Vascular Cognitive Impairment Evidence Tables and Reference List
- Evidence Table 2A Vascular Cognitive Impairment: Screening and Assessment
- Evidence Table 2B Vascular Cognitive Impairment: Cognitive Rehabilitation
- Evidence Table 2C Vascular Cognitive Impairment: Pharmacological Therapy
It has been estimated that 5% of all people over the age of 65 years, in Canada, have evidence of vascular cognitive impairment (VCI). Vascular cognitive impairment refers to cognitive impairment due to all forms of cerebral vascular disease, including stroke, with severity that ranges from mild cognitive impairment to dementia (Gorelick et al., 2011, Rockwood et al. 2000). However, in individuals who have experienced stroke, reported VCI prevalence rates tend to be much greater, depending upon time post stroke, number of strokes and method of assessment, with values ranging from 61% in the acute phase (Hoffmann et al., 2001 to 21%-66% from 3 months to 14 years (e.g., Patel et al., 2003, Delgado et al, 2010, Douiri et al., 2013). While the risk for cognitive impairment is greater following stroke and, certainly, not all individuals with cognitive impairment have dementia, post-stroke cognitive impairment is associated with an increased risk for dementia.
Pendlebury and Rothwell (2009) conducted a systematic review and meta-analysis of 73 published studies examining prevalence and predictors of dementia in individuals with stroke. Overall, pooled prevalence of pre-stroke dementia was 14.4% in hospital-based cohorts (n=22) and 9.1% in community-based studies (n=8). Prevalence of post-stroke dementia ranged from 7.4% in population-based studies of individuals with first-ever stroke and no existing dementia to 41.3% in hospital-based studies of individuals with recurrent stroke (both with and without existing dementia). Rates of dementia were at least doubled following recurrent stroke when compared to first-ever stroke and were higher in hospital-based than in community-based studies. At 3- 6 months, post-stroke incidence of dementia was approximately 20%; this increased linearly at a rate of 3.0% in hospital-based studies of either first or recurrent stroke. Incidence rates were lower in population-based studies of first-ever stroke and when cases with recurrent stroke were excluded.
In the review by Pendlebury and Rothwell (2009), multivariate analyses were identified in 19 studies. From these 19 studies, the most commonly reported independent predictors of post-stroke dementia were older age, lower education level, previous stroke, diabetes, atrial fibrillation, pre-existing cognitive impairment and stroke severity. In summary, Pendlebury and Rothwell (2009) suggest that approximately 10% of patients have existing dementia at the time of stroke. An additional 10% develop new dementia shortly after a first-ever stroke while more than one-third of patients may experience dementia following a recurrent stroke. Recurrent stroke was identified as an important, and commonly cited, predictor of dementia. Gorelick (1997, 2004) reported on the risk factors for vascular dementia in 4 categories: demographic (older age, male sex, lower level of education), atherosclerotic (hypertension, smoking, myocardial infarction, diabetes, hyperlipidemia), genetic (cerebral autosomal dominant arteriopathy with subcortical infarct, leukoencephalopathy, apolipoprotein) and stroke-related (volume of cerebral tissue loss, evidence of bilateral cerebral infarction, strategic infarction, white matter disease).
Cognitive impairment following stroke has been associated with reduction in functional ability, and increased risk for depression (ebrsr.com). Individuals with cognitive impairments have greater functional impairment (Racic et al., 2011, Mok et al., 2004), increased dependency (Narasimhalu et al., 2011), show less clinical improvement (Cristea et al., 2006), and may require more therapy over longer periods of time (Zinn et al. 2004). In addition, the presence of executive dysfunction may have a negative impact on engagement in rehabilitation (Skidmore et al. 2010). A review by Leys et al. (2005) reported that higher rates of mortality have also been found among patients with post stroke dementia in both community-based and hospital-based studies. Overall, mortality rates are reported to be 2 to 6 times higher among individuals with post stroke dementia after adjusting for demographic factors, associated cardiac disease, stroke severity and stroke recurrence (Leys et al. 2005).
At present, there is no ‘gold standard’ for the diagnosis of vascular cognitive impairment. However, it has been recommended that given the anticipated presence of attention and executive dysfunction in cases of vascular cognitive impairment post stroke, any assessment used to detect the presence of VCI be appropriate to the assessment of these domains. As part of the development of the Canadian Stroke Network vascular cognitive impairment harmonization standards, Hachinski et al. (2006) outlined an assessment approach that provided recommended tests for a 5-min, 30-min or 60-minute testing protocol for the screening and assessment of VCI. The 5-minute and 30-minute testing protocols were intended for initial VCI screening (see Table 3 in Hachinski et al., 2006), while the 60 minute battery (Table 2) was provided to allow a breakdown of abilities by domain when needed for rehabilitation or other assessment purposes. Psychometric properties of the recommended tests are reviewed in Hachinski et al., 2006 and further information on screening tests used in stroke populations can be found in Table 2B of these guidelines. More research on the sensitivity and specificity of these protocols in screening for VCI is needed. Overall, the Montreal Cognitive Assessment (MoCA) test appears more sensitive to the presence of VCI compared to the Mini Mental State Examination (MMSE), particularly with mild deficits (e.g., Pendlebury et al., 2012, Godefroy et al., 2011, Toglia et al., 2011, Dong et al., 2010), although equivalence has been noted in other studies, notably with patients of moderate to severe strokes (Dong et al., 2012). Inclusion of the Mini Mental Status Examination in the initial 5-minute Harmonization protocol was rejected, as it does not provide adequate assessment of executive function and is insensitive to mild memory impairment (Hachinski et al. 2006).
Cognitive rehabilitation interventions for VCI within the stroke population, focusing on common deficits of attention, memory or executive function are limited, but growing. In general, interventions may be considered to have one of two objectives: 1) to reinforce or re-establish previous behavioural skills or function (e.g., to remediate with computerized exercises ) or 2) to teach compensatory mechanisms (e.g., strategy training) that may be either internal or external to the individual (Cicerone 2000, 2005). Systematic reviews of cognitive rehabilitation interventions conducted by Cicerone et al. (2000, 2005) and updated in 2011, reported effect sizes for cognitive interventions in attention, visuospatial, language, memory and comprehensive training. Studies of attention or executive function, memory or comprehensive cognitive function were focused more often on individuals with TBI or other brain injury. Although generally positive results have been reported for studies examining the use of attention training, memory strategy training, use of mnemonic devices (e.g. personal pagers), and problem-solving training for study participants who have experienced brain injury (including stroke) evidence from randomized controlled trials specific to the stroke population was more limited (Cicerone et al, 2011; ebrsr.com). More recently, a systematic review by Cha & Kim, 2013 of the efficacy of computer-based cognitive rehabilitation revealed an overall effect size of 0.54 (medium effect), with no difference in acute or chronic stroke patients. Likewise, a recent Cochrane review (Loetscher & Lincoln, 2013) of attention rehabilitation (using various approaches) in stroke reported a significant treatment effect on specific, but not global, attention function, but with no evidence for impact on activities of daily living. In contrast, memory self-efficacy training was reported to improve subjective daily memory reports and quality of life in one RCT with 153 stroke patients in the chronic phase of stroke (Aben et al., 2013). Cicerone et al., 2011 also recommend use of external aids to improve function directly (e.g., alarms, pagers, notebooks) for severe memory impairment following stroke or TBI. In terms of executive dysfunction, while several small studies have reported benefits of meta-cognitive strategy training (Skidmore et al., 2014), goal management training (Levine et al., 2011) and problem solving skill training (Man et al., 2006) in stroke, recent reviews highlight the lack of strong evidence for these interventions at this time (Chung et al., 2013, Poulin et al, 2012).
Finally, physical exercise may also be beneficial for cognitive impairment post stroke as seen in a recent systematic review by Cumming et al., 2012. On the basis of 9 trials investigating the effect of exercise on cognition in stroke patients, they reported a significant, but small, pooled treatment effect (standardized mean difference = 0.2, 95%, CI 0.04 to 0.36, p=0.015).
Cholinergic agents have been used in the treatment of dementia of the Alzheimer’s type. Three such agents, donepezil, rivastigmine and galantamine, have also been investigated for use in the treatment of vascular dementia. Donepezil, a selective acetylcholinesterase inhibitor, has been the subject of 3 large randomized controlled trials (Black et al. 2003, Wilkinson et al. 2003, Roman et al. 2010). A meta-analysis of the first 2 trials demonstrated significant improvements in cognitive and global function, including improvements in the performance of activities of daily living associated with use of donepezil in the treatment of patients with mild to moderate vascular dementia (Passmore et al. 2005). The most recent trial also reported significant improvement in cognitive outcomes associated with treatment (Roman et al. 2010).
In randomized controlled trials, benefits on global function and functional status were not always congruent with benefits on cognition. A study of Vascular Dementia, which include pure and mixed cases showed beneficial effects in both cognition and function, but this was driven by the mixed Alzheimer and vascular cases. The pure Vascular Dementia subgroup showed only modest effects (Erkinjuntti, Lancet 2002, Craig Cochrane review, 2006). There was an attempt to replicate the study in pure Vascular Dementia, but only modest efficacy was shown for the cognitive measure and not for functional outcomes (Auchus, Neurology 2007).
Children and Vascular Cognitive Impairment
Cognitive outcomes for children with stroke must be considered differently. Covert VCI is not a common issue except in select disease states (moyamoya, sickle-cell, small vessel vasculitis). Most importantly, cognitive outcomes must be considered within the context of constantly evolving neurodevelopment. Thus, outcomes must use developmentally and age-appropriate outcome measures. Deficits in cognition and higher brain functions may not be evident until the relevant stage of development is reached, whereby young children “grow into” their deficits over time.[Westmacott et al. 2007a;Westmacott et al. 2009]
About 1 in 3 children with stroke have cognitive deficits at outcome, limiting academic, social, and independent functional success [Friefeld et al. 2004;Nass and Trauner 2004](Carr L 2011). Adverse cognitive outcomes from childhood cerebral sinus venous thrombosis (CSVT) [Wasay et al. 2008;deVeber et al. 2001;Moharir et al. 2010;Berfelo et al. 2010] and hemorrhagic stroke [Blom et al. 2003;Meyer-Heim and Boltshauser 2003] are also common. Overall cognitive function including intelligence, verbal ability, working memory, and processing speed are lower than average in children with stroke. (Westmacott, 2009), [Hetherington et al. 2005; McLinden et al. 2007] [Max 2004; Lansing et al. 2004].
Post-stroke psychiatric/behavioural disorders also appear to be common in childhood stroke (Max, 2002; Elbers 2013). Difficulties with social and behavioral development are also increased in children after stroke with secondary impact on parental mental health (De Schryver, 2002; Goodman, 2000). Limited studies suggest that social function is commonly impaired following stroke in childhood [Mosch et al. 2005]. Rates of potentially treatable Attention Deficit Hyperactivity Disorder (ADHD) are increased [Max et al. 2002;Max et al. 2003;Max et al. 2004], particularly with lesions involving the putamen [Teicher et al. 2000].
Contradicting the idea that the immature brain may be more plastic with a greater capacity for recovery, a younger age at stroke onset may be associated with worse cognitive and behavioural outcomes. (Westmacott, 2009; Everts, 2008)[Stiles 2000;Lansing, Max, Delis, Fox, Lancaster, Manes, and Schatz2004;Westmacott et al. 2007b]. There is also evidence for late emergence of cognitive deficits after perinatal stroke, with IQ measured in the preschool period higher than that measured later.(Westmacott, 2011) About one third of childhood stroke survivors require specialized education (Delsing, 2001). Regular, age-appropriate neuropsychological evaluations should be considered in all at-risk children to determine educational and support needs.