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Original Research Article

Dement Geriatr Cogn Disord 2011;32:401–407 DOI: 10.1159/000335361

Incidence and Subtypes of MCI and Dementia 1 Year after First-Ever Stroke in Patients without Pre-Existing Cognitive Impairment

Hege Ihle-Hansen Bente Thommessen Torgeir Bruun Wyller Knut Engedal

Anne Rita Øksengård Vidar Stenset Kirsti Løken Morten Aaberg Brynjar Fure

Department of Geriatric Medicine, Asker and Bærum Hospital, Vestre Viken Hospital Trust, Rud , Norway

Background

Post-stroke dementia is defined as any dementia oc-curring after stroke, and includes vascular dementia (VaD), degenerative dementia (mostly Alzheimer’s dis-ease, AD) and mixed dementia (coexistence of vascular and degenerative changes). Vascular risk factors contrib-ute not only to VaD but are present as well in the cascade of Alzheimer pathology proceeding to clinical dementia [1] . Treatment of vascular risk factors in patients with AD without cerebrovascular disease is associated with slower decline in the Mini-Mental State Examination score (MMSE) [2] . In patients with neuropathological signs of AD, the presence of vascular lesions seems to accelerate the onset of clinical symptoms [3] , and the presence of one or two apolipoprotein E (Apo E) 4 alleles is found to be a risk factor for cognitive impairment after stroke [4] . Experimental studies indicate that higher levels of amy-loid in the ageing brain may lead to larger acute infarcts and possibly even cause progression of infarct size over time [5] . Thus, vascular and degenerative changes seem to interact and coexist in post-stroke dementia, resulting in cumulative brain damage and cognitive decline [6–8] .

Better pre- and post-stroke control of vascular risk fac-tors and improved stroke care may contribute to preserv-ing cognitive functioning after stroke [9] . Still, the preva-lence of post-stroke dementia is increasing, probably mainly due to the decline in stroke mortality and increas-

Key Words

Stroke � Cognitive impairment � Dementia

Abstract

Background: Post-stroke dementia is defined as any demen-tia occurring after stroke, and includes vascular, degenerative and mixed dementia. The aim of this study was to assess the incidence of dementia and mild cognitive impairment (MCI) one year after stroke in a population free from pre-stroke cog-nitive decline, and to investigate the different aetiological sub-types of post-stroke dementia and MCI, using a novel method of subclassification in order to separate vascular causes of MCI or dementia from a neurodegenerative disease. Methods: All patients with a first-ever stroke and TIA admitted to the stroke unit of Asker and Bærum Hospital were invited. After 12 months, dementia and MCI were diagnosed. Sub-classifica-tion was made using MRI findings, the results of biomarkers in cerebrospinal fluid and the patients’ clinical cognitive profile. Results: 36 (19.6%) patients developed dementia during the first year after stroke and 69 (37.5%) developed MCI. Fourteen (13.3%) were diagnosed as suffering from degenerative cogni-tive disease, 34 (32.4%) from vascular cognitive disease, and 57 (54.3%) from mixed disease. Conclusion: Fifty-seven percent suffered from cognitive impairment one year after stroke and only one third from isolated vascular cognitive disease. Post-stroke cognitive impairment is complex with a high coexis-tence of vascular and degenerative changes.

Copyright © 2012 S. Karger AG, Basel

Accepted: November 17, 2011 Published online: February 3, 2012

Hege Ihle-Hansen Department of Geriatric Medicine, Asker and Bærum HospitalVestre Viken Hospital Trust, Pb 83 NO–1309 Rud (Norway) Tel. +47 4144 3866, E-Mail hege.ihle-hansen   @   vestreviken.no

© 2012 S. Karger AG, Basel1420–8008/11/0326–0401$38.00/0

Accessible online at:www.karger.com/dem

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ing life expectancy in the population. Sustaining a stroke doubles the risk of dementia [10, 11] . Previous studies have reported different rates of post-stroke dementia; the prevalence estimated 1 year after stroke varies between 7.4% in population-based studies of first-ever stroke, when patients with pre-stroke dementia are excluded, to 41.3% in hospital-based cohorts including recurrent stroke and pre-stroke dementia [12] . Rates of post-stroke cognitive impairment differ even more, from 11.6 to 56.3% [13] , depending on the population under study, cri-teria for cognitive impairment, and the time interval be-tween stroke and testing. Age, a low educational level and pre-stroke cognitive impairment are known risk factors for post-stroke dementia [12, 14] . In addition, diabetes and atrial fibrillation are significantly associated with post-stroke dementia. Surprisingly, other vascular risk factors, such as hypertension, coronary heart disease and smoking, seem to be unrelated to post-stroke dementia [12] . Most predictors relate to stroke per se, i.e. stroke se-verity, stroke recurrence, left hemispheric lesion and haemorrhagic aetiology. Some of the most common com-plications of stroke are also described as risk factors, e.g. incontinence, epileptic seizures, hypotension and deliri-um [12]. However, the pathological mechanisms and the influence of various vascular risk factors on the develop-ment of post-stroke dementia and cognitive impairment are under debate.

Cognitive impairment associated with vascular dis-ease does not necessarily fulfill the traditional criteria for dementia and mild cognitive impairment (MCI), and the term ‘vascular cognitive impairment’ refers to all forms of cognitive impairment linked to cerebrovascular dis-ease [15] . MCI is a condition between normal cognition and dementia [16] , and includes objective deficits relative to norms [17] as well as objective and subjective impair-ments in any of several domains [18] . MCI patients are considered to be at great risk for developing dementia. Few, if any, previous studies have subclassified post-stroke MCI according to aetiology, and no clear criteria exist for diagnosing MCI as vascular, degenerative or mixed. However, in clinical practice, it is crucial to focus on vascular and degenerative components in order to of-fer the patients optimal treatment and thereby improve their prognosis. This aspect will be even more essential when new and effective therapies for early AD become available. Aetiological subclassification of post-stroke de-mentia in a population of first-ever stroke without cogni-tive impairment will also contribute to knowledge re-garding the coexistence of AD in severe vascular cogni-tive impairment.

The aim of this study was to assess the incidence of post-stroke dementia and MCI 1 year after stroke in a population free from pre-stroke cognitive decline. Fur-ther, we wanted to investigate the different aetiological subtypes of post-stroke dementia and MCI using a new method of subclassification.

Methods

Participants All patients with a first-ever stroke or transient ischaemic at-

tack (TIA) admitted to the stroke unit of Asker and Bærum Hos-pital between February 2007 and July 2008 were invited to par-ticipate in the study. Only those patients who survived the acute phase were assessed. The hospital has a policy of admitting all stroke patients directly to the stroke unit. It serves two counties with a total population of approximately 160,000 inhabitants.

We excluded patients with subarachnoid haemorrhage, de-mentia or MCI diagnosed before onset of stroke, cognitive decline as indicated by a score 6 3.44 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) [19] , previous stroke or TIA, patients who did not speak Norwegian and patients with a remaining life expectancy of less than 1 year as estimated by the treating physician. The IQCODE was filled in by the patient’s spouse, a first-degree relative or a close friend. The cut-off ranges of the IQCODE used in different studies have been lower in com-munity samples (3.3–3.6) than in patient samples (3.4–4.0). Ac-cording to Jorm [20] , the best approach is probably to select the cut-off from a study that has a sample close in composition to the population which is being studied. As no clear cut-off exists for the IQCODE in post-stroke samples, we used the cut-off 3.44 to minimize the probability of including patients with a pre-stroke MCI.

Examinations and Assessments The primary distinction between ischaemic and haemor-

rhagic stroke was based on neuroimaging with cerebral CT. Vas-cular risk factors recorded at baseline included treated hyperten-sion before hospitalization, hyperlipidaemia (total cholesterol 1 5.0 mmol/l or low-density lipoprotein (LDL) cholesterol 1 3.0 mmol/l), diabetes mellitus, atrial fibrillation (permanent or par-oxysmal) and current smoking.

At baseline as well as after 12 months, fasting blood samples were collected and analysed, heart rate and blood pressure exam-ined, and electrocardiography performed. Waist and hip circum-ferences, weight and height were measured, and waist-to-hip ratio and body mass index calculated. Smoking habits were recorded.

Cognitive functioning was measured with the MMSE [21] , the Clock Drawing Test [22] , the Trail Making Test A and B (TMT A and B) [23] and the 10-word test (max score 40) including delayed recall from the Repeatable Battery for the Assessment of Neuro-psychological Status [24] . These assessments were performed be-tween days 3 and 7 and at follow-up.

Neurological impairment was measured by the National Insti-tute of Health Stroke Scale (NIHSS) [25] . The neurological ex-aminations were performed on the first day after admittance by an experienced stroke physician. The National Institute of Health

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Stroke Scale was repeated at discharge and at 12 months’ follow-up. We screened for pre-stroke cognitive impairment using the 26-question version of the IQCODE [19] , repeated after 12 months. Activities of daily living were assessed by the Barthel Activities of Daily Living index [26] , and global functioning was measured by the modified Rankin Scale [26] . Patients with ischaemic stroke were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification [27] and the Oxfordshire Com-munity Stroke Project classification [28] by a stroke physician.

At the 12-month follow-up, supplementary investigations in-cluded MRI of the brain, colour duplex of the pre-cerebral arteries and, when possible, lumbar puncture for examination of cerebro-spinal fluid (CSF) biomarkers for neurodegenerative disease.

Cerebral MRI Cerebral atrophy was measured according to the method first

described by Scheltens et al. [29] . Based on the height of the hip-pocampal formation and enlargement of the surrounding CSF spaces, medial temporal lobe atrophy (MTLA) is graded from 0 to 4. MTLA grade 0 = no atrophy; MTLA 4 = highest degree of atro-phy. MTLA 0–1 is considered a normal value.

White matter hyperintensities (WMHs) were quantified with a semi-automated method in the nordiclCE Basis Module as ear-lier described [30] . In the FLAIR images, pixel values in the white matter higher than 2 SD above mean pixel value of the respective slices were defined as WMHs. The total WMH area in all slices were added together and multiplied with slice thickness to obtain total WMH volume (ml). In this material, we defined 1.5 ml as a cut-off volume separating those with minimal WMH from those with moderate and severe ischaemia. This was based on the ob-servation that patients with pencil line lesions along the ventricles and non-confluent small subcortical lesions did not have a total WMH volume exceeding 1.5 ml. Moderate and severe lesions may represent subcortical ischaemic small-vessel disease [31] .

Outcome and Diagnosis Dementia and MCI were diagnosed in accordance with clini-

cal practice at the Memory Clinic in our hospital. For dementia, we used the International Classification of Diseases 10th revision (ICD-10) criteria [32] and for MCI the criteria outlined by Win-blad et al. [18] . The diagnoses were based on the following infor-mation: the patient’s medical history, the IQCODE, results of the routine cognitive assessments and information regarding the pa-tient’s daily functioning – all obtained at 12 months after stroke.

Cognitive tests included MMSE, the Clock Drawing Test, age-adjusted TMT A and B, the 10-word test adjusted for age, and fig-ures from Alzheimer’s Disease Assessment Scale-cognitive sub-scale [33] . In addition, all patients were screened for aphasia using the Ullevaal Aphasia Screening [34] , a simple test for nurses iden-tifying language disability. TMT B was interrupted after 5 min, but we allowed the patients to continue past 5 min if they insisted.

Subclassification was made using all available information in a novel method in order to separate persons with a vascular cause of MCI or dementia from those with a neurodegenerative disease. For both dementia and MCI, we based our subclassification on (1) MRI findings of vascular and degenerative changes in the brain, (2) the results of biomarkers in the CSF and (3) the patients’ clin-ical cognitive profile and vascular risk factors. Consequently, ra-diological findings of WMHs without MTLA were classified as vascular disease, while MTLA without WMHs was interpreted as

being of degenerative origin. A combination of WMHs and MTLA was diagnosed as mixed vascular and degenerative dis-ease. Thus, isolated WMHs had a large impact on the diagnosis of VaD and vascular MCI whereas isolated MTLA had a large impact when a diagnosis of degenerative dementia or degenerative MCI was made. Whenever biomarkers in the CSF were present, patho-logical values of � -protein, phosphorylated � -protein or � -amy-loid peptide supported a diagnosis of degenerative disease. Pre-dominantly cortical symptoms (memory impairment, affected visuospatial function, aphasia, apraxia or neglect) were, when not caused by a cerebrovascular lesion, considered to be compatible with degenerative disease whereas predominantly subcortical symptoms (affecting executive functioning) were interpreted as being most likely of vascular origin [35, 36] . Vascular changes without corresponding subcortical symptoms were interpreted as mixed disease. This resulted in six subgroups: degenerative de-mentia or degenerative MCI , VaD or vascular MCI, and mixed degenerative and vascular dementia or MCI. Thus, the aetiologi-cal subclassification was not determined by the use of standard-ized criteria such as the DSM-IV or ICD-10, but rather by using clinical and paraclinical assessments. This method is based on the assumption that post-stroke MCI must also have a defined cause since there is coexistence of vascular lesions and AD pathology in vascular cognitive impairment [15] . Diagnoses were made in con-sensus meetings by two senior neurologists (B.F and B.T) and one senior geriatrician (A.R.Ø).

Statistics Statistical analyses were performed with the Statistical Pack-

age for Social Sciences (SPSS), version 18.0, using table analyses.

Ethics The study was approved by the Regional Committee for Ethics

in Medical Research and by the Data Protection Authorities. All patients gave their written informed consent before inclusion. First-degree relatives gave consent on behalf of patients with re-duced capacity. This procedure was approved by the Ethics Com-mittee.

Results

Baseline Characteristics After inviting 253 patients, 250 agreed to participate in

the study. Of these, 42 were excluded: 31 did not meet the inclusion criteria (25 had an IQCODE score 6 3.44, 1 did not speak Norwegian, 1 had an infarct in the spinal cord, 1 had suffered a previous TIA, 2 withdrew their consent and 1 died before signing the consent) whereas 11 patients were diagnosed with other diseases than stroke.

Of the remaining 208 patients, 159 (76.4%) had a cere-bral infarction, 33 (15.9%) had suffered a TIA and 16 (7.7%) were diagnosed with a cerebral haemorrhage. Baseline characteristics of the 208 patients are shown in table 1 .

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184 patients completed the follow-up. Of the 22 pa-tients missing, 17 died during the follow-up period where-as 7 patients refused the follow-up and discontinued.

Dementia and MCI According to the ICD-10 criteria, 36 (19.6%) patients

developed dementia during the first year after stoke and 69 (37.5%) developed MCI according to the Winblad cri-teria. Thus, 105 patients (57.1%) of the 184 patients who completed the follow-up developed either dementia or MCI during the first year after stroke.

Subtypes of Dementia and MCI Using our subclassification in the 105 patients with

dementia or MCI, 2 patients (1.9%) had developed degen-erative dementia, 14 (13.3%) VaD and 20 (19.0%), mixed degenerative and VaD. The corresponding figures for the MCI group were 12 (11.4%) degenerative, 20 (19.0%) vas-cular and 37 (35.2%) mixed. All together, 14 (13.3%) of the incident cases were diagnosed as degenerative cognitive disease, 34 (32.4%) as vascular cognitive disease and 57 (54.3%) as mixed degenerative and vascular disease. Ta-ble 2 presents the results of cognitive tests, MRI examina-tion and biomarkers in spinal fluid in the various diag-nostic groups.

According to stroke subtype, 27 (19.3%) with ischaemic stroke developed dementia during the follow-up, includ-ing 10 patients (7.1%) with VaD. In patients suffering from TIA, 2 (7.1%) developed dementia, but none of these de-veloped VaD. Cerebral haemorrhage was followed by de-velopment of dementia in 7 patients (43.8%), including 4 (25%) with VaD. There were no significant differences be-tween the groups. The relationships between stroke sub-types and dementia subtypes are listed in table 3 .

Table 1. B aseline characteristics (n = 208)

Variable

DemographicsMale, n 105 (51%)Mean age8SD, years 72.0812.2Less than 9 years of education, n 50 (24%)

Stroke subtype, nCerebral infarction 159 (76%)TIA 33 (16%)Cerebral haemorrhage 16 (8%)

Risk factors, nHypertension 123 (59%)Hyperlipidaemia 117 (56%)Diabetes 23 (11%)Cigarette smoking (present) 48 (23%)Coronary heart disease 45 (22%)Atrial fibrillation 65 (31)BMI >25 119 (57%)

TOAST classification, nLarge-vessel disease 21 (10%)Cardio-embolic disease 60 (29%)Small-vessel disease 64 (31%)Stroke of undetermined aetiology 63 (30%)

OCSP classification, nTACI 23 (11%)PACI 100 (48%)LACI 61 (29%)POCI 24 (12%)

Topography, nRight hemisphere 80 (39%)Left hemisphere 104 (50%)Cerebellum/brainstem 24 (12%)

AssessmentsNIHSS day 1, mean 4.18 (0.25–5.0)NIHSS at discharge, mean 2.44 (0.0–2.0)BI, mean 17.5 (18.0–20.0)mRS, mean 1.5 (0.0–2.0)

Cognitive assessments (scores)IQCODE (n = 224) 3.0680.19MMSE (n = 214) 26.084.5TMT A (n = 192) 73.7866.7TMT B (n = 162) 152.8889.010-Word test immediate recall (n = 203) 21.287.0710-Word test, delayed recall (n = 201) 4.1582.51

H yperlipidaemia = Total cholesterol >5 mmol/l or LDL cho-lesterol >3 mmol/l; coronary heart disease = previous myocar-dial infarction or present angina pectoris; BMI = body mass in-dex; TOAST = the trial of org 10172 in acute stroke treatment classification; OCSP = Oxfordshire community stroke project classification; TACI = total anterior circulation infarction; PACI = partial anterior circulation infarction; LACI = lacunar circulation infarction; POCI = posterior circulation infarction; NIHSS = National Institute of Health Stroke Scale; IQR = inter-quartile range (shown in parentheses); BI = Barthel Activities of Daily Living Index; mRs = modified Rankin scale; IQCODE = the informant questionnaire on cognitive decline in the elderly.

253 invited

3 declined

17 died7 refused

11 other diseases than stroke31 did not fulfilcriteria

250 included

208 enrolled

184 follow-up

Fig. 1. Patient flow chart.

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We found no difference in the risk of incident cogni-tive impairment (dementia or MCI) according to patho-physiological subgroups of brain infarction as assessed according to the TOAST criteria (p = 0.69). Among pa-tients who had suffered a stroke caused by small-vessel disease, 30/57 (52.6%) developed cognitive impairment, and among those with a stroke caused by large-vessel dis-ease, the corresponding proportion was 47.6%.

Discussion

We observed a remarkably high incidence of dementia and MCI 1 year after the first stroke in a relatively young population without pre-existing cognitive impairment. Only one third of the patients with cognitive impairment developed a purely vascular cognitive disease. Hénon et al. [37] reported two thirds with VaD and one third with possible AD in a similar study. VaD includes, in addition to post-stroke dementia, multi-infarct dementias, hered-itary VaDs and subcortical ischaemic vascular disease [15] . Cerebrovascular diseases are thought to contribute to cognitive decline in the neurodegenerative dementias [15] , and even to enhance the capacity of AD pathology to promote dementia [38] . One possible explanation for the high proportion of AD could be that many patients

had pre-clinical stages of AD that became clinically ap-parent when functional reserves were reduced by the cerebrovascular accident [39, 40] .

The dementia syndrome is characterized by deteriora-tion of cognitive function. Dementia of vascular origin has traditionally been strongly associated with impaired executive functioning, while dementia of degenerative origin more often affects episodic memory, visuospatial function and praxis. All our patients had suffered a cere-brovascular event, and for subclassification, we had to consider the specific vascular lesion as well as WMHs. Subsequently, we took into consideration cortical symp-toms, MTLA and CSF phosphorylated � . MTLA, seen in over half of this sample, is strongly associated with AD [29] . Phosphorylated � , reflecting the formation of tangles

Table 2. C linical profile by aetiological subgroup, 12 months’ follow-up (n = 105)

Assessment Degenerative cognitivedisease (n = 14)

Vascular cognitivedisease (n = 34)

Mixed disease(n = 57)

Score (mean8SD)MMSE 27.383.2 23.189.3 24.486.1Clock drawing test, pathological result 9 (64%) 22 (65%) 34 (60%)10-Word test, immediate recall 22.786.1 20.7810.5 18.586.810-Word test, delayed recall 3.682.7 4.383.1 3.182.4IQCODE 3.280.25 3.580.5 3.480.5ADAS-cog, pathological result 2 (14%) 18 (53%) 31 (54%)TMT A (n = 185) 46.4817.2 76.4866.0 84.9860.3TMT B (n = 160) 142.2862.5 168.6894.4 197.58102.5

Aphasia, UAS <50, n 1 (7%) 11 (32%) 12 (21%)MTLA, right side ≥2, n 8/13 (62%) 15/27 (56%) 35/53 (66%)MTLA, left side ≥2, n 8/13 (62%) 14/27 (52%) 36/52 (69%)WML ≥1.5 ml, n 11/13 (85%) 19 (70%) 46/55 (84%) CSF total � ≥450 ng/l, n 5/6 (83%) 0/9 7/17 (41%)CSF phospho-� >80 ng/l, n 5/6 (83%) 2/9 (22%) 13/17 (76%)CSF A�42 ≤550 ng/l, n 2/6 (33%) 3/9 (33%) 1/17 (6%)

I QCODE = The informant questionnaire on cognitive decline in the elderly; ADAS-cog = Alzheimer’s Disease Assessment Scale-Cognitive Subscale; total � = total �-protein; phospho-� = phosphorylated �-protein; A�42 = �-amyloid peptide.

Table 3. S troke type and subtype of dementia

Diagnosis S ubclassification of dementia P ear-son’s �2

pAD VaD mixed

Ischaemic stroke 2 10 15TIA 0 0 2 0.56Haemorrhagic stroke 0 4 3

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[41] , is considered to be more specific for AD. This sup-ports the high level of mixed dementia and ongoing de-generative disease.

There has been a growing interest in the role of vascu-lar pathology in the pathogenesis of dementia [42] and the contribution of vascular pathologies to dementia se-verity. Further, VaD and AD share many of the same risk factors [43] Traditional post-stroke treatment is directed at vascular risk factors in order to prevent stroke recur-rence. In AD, cholinesterase inhibitors and memantine are given with the purpose to slow the progression of symptoms. It has recently been found that treatment of vascular risk factors may delay cognitive decline in pa-tients with AD without cerebrovascular disease [2] . This highlights the need for optimized post-stroke prevention based on aetiological mechanisms.

Since the pathophysiology of post-stroke dementia is multifactorial [44] , we assume that the same applies to post-stroke MCI. We also postulate that such subclassifi-cation of MCI will improve our ability to focus on both vascular and degenerative preventive strategies at the in-dividual level.

Most previous studies have not recorded pre-stroke dementia. One of six stroke patients is thought to have pre-stroke cognitive impairment [45] , indicating that many cases classified as post-stroke dementia in other studies may, in fact, be due to unrecognized pre-existing dementia. A major strength of our study is the exclusion of patients with pre-existing cognitive decline. The large number of AD and mixed dementias may indicate poor cognitive reserve and pre-clinical degeneration.

We included patients hospitalized with an acute stroke that survived the acute phase and had a remaining life expectancy of more than 1 year. The most severe strokes were therefore not included. We pooled patients with ischaemic and haemorrhagic stroke, and included pa-tients with TIAs. Our results reflect only new-onset de-mentia and MCI after stroke;the incidence of cognitive decline may have been even higher if more severe strokes and fewer TIA cases had been included. The consensus-based diagnoses of dementia and MCI by three experi-enced clinicians improve the validity of our results.

With a cut-off at the IQCODE of 3.44, we may have included some patients with pre-existing symptoms of cognitive impairment. The number of patients with post-stroke MCI may also include pre-stroke cognitive impair-ments not detected by the IQCODE alone. At follow-up, lumbar puncture was performed only in consenting pa-tients who were not taking anticoagulants, leaving just 30%. The use of paraclinical assessments in the diagnosis

of cognitive impairment is still under debate, in particu-lar the overlap between MRI findings regarding degen-erative and vascular changes. Finally, subclassification of MCI was done without stringent, validated criteria, based on the assumption that post-stroke MCI is a pre-stage of post-stroke dementia, and can be classified according to clinical and paraclinical findings.

We found that among first-ever stroke patients with-out known cognitive decline, 57% suffered from cogni-tive impairment 1 year after stroke, and only one third had isolated vascular cognitive disease. In clinical prac-tice, this high coexistence of vascular and degenerative changes indicates that focus on post-stroke cognition should be increased. Subclassification of MCI after stroke may be of importance since this is a ‘brain-at-risk’ stage, and prevention is needed. Post-stroke dementia is a major health concern, and any intervention that may reduce the risk would have a major impact on public health. In the future, to offer modifying treatment, it is of importance to understand the pathophysiology and complexity in post-stroke cognitive impairment.

Acknowledgments

This work has been supported by Helse Sør-Øst RHF and Vestre Viken Hospital Trust. The authors thank the patients par-ticipating in the study and colleagues, physiotherapists and oc-cupational therapists at their hospital. The authors are indebted to the clinical research nurses Nadine Prost, Anne Wergeland and Anne-Mette Brenden and their secretary Kari Wie Skar for excel-lent assistance. Thanks to Sarah Kristine Kaldestad for English proofreading.

Disclosure Statement

The authors have no conflict of interest.

References 1 Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Car-rillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH: Toward defining the preclinical stages of Alzheimer’s disease: rec-ommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s dis-ease. Alzheimers Dement 2011; 7: 280–292.

2 Deschaintre Y, Richard F, Leys D, Pasquier F: Treatment of vascular risk factors is associ-ated with slower decline in Alzheimer dis-ease. Neurology 2009; 73: 674–680.

Dow

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ded

by:

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nbul

Uni

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- 1

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3 Snowdon DA, Greiner LH, Mortimer JA, Ri-ley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alz-heimer disease. The Nun Study. JAMA 1997; 277: 813–817.

4 Wagle J, Farner L, Flekkoy K, Wyller TB, Sandvik L, Eiklid KL, Fure B, Stensrod B, Engedal K: Association between ApoE � 4 and cognitive impairment after stroke. De-ment Geriatr Cogn Disord 2009; 27: 525–533.

5 Cechetto DF, Hachinski V, Whitehead SN: Vascular risk factors and Alzheimer’s dis-ease. Expert Rev Neurother 2008; 8: 743–750.

6 Hachinski V: The 2005 Thomas Willis Lec-ture: stroke and vascular cognitive impair-ment: a transdisciplinary, translational and transactional approach. Stroke 2007; 38: 1396.

7 Leys D, Hénon H, Pasquier F: White matter changes and poststroke dementia. Dement Geriatr Cogn Disord 1998; 9(suppl 1):25–29.

8 Klimkowicz-Mrowiec A, Dziedzic T, Slowik A, Szczudlik A: Predictors of poststroke de-mentia: results of a hospital-based study in Poland. Dement Geriatr Cogn Disord 2006; 21: 328–334.

9 Bejot Y, Aboa-Eboule C, Durier J, Rouaud O, Jacquin A, Ponavoy E, Richard D, Moreau T, Giroud M: Prevalence of early dementia after first-ever stroke: a 24-year population-based study. Stroke 2011; 42: 607–612.

10 Leys D, Hénon H, Mackowiak-Cordoliani MA, Pasquier F: Poststroke dementia. Lan-cet Neurol 2005; 4: 752–759.

11 Savva GM, Stephan BC: Epidemiological studies of the effect of stroke on incident de-mentia: a systematic review. Stroke 2010; 41:e41–e46.

12 Pendlebury ST, Rothwell PM: Prevalence, in-cidence, and factors associated with pre-stroke and post-stroke dementia: a system-atic review and meta-analysis. Lancet Neurol 2009; 8: 1006–1018.

13 Patel MD, Coshall C, Rudd AG, Wolfe CD: Cognitive impairment after stroke: clinical determinants and its associations with long-term stroke outcomes. J Am Geriatr Soc 2002; 50: 700–706.

14 Klimkowicz A, Dziedzic T, Slowik A, Szczudlik A: Incidence of pre- and post-stroke dementia: Cracow stroke registry. De-ment Geriatr Cogn Disord 2002; 14: 137–140.

15 O’Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST: Vascular cognitive impairment. Lancet Neurol 2003; 2: 89–98.

16 Ganguli M, Snitz BE, Saxton JA, Chang CC, Lee CW, Vander BJ, Hughes TF, Loewenstein DA, Unverzagt FW, Petersen RC: Outcomes of mild cognitive impairment by definition: a population study. Arch Neurol 2011; 68: 761–767.

17 Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive im-pairment: clinical characterization and out-come. Arch Neurol 1999; 56: 303–308.

18 Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de LM, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van DC, Visser P, Petersen RC: Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004; 256: 240–246.

19 Jorm AF, Jacomb PA: The Informant Ques-tionnaire on Cognitive Decline in the Elder-ly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med 1989; 19: 1015–1022.

20 Jorm AF: The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a review. Int Psychogeriatr 2004; 16: 275–293.

21 Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.

22 Eddy JR, Sriram S: Clock-drawing and tell-ing time as diagnostic aids. Neurology 1977; 27: 595.

23 Reitan RM: Validity of the trail making test as an indicator of organic brain damage. Per-cept Mot Skills 1958; 8: 271–276.

24 Randolph C, Tierney MC, Mohr E, Chase TN: The Repeatable Battery for the Assess-ment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neu-ropsychol 1998; 20: 310–319.

25 Goldstein LB, Bertels C, Davis JN: Interrater reliability of the NIH stroke scale. Arch Neu-rol 1989; 46: 660–662.

26 Sulter G, Steen C, De KJ: Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke 1999; 30: 1538–1541.

27 Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, III: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35–41.

28 Bamford J, Sandercock P, Dennis M, Burn J, Warlow C: Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521–1526.

29 Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J: Atrophy of medial temporal lobes on MRI in ‘probable’ Alzheimer’s disease and normal ageing: di-agnostic value and neuropsychological cor-relates. J Neurol Neurosurg Psychiatry 1992; 55: 967–972.

30 Stenset V, Bjornerud A, Fjell AM, Walhovd KB, Hofoss D, Due-Tonnessen P, Gjerstad L, Fladby T: Cingulum fiber diffusivity and CSF T- � in patients with subjective and mild cognitive impairment. Neurobiol Aging 2011; 32: 581–589.

31 de Groot JC, de Leeuw FE, Oudkerk M, van GJ, Hofman A, Jolles J, Breteler MM: Cere-bral white matter lesions and cognitive func-tion: the Rotterdam Scan Study. Ann Neurol 2000; 47: 145–151.

32 World Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders: diagnostic criteria for research. Geneva, World Health Organization, 1993.

33 Rosen WG, Mohs RC, Davis KL: A new rat-ing scale for Alzheimer’s disease. Am J Psy-chiatry 1984; 141: 1356–1364.

34 Thommessen B, Thoresen GE, Bautz-Holter E, Laake K: Screening by nurses for aphasia in stroke – the Ullevaal Aphasia Screening (UAS) test. Disabil Rehabil 1999; 21: 110–115.

35 Desmond DW, Erkinjuntti T, Sano M, Cum-mings JL, Bowler JV, Pasquier F, Moroney JT, Ferris SH, Stern Y, Sachdev PS, Hachinski VC: The cognitive syndrome of vascular de-mentia: implications for clinical trials. Alz-heimer Dis Assoc Disord 1999; 13(suppl 3):S21–S29.

36 Moorhouse P, Rockwood K: Vascular cogni-tive impairment: current concepts and clini-cal developments. Lancet Neurol 2008; 7: 246–255.

37 Hénon H, Durieu I, Guerouaou D, Lebert F, Pasquier F, Leys D: Poststroke dementia: in-cidence and relationship to prestroke cogni-tive decline. Neurology 2001; 57: 1216–1222.

38 Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD: Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet 1999; 354: 919–920.

39 Wagle J, Farner L, Flekkoy K, Wyller TB, Sandvik L, Eiklid KL, Fure B, Stensrod B, Engedal K: Cognitive impairment and the role of the ApoE � 4-allele after stroke – a 13 months follow-up study. Int J Geriatr Psychi-atry 2010; 25: 833–842.

40 Ballard CG, Morris CM, Rao H, O’Brien JT, Barber R, Stephens S, Rowan E, Gibson A, Kalaria RN, Kenny RA: APOE � 4 and cogni-tive decline in older stroke patients with ear-ly cognitive impairment. Neurology 2004; 63: 1399–1402.

41 Kester MI, Scheltens P: Dementia: the bare essentials. Pract Neurol 2009; 9: 241–251.

42 Viswanathan A, Rocca WA, Tzourio C: Vas-cular risk factors and dementia: how to move forward? Neurology 2009; 72: 368–374.

43 Kivipelto M, Helkala EL, Laakso MP, Han-ninen T, Hallikainen M, Alhainen K, Soin-inen H, Tuomilehto J, Nissinen A: Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population-based study. BMJ 2001; 322: 1447–1451.

44 Hénon H, Pasquier F, Leys D: Poststroke de-mentia. Cerebrovasc Dis 2006; 22: 61–70.

45 Hénon H, Pasquier F, Durieu I, Godefroy O, Lucas C, Lebert F, Leys D: Preexisting de-mentia in stroke patients. Baseline frequen-cy, associated factors, and outcome. Stroke 1997; 28: 2429–2436.

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