Didier Smadja

Pierre Krolak Salmon
email: pierre.krolak-salmon@chu-lyon.fr

Pierre Krolak

SpecifSpecificities of acute phase stroke management in the elderly

Keywords: Cerebrovascular Disease, Neurorehabilitation, stroke elderly, Epidemiology, Ischemic stroke, Intracerebral hemorrhages

Health professionals are currently facing the challenge of managing an increasing number of old patients presenting with acute stroke, due to rapid aging of the population. Compared to their younger counterparts, elderly patients differ in many ways in the setting of acute stroke.

Apart from a striking high stroke incidence, which increases exponentially as age increases, cardioembolism also becomes, as patients age, the main cause of ischemic stroke. Delirium, which can challenge the diagnosis, is frequent at the acute phase of stroke, and may be related to an underlying dementia, which is almost exclusively observed in the elderly during stroke. At all levels, management of elderly stroke patients is suboptimal, especially when they are cognitively impaired, with insufficiencies including admission to stroke units, applying standards of care and investigation, reperfusion therapy for ischemic stroke, and finally transfer to rehabilitation centers. A paradigm shift must take place to limit age-related discrimination for acute-phase management of stroke.

Epidemiology of stroke

Age is the major non-modifiable risk factor for stroke. Stroke incidence doubles after 55 years [START_REF] Derex | Thrombolysis, stroke-unit admission and early rehabilitation in elderly patients[END_REF]. All epidemiological studies of stroke populations have shown an exponential increase in stroke incidence from age 65, with no apparent limit (Fig. 1) [START_REF] Johnson | Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the global burden of disease study 2016[END_REF][START_REF] Thrift | Global stroke statistics[END_REF]. Thus, after 85, stroke incidence may reach more than 2000 cases/100,000 inhabitants/year, that is to say > 2% per year in very old people [START_REF] Thrift | Global stroke statistics[END_REF]. The global stroke incidence is declining in Europe [START_REF] Béjot | Epidemiology of stroke in Europe and trends for the 21st century[END_REF] and in the USA over the last decades [START_REF] Koton | Trends in Stroke Incidence Rates in Older US Adults: An Update From the Atherosclerosis Risk in Communities (ARIC) Cohort Study[END_REF]. However, because of the worldwide population aging, the absolute number of strokes is expected to dramatically increase in coming years: by 2025, 1.5 million European people will suffer a stroke each year [START_REF] Béjot | Epidemiology of stroke in Europe and trends for the 21st century[END_REF]. We are indeed in a context of a major global increase in life expectancy (LE), with an increase of 5.5 years between 2000 and 2016 [START_REF] Who | Global Health Observatory data, life expectancy[END_REF]. As older people become the part of the population increasing the quickest, the proportion of stroke patients aged over 75 years will increase from 60% recorded in the 1990s to 75% after 2050 [START_REF] Béjot | Epidemiology of stroke in Europe and trends for the 21st century[END_REF]. The risk of dementia also increases with age. In the Canadian Study of Health and Aging, for example, the prevalence of dementia in the 85 years and older group was 28.5%, more than twice that of the 75-to-84-year-old group [START_REF] Ebly | Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging[END_REF]. As a consequence, health professionals are facing the challenge of managing old patients presenting with an acute stroke and concomitant dementia, a feature that deeply influences the management of such stroke patients. To date, an estimated 10% of first-ever stroke patients have an underlying dementia [START_REF] Pendlebury | Prevalence, incidence, and factors associated with prestroke and post-stroke dementia: a systematic review and meta-analysis[END_REF].

Mortality and functional outcomes are worse in the elderly, as much so in patients who are specifically treated and as in others who are not [START_REF] Olindo | Acute stroke in the very elderly: epidemiological features, stroke subtypes, management, and outcome in Martinique, French West Indies[END_REF]. Obviously, frailty and comorbidities of older patients play a major role. Fortunately, there is currently a tendency for better prognosis in stroke victims, both in terms of functional outcome and survival, at all ages, including the elderly [START_REF] Béjot | Trends in stroke incidence and case-fatality rates over a 20-year period (1985-2004) in Dijon, France[END_REF].

Stroke units

Stroke units (SU) reduce mortality, institutionalization and disability, independently of type of stroke (ischemic or hemorrhagic) and stroke severity [START_REF]Organised inpatient (stroke unit) care for stroke[END_REF][START_REF] Candelise | Stroke-unit care for acute stroke patients: an observational follow-up study[END_REF][START_REF] Langhorne | Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis[END_REF], due to interdisciplinary intervention, fast and accurate diagnosis, reperfusion therapies, secondary/tertiary prevention protocols, early rehabilitation and network coordination. Notably, benefit from treatment in a SU is observed equally in patients under or above 75 years of age, although the mean hospital stay is longer after 75 years [START_REF]Organised inpatient (stroke unit) care for stroke[END_REF]. Nevertheless, as depicted in a large English study [START_REF] Rudd | Access to stroke care in England, Wales and Northern Ireland: the effect of age, gender and weekend admission[END_REF], old people, especially those aged 85 or over, have less access to SU care and to early neuroimaging. The authors of this study noted that available information was insufficient to identify any systematic reason, other than advanced age, for not admitting older stroke victims to SU care [START_REF] Rudd | Access to stroke care in England, Wales and Northern Ireland: the effect of age, gender and weekend admission[END_REF]. Concomitant dementia also limits access to the SU. In the Registry of the Canadian Stroke Network, patients with dementia were slightly less likely to be admitted to a SU: 63% vs 67.6%; odds ratio (OR) 0.82 [95% CI 0.70;0.96] [START_REF] Saposnik | Registry of the Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Care and outcomes in patients with ischemic stroke with and without preexisting dementia[END_REF]. This is deleterious for older patients since specific stroke therapies, efficient in this population, require early neuroimaging and management [START_REF] Derex | Thrombolysis, stroke-unit admission and early rehabilitation in elderly patients[END_REF][START_REF] Alshekhlee | Is thrombolysis safe in the elderly? analysis of a national database[END_REF]. In 2008, the European Stroke Organization (ESO) recommended access to SU for all stroke victims (Class I, Level A) irrespective of age [START_REF]Guidelines for management of ischaemic stroke and transient ischaemic attack 2008[END_REF].

Established guidelines are still lacking for stroke patients with dementia [START_REF] Saposnik | Registry of the Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Care and outcomes in patients with ischemic stroke with and without preexisting dementia[END_REF]. Obviously, future guidelines should differentiate stage of dementia, considering that it may be more useful to provide specific treatment for patients with mild rather than severe dementia. On the other hand, the prevalence of so-called "post-stroke dementia" is high in elderly, reaching up to 23% of patients within the first year following a first-ever stroke [START_REF] Béjot | Epidemiology of stroke in Europe and trends for the 21st century[END_REF], a high level of risk expected to decline thanks to specific SU management.

Ischemic stroke

Causes of ischemic stroke

Cardioembolism (CE), mainly represented by atrial fibrillation (AF), is the leading etiology of stroke after 75, and especially so after 85 [START_REF] Leyden | Adelaide stroke incidence study: declining stroke rates but many preventable cardioembolic strokes[END_REF]. Thus, after 85 years of age, CE is noted in around 50% of stroke victims (Fig. 2). To this must be added cases of "cryptogenic" CE in patients with occult, non-identified paroxysmal AF. The trend toward an increasing rate of CE among IS victims as age increases parallels the age-related increase in AF observed in the general population. Indeed, 10% of people aged ≥ 80 years have AF, with an exponential rise in more elderly patients [START_REF] Chao | Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study[END_REF]. Obviously, prevention strategies to detect AF before complications develop so preventive oral anticoagulation can be instituted are crucial owing to the high prevalence of AF in the elderly, the increasing risk of IS with increasing age, and the high severity of CE. In this regard, direct oral anticoagulants (NOACs) are a step in the right direction, since they are much less conducive to intracerebral hemorrhage (ICH), the most daunting hemorrhagic complication of vitamin K antagonists (VKA), the reduction of ICH rate reaching nearly 50% [START_REF] Ruff | Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials[END_REF]. In a large study of patients with AF aged ≥ 90 years, this ICHreduction rate even reached 68% [START_REF] Chao | Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study[END_REF]. However, very old AF patients are still clearly underanticoagulated. In the Darlington AF registry, the majority of very elderly patients with AF (n=561 who were 85 or older) in general practice do not receive oral anticoagulation, and almost 50% received only antiplatelet monotherapy [START_REF] Wolff | Impact of advanced age on management and prognosis in AF: insights from a population-based study in general practice[END_REF]. We are now waiting for new studies focusing the course of NOAC prescriptions among elderly AF patients.

A less common etiology of IS is cancer, which is associated with IS in 5% of cases. Age > 65 has been shown to be the most powerful predictor of active cancer, the mortality being doubled in this context [START_REF] Grazioli | Cancerassociated ischemic stroke: A retrospective multicentre cohort study[END_REF]. The presence of multiple embolic events on neuroimaging, D-dimer elevation, and concomitant venous thromboembolic events were more frequently reported in cancer-associated IS [START_REF] Grazioli | Cancerassociated ischemic stroke: A retrospective multicentre cohort study[END_REF]. A high degree of suspicion should lead to appropriate investigations, especially in old patients affected by a so-called cryptogenic IS.

Delirium at the acute stroke phase

In a systematic review and meta-analysis, delirium was found to affect 10% to 30% of patients in the acute phase of stroke, ischemic or hemorrhagic [START_REF] Shi | Delirium in acute stroke: a systematic review and meta-analysis[END_REF]. Age is a risk factor for post-stroke confusion [START_REF] Shi | Delirium in acute stroke: a systematic review and meta-analysis[END_REF][START_REF] Hénon | Confusional state in stroke: relation to preexisting dementia, patient characteristics, and outcome[END_REF]. The existence of cognitive decline prior to stroke, itself associated with age, is also a major independent risk factor [START_REF] Hénon | Confusional state in stroke: relation to preexisting dementia, patient characteristics, and outcome[END_REF]. Delirium is usually associated with higher mortality, longer hospitalization, and dependency after discharge, as well as lower MMSE scores at six months [START_REF] Hénon | Confusional state in stroke: relation to preexisting dementia, patient characteristics, and outcome[END_REF].

The presence of delirium can be challenging for the diagnosis of acute stroke, especially in older patients, leading to an increased delay in identification and specific treatment. Indeed, a large spectrum of pathological conditions can generate a delirium in elderly, and focal neurological signs of stroke can be masked by alerted mental status. As a rule, the acute occurrence of delirium in an old patient should make doctors suspicious of an acute stroke.

IV Thrombolysis

IV thrombolysis (IVT) by tissue plasminogen activator (tPA) should be performed earlier than 3 hours after IS onset in patients over 80 without any age limitation [START_REF] Wardlaw | Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis[END_REF][START_REF] Powers | Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association[END_REF]. However, between 3 and 4.5 hours, current recommendations continue to exclude patients aged ≥80 years. The results of the IST-3 study showed a good safety profile for IVT in this subgroup of patients up to 6h [START_REF] Sandercock | The benefits and harms of intravenous thrombolysis with recombinant[END_REF], and series of patients that go in the same direction are available [28].

In routine practice, few clinicians still apply age-eligibility selection for IVT, mainly due to the availability of acute stroke magnetic resonance imaging (MRI), which refines the hemorrhagic risk (microangiopathy, microbleeds, cortical hemosiderosis, etc.).

Alongside (or associated with) the age issue, cognitive impairment is a factor limiting the use of IVT. Patients with dementia are less likely to be thrombolyzed than others, even though their stroke-related parameters are favorable [START_REF] Saposnik | Registry of the Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Care and outcomes in patients with ischemic stroke with and without preexisting dementia[END_REF]29,30]. The decision not to propose IVT may be due to the reported over-risk of symptomatic tPA-related ICH (sICH) [29], also because these patients are already disabled, but often, this reluctance is apparently only subjective.

Nevertheless, the immediate benefit of IVT is similar in cognitively impaired patients, although their final prognosis is less good, compared to others [30]. An evaluation of the current state of dependence, often difficult in the acute context of stroke, must be carried out so some cognitive impaired patients can benefit from an effective therapy. Others will be excluded on the grounds of possible therapeutic aggression.

Mechanical thrombectomy

Mechanical thrombectomy (MT) is an effective method to achieve revascularization in patients with acute IS related to a large vessel occlusion (terminal internal carotid, M1/M2 segments of the middle cerebral artery). In 2015, the results of five randomized controlled trials established superiority of MT (with IVT if timing is appropriate) to standard of care in achieving functional independence in selected acute IS patients [START_REF] Goyal | Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials[END_REF], thanks to the new thrombus extraction devices, stent retriever or thrombo-aspiration [START_REF] Lapergue | Effect of Endovascular Contact Aspiration vs Stent Retriever on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER Randomized Clinical Trial[END_REF]. In addition, the initial 6h-window can be extended up to 24 hours, in patients rigorously selected on neuroimaging results including a perfusion study [START_REF] Nogueira | Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct[END_REF][START_REF] Albers | DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging[END_REF]. In contrast to the IVT pivotal trials, the MT trials did not select patients on the age criteria, so that exploitable data on older patients are available. Indeed, MT dramatically improved the prognosis in people over 70 and often over 80 [START_REF] Goyal | Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials[END_REF][START_REF] Calle | Clinical Outcome of Mechanical Thrombectomy for Stroke in the Elderly[END_REF]. In the HERMES meta-analysis based on individual data from the first five pivotal TM trials, a particularly clear clinical benefit was shown in subjects over 80, with an OR =3.7 [2;7] for a good result at three months [START_REF] Goyal | Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials[END_REF]. In real-life studies, consecutive patient series reports confirm the reality of this benefit. However, the overall prognosis, in terms of residual functional disability and mortality, is less good than in younger subjects. One study compared the results of MT in patients aged 80-89 (n=78) with patients aged 90 (n=28): a good clinical result (modified Rankin Scale (mRS)= 0-2 at 3 months) was observed only in 18% vs. 12% (p=0.54), with a mortality rate of 34% vs. 45% (p=0.07) and a sICH rate of 12% vs 20% (p=0.04), in octogenarians and nonagenarians respectively [START_REF] Sussman | Thrombectomy for acute ischemic stroke in nonagenarians compared with octogenarians[END_REF] Another large retrospective cohort study of 203 nonagenarians treated by MT confirmed the very high mortality rate of 48.9% at three months, despite a relatively high (75.9%) successful recanalization rate, mostly due to hospital-acquired infections [START_REF] Meyer | Endovascular Treatment of Very Elderly Patients Aged ≥90 With Acute Ischemic Stroke[END_REF]. In this study, predictors of "good outcome" were the clinical score of neurological severity (NIHSS) at admission and the volume of stroke (ASPECTS) on initial CT: decision making for MT in patients aged 90 and older should be therefore based on a case-by-case basis with regard to initial NIHSS and ASPECTS, together with age-associated comorbidities [START_REF] Meyer | Endovascular Treatment of Very Elderly Patients Aged ≥90 With Acute Ischemic Stroke[END_REF].

Decompressive hemicraniectomy

Decompressive hemicraniectomy (DHC) may be proposed to patients presenting with a malignant IS earlier than 48 h, in patients aged ≤ 60 years, since benefit in terms of functional prognosis and mortality are observed [START_REF] Vahedi | Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomized controlled trials[END_REF]. The efficacy of DHC in stroke patients > 60 years (median age=70 years) was assessed in DESTINI II, a German randomized trial that included 112 patients [START_REF] Jüttler | Hemicraniectomy in older patients with extensive middle-cerebralartery stroke[END_REF]. In the DHC group, 38% survived without severe disability (mRS ≤4) compared to 18% in the control arm, while mortality rates were in favor of DHC (33% of surgical patients vs 70% medical). However, at six months, no patients had functional independence (mRS = 0-2), and at 12 months, only 6% DHC patients had a mRS <4. Therefore, DHC in older patients reduced mortality, but did not provide substantial gain in functional outcomes. A subsequent meta-analysis assessing 14 studies and 747 patients ≥ 60 years found that older patients had 88.3% odds of mRS >3, compared to 66.8% in younger patients [START_REF] Robertson | Decompressive Hemicraniectomy for Stroke in Older Adults: A Review[END_REF].

The decision of DHC in a stroke patient aged > 60 years should be taken at an individual scale, taking into account the physiological age of the patient, comorbidities, patient and close relative wills, multidisplinary team decision. However, in the routine clinical practice, DHC is likely to never been proposed in patients aged > 75 years and/or with dementia.

Intracerebral hemorrhages

Representing 15% of total strokes, ICHs are roughly primary in 85% of cases and secondary in 15%, mostly related to high blood pressure and amyloid angiopathy (AA) in the first case, and vascular lesions, aneurysms, neoplastic lesions, vasculitis and coagulation abnormalities in the second. Alcohol intoxication and tobacco use may increase the risk of ICH, as well as kidney and liver failure [START_REF] Mayer | Treatment of intracerebral haemorrhage[END_REF].

ICH also has peculiarity in terms of etiology in older patients: in fact, lobar ICH, due to amyloid angiography (AA) is a prerogative of the elderly. AA, which is related to amyloid deposits in small and medium caliber cortical and leptomeningeal arteries [START_REF] Qureshi | Spontaneous intracerebral hemorrhage[END_REF], and invariably increases with age, with nearly half of people ≥ 90 years of age showing signs on MRI [START_REF] Ikram | International epidemiology of intracerebral hemorrhage[END_REF]. Nearly 50% of lobar ICH cases are considered to be AA-related (Figure 3) [START_REF] Knudsen | Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria[END_REF]. Lobar ICHs related to AA are often multiple as they may recur with a rate as high as 5% to 15% a year [START_REF] Mayer | Treatment of intracerebral haemorrhage[END_REF][START_REF] Rosand | Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy[END_REF]. The amount of cortical superficial siderosis may be related to the risk of recurrence [START_REF] Linn | Superficial siderosis is a warning sign for future intracranial hemorrhage[END_REF]. AA is often associated with cognitive disorders, and the risk of subsequent dementia is particularly high after lobar ICH in elderly as compared to deep hematomas [START_REF] Moulin | Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study[END_REF].

As a whole, prognosis of ICH is lower than IS since mortality may reach 40% after one month while 80% of ICH surviving patients are significantly impaired after six months [START_REF] Qureshi | Spontaneous intracerebral hemorrhage[END_REF][START_REF] Steiner | European Stroke Organization (ESO) guidelines for the management of spontaneous intracerebral hemorrhage[END_REF]. The factors associated with poor prognosis are large hematoma volume, hematoma expansion, intraventricular hemorrhage, infra-tentorial location, contrast extravasation on computed tomography scan (spot sign), use of anticoagulation, and finally age over 80 years [START_REF] An | Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update[END_REF], as depicted by the ICH score [START_REF] Hemphill | The ICH score: a simple, reliable grading scale for intracerebral hemorrhage[END_REF].

Especially in elderly, a good neuroimaging inventory is necessary in case of ICH. T2* MRI sequences (SWAN, SWI) are required to better evaluate the hematoma and signs of AA like cortical microbleeds and superficial siderosis, as well as white matter changes and associated IS [START_REF] Linn | Superficial siderosis is a warning sign for future intracranial hemorrhage[END_REF]. Moreover, being under anticoagulation is a risk of early hematoma expansion and thus of mortality or worse functional status. However, due to the high prevalence of AF, the elderly are more often under anticoagulated than younger patients, making them at higher risk of anticoagulant-induced ICH. As mentioned above, NOACs are significantly less harmful than VKA [START_REF] Chao | Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study[END_REF][START_REF] Ruff | Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials[END_REF], and mortality seems lightly less in NOACs-related ICH, compared to their counterparts with ICH related to VKA [START_REF] Wilson | Outcome of intracerebral hemorrhage associated with different oral anticoagulants[END_REF][START_REF] Inohara | Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality[END_REF].

Anticoagulation reversal by 4-CCP (15-25 IU/kg) can improve prognosis in people who are treated by VKA, provided it is achieved early [START_REF] Tazarourte | EPAHK study group. Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study)[END_REF]. For NOACs, The French neurovascular society recommends, with a weak level of evidence owing to the lack of data, to check whether anticoagulation medication is correctly taken, and then to administrate the specific antidote idarucizumab for anti-IIa (dabigatran) or non-specific 4-CCP at a high dose (50 IU/kg) for anti-Xa [START_REF] Rosand | Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy[END_REF][START_REF]Hémorragie intracérébrale sous anticoagulants oraux directs[END_REF][START_REF] Steiner | Anticoagulant-Associated Intracranial Hemorrhage in the Era of Reversal Agents[END_REF].

There is no formal indication for surgical removal of the intracranial hemorrhage, especially in the elderly. It may however be discussed in some individual cases presenting with a compressing cerebellar hematoma; suboccipital decompressive craniectomy has been associated with a reduction in mortality compared to expectant medical treatment with or without external ventricular drainage, in all age groups [START_REF] Luney | Acute Posterior Cranial Fossa Hemorrhage-Is Surgical Decompression Better than Expectant Medical Management?[END_REF].

In patients presenting with acute IS and harboring a large amount of radiological AA signs, IVT must be indicated with prudence owing the high intracerebral bleeding risk [START_REF] Charidimou | Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis[END_REF]. Also, the occurrence of an AA-associated IHC in a patient under oral anticoagulant for AF could be a contraindication for later resumption [START_REF] Paciaroni | Should oral anticoagulants be restarted after warfarinassociated cerebral haemorrhage in patients with atrial fibrillation?[END_REF], but there is still controversy on this topic [START_REF] Biffi | Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage[END_REF]. In this latter situation, closure of the left atrium could be a therapeutic alternative to anticoagulation [START_REF] Reddy | 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials[END_REF], in selected old patients with a relatively good quality of life.

Rehabilitation

Post-acute rehabilitation (PAR) is a major component of stroke care. According to current evidence, age per se is not considered a reason for exclusion from stroke rehabilitation, because the oldest-old (≥85 years) could benefit from PAR as effectively as younger stroke patients [START_REF] Saposnik | Investigators of the Registry of the Canadian Stroke Network (RCSN) for the Stroke Outcome Research Canada (SORCan) Working Group. Do all age groups benefit from organized inpatient stroke care?[END_REF]. However, studies of hospital resource use in Western countries show that oldest-old patients admitted to SUs are not investigated nor provided with physical treatment, such as early mobilization (EM), as actively as younger elderly patients because of age discrimination [START_REF] Rudd | Access to stroke care in England, Wales and Northern Ireland: the effect of age, gender and weekend admission[END_REF][START_REF] Russo | Stroke in the very old: a systematic review of studies on incidence, outcome, and resource use[END_REF]. Moreover, access to PAR after SU discharge is also limited. In a very large study including 1055 stroke patients aged ≥65 years admitted to SU and who needed rehabilitation, Forti et al. [START_REF] Forti | Risk of Exclusion From Stroke Rehabilitation in the Oldest Old[END_REF] [START_REF] Forti | Risk of Exclusion From Stroke Rehabilitation in the Oldest Old[END_REF].

In the elderly, cognitive impairment plays an additional role contributing to potential exclusion from PAR [START_REF] Saposnik | Registry of the Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Care and outcomes in patients with ischemic stroke with and without preexisting dementia[END_REF][START_REF] Rabadi | Cognitively impaired stroke patients do benefit from admission to an acute rehabilitation unit[END_REF]. However, despite severe neurologic impairment(s) and disability, cognitively impaired stroke patients make significant functional gains while undergoing rehabilitation and many can be discharged home: in a large study including 668 patients admitted to acute rehabilitation, home discharge was achieved by 78% of cognitively intact patients and by 73% of mildly impaired, 57% of moderately impaired, and 43% of severely impaired patients [START_REF] Rabadi | Cognitively impaired stroke patients do benefit from admission to an acute rehabilitation unit[END_REF]. Obviously, SUs must have specific downstream geriatric pathways, able to provide appropriate rehabilitation for oldest-old and frequently cognitively impaired patients. In this way, discrimination of rehabilitation access for such patients could be limited.

Figure 2 :

 2 Figure 2 : Cardioembolic (atrial fibrillation) ischemic stroke (IS). Female 86 years, acute onset of right hemiplegia and aphasia. MRI showed : DWI: acute left middle cerebral artery (MCA) IS (A) and concomitant acute right superior cerebellar artery IS (B). FLAIR : chronic right MCA-IS (C).

  found that 32.2% of patients were excluded from EM. The OR of EM exclusion was 1.30 [0.76;2.21] for age 75-84 years and 2.07 [1.19;3.59] for age ≥85 years compared to age 65-74 years. Of 656 patients admitted to EM who, at SU discharge, had not yet fully recovered their prestroke functionally status, 18.4% were excluded from PAR. This discrimination involved only patients unable to walk unassisted at SU discharge: OR of exclusion from PAR was 3.74 [1.26;11.13] for age 75-84 years and 9.15 [3.05;27.46] for age ≥85 years compared to age 65-74 years