaemic stroke Age 40 years MMS 15 (acute stage) Stroke

17

12

202

22, 23

12

196

7

18

149

17

24

202

17

36

202

Stroke Age 40 years First-ever ischaemic stroke Age 40 years MMSE 15 (acute stage) Stroke Age 70 years Stroke Age 40 years Stroke Age 40 years

NINDS-AIREN

5·9

ICD-10

9·2

Clinical dementia rating scale 1 DSM IV Mattis Dementia Rating Scale ICD-10 DSM IV

13·3 27·2 26·0 22·8 8·5

Proxy-informant interview 16·8 based on ICD-10 ICD-10 21·4 DSM IV

10·0

DSM III R

28·0

ICD-10

21·6

ICD-10

19·2

Studies are classified by increasing delay after stroke onset. A single study might appear several times in this table if several assessments were performed at different time intervals after stroke onset. The relative risk compared with controls was 9. Delay means delay after stroke onset. The final diagnosis was based on criteria for dementia, without neuropathological study for most patients. *Months unless specified; MMSE=mini-mental state examination.

Table 1: Prevalence of poststroke dementia

times higher than in controls (crude incidence rate of dementia: 8·5 cases per 100 person-years in stroke patients, 1·4 cases per 100 person-years in controls).38 A combined analysis of patients from a previous cohort,38 and patients recruited later found a six times increased risk of dementia in patients with ischaemic stroke.52 Finally, hospital-based studies and community-based studies provide similar findings; stroke doubles the risk of dementia, this risk is the highest within the first 6–12 months after stroke (as almost one patient in five has dementia), and the risk of delayed dementia (including Alzheimer’s disease) is also doubled after stroke. 753

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50 Hospital based study

Kokmen et al, 199646

Community-based study

Incidence of dementia (%)

40 Tatemichi et al, 199438 30

Bornstein et al, 199649 Tatemichi et al, 199438

Henon et al, 200117 20

10


Altieri et al, 200448

Inzitari et al, 19989


Ballard et al, 200347 Kokmen et al, 199646

Neuroimaging characteristics

Kokmen et al, 199646 0 12

24

36

48

60

120

300

Delay after stroke (months)

Figure: Incidence of poststroke dementia at different time intervals after stroke onset, in hospital-based studies (red) and community-based studies (blue) When the reference appears several times, data provided correspond to different assessments at different time intervals in the same cohort of patients.

Determinants of poststroke dementia Patients’ demographics and clinical characteristics Increasing age is a major determinant of PSD.8–10,12–18,21,23,25,38,46,48,52–54 In the New York study, after a median follow-up of 21 months, 15% of patients with stroke age 60–69 years had new-onset dementia, 26% between 70–79 years, and 36% after age 80 years after adjustment for age; the risk of PSD did not depend on gender in most studies.8–13,15–17,21,24,38,48,52,53 A low education level was an independent predictor of PSD in most studies;8,11,18,21,23,54 when it was not an independent predictor10,15,17,19 the absence of a statistical link might be the result of poor statistical power, or a lack of patients with a high level of education in the study. The risk of PSD is higher in patients who were dependent before stroke.9–12,14,15 Prestroke cognitive decline (no dementia), assessed by standardised questionnaires, is also associated with a higher risk of PSD after 3 months8,20,55 and 3 years.16,17 Arterial hypertension—a risk factor for VaD and Alzheimer’s disease56—has not been clearly identified as a risk factor for PSD. However, there is an indirect argument suggesting that the higher the blood pressure, the greater the risk of dementia after stroke; in the perindopril protection against recurrent stroke study (PROGRESS), lowering of blood pressure in patients with prior stroke or TIA, independently on the baseline level of blood pressure, reduced the risk of dementia in patients with recurrences.57 In several other studies diabetes mellitus,10,16,17,53,58 atrial fibrillation,8–11,15,21,48,54 and myocardial infarction,59 were also independent risk factors for PSD. Hypoxic–ischaemic disorders, such as epileptic seizures, sepsis, cardiac arrhythmias and congestive 754

heart failure are independently associated with an increased risk of PSD.52,54,60 However, a statistical link between hypoxic–ischaemic disorders and dementia does not mean a causal association. The hypothesis that dementia increases the risk of hypoxic–ischaemic events is also a plausible one. The influence of hyperlipidaemia, hyperhomocysteinaemia, alcohol consumption, and cigarette smoking on PSD remains unproven.8,9,15–19,48,52,53 However, results about smoking should be interpreted with caution, because smoking influences both mortality and stroke recurrence.

To our knowledge, there is no study with functional neuroimaging techniques such as single-photonemission CT, PET, functional MRI, or spectroscopy, to identify predictors of PSD in large series of consecutive patients with stroke. Functional neuroimaging studies have provided a useful conceptual framework for the understanding of VaD, but have not addressed PSD. Silent infarcts are cerebral infarcts seen on CT or MRI scans that have never been associated with a corresponding neurological deficit. One study found no relation between silent infarcts and PSD,49 but the assessment of the pre-existing cognitive status was not standardised, and the study was underpowered. Other studies clearly identified silent infarcts as independent predictors of PSD.12,16,17,54 The influence of silent infarcts is more important when the delay between stroke and cognitive assessment is longer. In the Lille study, silent infarcts were associated with PSD in the third year but not in the second year,61 and in the Maastricht study silent infarcts were independently related with dementia after 1 year, but not after 1 month or 6 months.23 Global cerebral atrophy is associated with a higher risk of PSD.7,16,45,48,50,53 Medial-temporal-lobe atrophy is most common in patients with stroke who have preexisting dementia,62 but it can also be present in patients with stroke with no dementia. In the Lille study the cumulative proportion of 3-year survivors free of dementia was significantly lower in patients with medial-temporal-lobe atrophy (57·6% vs 80·8%).63 Medial-temporal-lobe atrophy clearly differentiates patients with dementia from those who do not have dementia after a first-ever ischaemic stroke, even after exclusion of patients who had prestroke cognitive impairment.54,64 Patients with stroke with medialtemporal-lobe atrophy might have preclinical Alzheimer’s disease, which is clinically revealed by stroke.65 However, medial-temporal-lobe atrophy is not specific to Alzheimer’s disease, as it has also been observed in VaD.66–68 In elderly patients with stroke and no dementia (with moderate to severe medial-temporallobe atrophy)—after adjusting for age, volume of infarcts and cortical atrophy—do notably worse in tests http://neurology.thelancet.com Vol 4 November 2005

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of learning, story recall, visual reproduction, block design, and mental speed,69 suggesting that, in elderly patients who have stroke but no dementia, medialtemporal-lobe atrophy is associated with poor memory and visuospatial functions, whereas verbal and executive functions are preserved. 69 Presence and severity of white-matter changes are independent predictors of PSD.11 However, there are major potential confounding factors: cerebral atrophy, which is more frequent in patients with white-matter changes; lacunar infarcts, which share a common pathogenesis with white-matter changes; and stroke recurrence, which is more common in patients with stroke and white-matter changes than those with stroke alone.12,65 In a study to determine the neuroimaging correlates of cognitive ability in patients with lacunar infarcts, leftfrontal-lobe atrophy and presence of thalamic infarct were independent predictors of worse cognitive performances.70 Finally, silent infarcts, global cerebral atrophy, medial-temporal-lobe atrophy, and whitematter changes are predictors of PSD.

Stroke characteristics Most studies found that a more severe clinical deficit at onset is associated with a higher risk of PSD.12,16,17,34 However, in studies that did not find this association,46,48,52 high mortality rates in patients with severe deficits may have created recruitment bias (because of a small delay between stroke onset and recruitment). The risk of PSD and its severity are not influenced by the type of stroke (ischaemic or haemorrhagic).7,8,15,17,18,23 However, differences in survival rates between stroke subtypes lead to difficulties in the interpretation of the results. In the Framingham study large-artery infarcts, lacunar infarcts, and infarcts of unknown origin were associated with a higher risk of PSD than cardioembolic infarcts.50 In other studies, the risk of PSD was lower in patients with small-vessel occlusion than in patients with large-arterial stroke.12,16,20,23 It is difficult to interpret these results because mortality rates are higher in types of infarcts leading to more severe deficits—ie, in patients who are most likely to develop PSD.10,16,20,52 Previous stroke, and stroke recurrence, are associated with a higher risk of PSD.8,9,12,19–21,46,53 Supratentorial lesions,15 left hemispheric 13,21,39,53,71,72 lesions, anterior and posterior cerebral artery territory infarcts,7,15,25 multiple infarcts,8,12 and “strategic infarcts”,73–76 were associated with PSD in at least two studies. Strategic infarcts are cerebral infarcts that can lead to dementia independent of any other factor—for example, in the absence of any other lesion. However, strategic locations (left angular gyrus, inferomesial temporal and mesial frontal locations, thalami, left capsular genu, and caudate nuclei) were described more than 20 years ago as single cases or in http://neurology.thelancet.com Vol 4 November 2005

Panel: Determinants of poststroke dementia Patients’ demographic and clinical characteristics Increasing age8–10,12–18,21,23,25,38,46,48,52,53 Low education level8,9,11,18,21,23,53 Prestroke dependency 8–12,14,15 Prestroke cognitive decline–no dementia8,16,17,20,45 High blood pressure57 Diabetes mellitus10,16,17,53,58 Atrial fibrillation, 8,9,11,15,21,48,54 Myocardial infarction,59 Epileptic seizures52,54 Sepsis52,54 Cardiac arrhythmias52,54 Congestive heart failure52,54 Patients’ neuroimaging characteristics. Silent infarcts12,13,16,17,23,54 Global cerebral atrophy11,16,48,50,53,79 Medial-temporal-lobe atrophy54,62–64 White-matter changes11,12 Stroke characteristics More severe clinical deficit at stroke onset12,16,17,34 Stroke recurrence8,9,12,16,19–21,46,53 Supratentorial lesions15,16 Left hemispheric lesions13,16,21,39,53,71,72 Anterior and posterior cerebral artery territory infarcts15,25,79 Strategic infarcts73–76 Multiple lesions8,10,12,48 This table includes determinants of poststroke dementia that have been found in at least two independent studies. A few determinants might not have been confirmed in other studies.

small series,73–76 without MRI, and without follow-up. Other vascular brain lesions interfering with the neuropsychological deficit cannot be excluded in the absence of MRI,77,78 and coexisting Alzheimer’s disease cannot be excluded in the absence of follow-up.65 The concept of strategic stroke should, therefore, be revisited with large prospective studies, MRI scans to exclude associated lesions, and a follow-up long enough to exclude associated Alzheimer’s disesase. Determinants of poststroke dementia that have been found in at least two independent studies are listed in the panel.79

Causes of poststroke dementia The most common causes of PSD are VaD, Alzheimer’s disease, and mixed dementia.8,12,13,15–17,46,50,80 Alzheimer’s disease, mixed Alzheimer’s disease and VaD account for 19–61% of patients with PSD (table 2). Only two studies, both done in Asia,11,19 did not find such a high proportion of Alzheimer’s disease in PSD. However, in one of these studies,19 the study population was 10 years younger than those recruited in other studies, and patients who were lost to follow-up at the 3 month assessment were more cognitively impaired at the acute 755

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Ref

Delay after stroke*

Number of patients†

Type of study

VaD (%)

AD (%)

ADVaD (%)

12 8 11 14 15 16 46 17 80 50

7–10 days 3 3 3 3 3 12 36 36 120

726 337 280 251 251 453 ·· 202 ·· ··

Hospital Hospital Hospital Hospital Hospital Hospital Community Hospital Community Community

39 81 98 56 75 57 ·· 67 100 51

36 19 ·· 36 25 39 41 33 ·· ··

25 ·· 2 ·· ·· ·· ·· ·· ·· 37

Studies are classified by increasing delay between stroke onset and neuropsychological assessment. A single study might appear several times in this table if several assessments were performed at different time intervals after stroke onset. *In months unless specified. †Provided only for hospital-based studies.

Table 2: Causes of new-onset poststroke dementia

stage. In the other study,11 the diagnosis of VaD was based on the DSM IV criteria for VaD, which are the less specific criteria.6,81–83 Vascular lesions have a prominent role in the development of PSD in the following circumstances: patients with stroke who are too young to have Alzheimer’s disease, and who have dementia just after stroke; when cognitive functions were normal before stroke, impaired immediately after, and did not worsen or improve over time; when a specific vascular condition known to cause stroke and dementia (eg, cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is proven by a specific marker; and when the lesion is located in a strategic area.73–76 Even when vascular lesions, Alzheimer’s pathology and white-matter changes do not lead to dementia by themselves, their cumulative effect can reach the threshold of lesions required to produce dementia;65 when stroke, white-matter changes, or both, occur in a patient with asymptomatic Alzheimer’s pathology, the period of preclinical Alzheimer’s disease might be shortened.65 This hypothesis is supported by the results of the following studies. In the Optima and in the Nun studies, among patients who met neuropathological criteria for Alzheimer’s disease, those with brain infarcts had poorer cognitive functions and a higher prevalence of dementia.84,85 In the dementia substudy of the Systolic Hypertension in Europe trial (SYST-EUR), nitrendipine decreased the incidence rate of stroke and Alzheimer’s disease,86 suggesting that stroke prevention reduces the risk of new-onset Alzheimer’s disease; previous cognitive decline and no dementia, likely to be degenerative in origin in most patients,87 is a risk factor for PSD.17 Most patients with previous cognitive decline and no dementia who developed PSD have a clinical presentation of Alzheimer’s disease, but it occurs months after a stroke. The concept of mixed dementia might be useful for these patients because it emphasises that these patients should be treated for 756

Alzheimer’s disease but should also receive an appropriate therapy to prevent stroke. Treatment of these patients as though they have Alzheimer’s disease, even if the time-course suggests Alzheimer’s disease, may make practitioners ignore the vascular component that is treatable, especially if the stroke occurred years before.

Influence of poststroke dementia on stroke outcome Mortality Both population-based studies26,27,29,38 and hospitalbased28 studies have shown that patients with PSD have higher mortality rates than patients without dementia, independent of age and comorbidities.26 The long-term mortality rate is two to six times higher in patients with PSD, after adjustment for demographic factors, associated cardiac diseases, stroke severity, and stroke recurrence.30–32,38 In patients with pre-existing dementia, mortality rates are two to five times higher.31,32 The increased mortality among patients with PSD might be the result of several factors. (1) Patients with dementia of any cause have high mortality.33 (2) Stroke mortality may be high in patients with dementia.33 (3) Dementia is associated with more severe vascular diseases and a higher risk of complications.38 (4) Dementia may worsen co-occurring disorders; patients with dementia may receive less aggressive stroke prevention,88,89 and less appropriate treatments of associated disorders90—although causes of death can be similar in patients with and without PSD and management was similar for both groups in the Lille study.31,32 (5) Patients with PSD may be less compliant to treatments necessary for stroke prevention (ie, antithrombotic agents and treatment of vascular risk factors), which could lead to less effective prevention of new vascular events and a higher mortality rate.

Stroke recurrence In the New York study,91 dementia diagnosed 3 months after stroke was associated with a three times greater increased risk of stroke recurrence (relative risk: 2·71; 95% CI 1·36–5·42). Dementia might be a surrogate marker for a more severe vascular disease leading to an increased risk of recurrence, and less intensive stroke prevention and lack of compliance that can contribute to the increased risk of recurrence.91 White-matter changes could also be a confounding factor because they are associated with an increased risk of stroke recurrence.17

Functional outcome The few available data on functional outcome suggest more impaired and more activities than patients with PSD.12,13,15,19,24

the influence of PSD on that patients with PSD are dependent in daily living stroke who do not develop

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Treatment of PSD PSD is not a specific entity requiring a specifc treatment. Patients with PSD are patients with dementia and also patients with stroke. Current guidelines for stroke prevention should be applied, but we should bear in mind that the specific issue of secondary prevention of stroke in patients with dementia (either pre-existing or new-onset dementia) is not addressed in any guidelines. However, lowering of blood pressure could, in theory, reduce the incidence of cognitive decline because of a reduction in recurrence rates and indirect effects on the anticipation of the clinical onset of Alzheimer’s disease:65 several controlled trials showed a beneficial effect of lowering blood pressure on the risk of dementia.57,86,92 A symptomatic approach to the dementia syndrome is necessary, depending on the presumed cause (Alzheimer’s disease, VaD, or mixed). There have been no trials specifically done in PSD. However, both Alzheimer’s disease and VaD share a cholinergic deficit,93,94 and both disorders show improvement when treated with cholinesterase inhibitors.95–100 Patients with Alzheimer’s disease with vascular risk factors receive greater symptomatic benefits than patients with pure Alzheimer’s disease after short-term treatment with rivastigmine—an inhibitor of acetylcholinesterase and butyrylcholinesterase.101 The additional apparent benefits on disease progression detected in patients with hypertension and Alzheimer’s disease might be linked to drug effects on cerebrovascular factors. These findings could have an important effect on the way cholinesterase inhibitors are prescribed.101

Perspectives. PSD is a dementia syndrome occurring after stroke irrespective of its cause—eg, VaD, degenerative dementia, or both. The prevalence of PSD is likely to increase in the future because of better survival after stroke and ageing of the population. Recognition of patients with PSD is important because they have higher Search strategy and selection criteria References for this review were identified by searches of MEDLINE between 1970 and April 30, 2005, and references cited by relevant articles. Articles were selected on the basis of the presence of the following key words: “dementia”, “cognitive impairment”, “stroke”, “cerebral infarct”, or “cerebral ischemia” (or ischaemia), or “cerebral hemorrhage” (or haemorrhage). Abstracts and reports from meetings were not included. Papers published in languages other than English, French, and German were not reviewed. The final reference list was generated based on originality and relevance to the topics covered in the review. We selected manuscripts where patients were recruited for a clinically symptomatic stroke (ischaemic or haemorrhagic), or transient ischaemic attacks. All articles that were judged relevant for this review were finally published in English.


mortality rates, are more often functionally impaired, and should be treated. Research should now focus on a delineation of the concept of poststroke cognitive decline without dementia, which could be a preliminary stage of PSD, and be much more common in practice. A new assessment of the concept of strategic infarcts with modern neuroimaging techniques is necessary. The specific issues of stroke prevention in patients with PSD, and of cholinesterase inhibitors or any other treatment of Alzheimer’s disease or VaD should also be addressed. Finally, epidemiological studies are also necessary to assess the evolution over time of the burden of PSD at the community level, in order to have a better knowledge of the need in terms of resources and its progression over time. Acknowledgments The authors’ work is supported by University Lille II (grant EA2691). Authors’ contributions DL did the literature search, wrote the first draft, wrote the final version and prepared the figure and tables. HH, M-A M-C, and FP did the literature search and approved the final version. Conflicts of interest DL was a member of the steering committee of the SCOPE trial cited in this review and received a consultancy fee paid to his research institution and travel reimbursements. The other authors have no conflicts of interest. References 1 Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349: 1436–42. 2 Hankey GJ, Warlow CP. Treatment and secondary prevention of stroke: evidence, costs, and effects on individuals and populations. Lancet 1999; 354: 1457–63. 3 Leys D, Bandu L, Henon H, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002; 59: 26–33. 4 Mackowiak-Cordoliani MA, Bombois S, Memin A, Henon H, Pasquier F. Poststroke dementia in the elderly. Drugs Aging 2005; 22: 483–93. 5 Rothwell PM, Coull AJ, Giles MF, et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004: Oxford Vascular Study. Lancet 2004; 363: 1925–33. 6 Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDSAIREN International Workshop. Neurology 1993; 43: 250–60. 7 Linden T, Skoog I, Fagerberg B, Steen B, Blomstrand C. Cognitive impairment and dementia 20 months after stroke. Neuroepidemiology 2004; 23: 45–52. 8 Pohjasvaara T, Erkinjuntti T, Ylikoski R, Hietanen M, Vataja R, Kaste M. Clinical determinants of poststroke dementia. Stroke 1998; 29: 75–81. 9 Inzitari D, Di Carlo A, Pracucci G, et al. Incidence and determinants of poststroke dementia as defined by an informant interview method in a hospital-based stroke registry. Stroke 1998; 29: 2087–93. 10 Censori B, Manara O, Agostinis C, et al. Dementia after first stroke. Stroke 1996; 27: 1205–10. 11 Tang WK, Chan SS, Chiu HF, et al. Frequency and determinants of poststroke dementia in Chinese. Stroke 2004; 35: 930–35. 12 Tatemichi TK, Foulkes MA, Mohr JP, et al. Dementia in stroke survivors in the Stroke Data Bank cohort: prevalence, incidence, risk factors, and computed tomographic findings. Stroke 1990; 21: 858–66. 13 Tatemichi TK, Desmond DW, Mayeux R, et al. Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology 1992; 42: 1185–93.

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