Neuropsychological characteristics of mild vascular cognitive impairment and dementia after stroke

BACKGROUND: Post-stroke cognitive impairment is frequent, with characteristic impairments of attentional and executive performance. OBJECTIVE: The study aims to determine whether the profile and severity of impairment in vascular Cognitive Impairment No Dementia (vascular CIND) is intermediate between that seen in stroke patients without significant cognitive impairment and patients with post-stroke dementia and thus to establish if the potential value of vascular CIND is a useful concept for predicting further cognitive decline and dementia in stroke patients. METHODS: Stroke patients (n=381) > 75 were recruited from representative hospital-based stroke registers in Tyneside and Wearside, UK. Sixty six age matched controls were also recruited. A detailed battery of neuropsychological assessments was completed 3 months post stroke. RESULTS: Deficits of attention (z=5.7; p <0.0001) and executive function (z=5.9; p <0.0001) were seen even in stroke patients without vascular CIND, compared to controls. However, stroke patients with CIND were significantly more impaired again on tests of executive function (z=10.3; p <0.0001) compared to those not meeting CIND criteria; and also had greater impairments of memory (z=10.4; p <0.0001) and language expression (z=10.1; p <0.0001). A similar overall profile of deficits was evident in the CIND and the dementia group, but specific deficits were significantly more pronounced in those with dementia, particularly in orientation (z=7.2; p <0.0001) and memory (z=5.8; p <0.0001). CONCLUSIONS: The current study indicates that attentional and executive impairments are frequent in stroke patients, but deficits of memory, orientation and language are more indicative of CIND and dementia. Further longitudinal studies are required to clarify the relationship between specific lesions and the progression of specific cognitive deficits in post-stroke patients.     

轻度认知损害向老年性痴呆转化的临床研究

目的 研究轻度认知损害(mild cognitive impairment,MCI)向痴呆自然转化过程及多奈哌齐对转化的干预影响.方法 总结98例MCI患者情况,将服用多奈哌齐和未服用任何胆碱酯酶抑制剂的遗忘型MCI(aMCI)及非aMCI患者按年龄、性别、认知减退程度及ApoEε4携带情况分层配对研究,分析各组向痴呆转化率以及MMSE、阿尔茨海默病(AD)评定量表(ADAS-Cog)和aMCI组修订韦氏记忆量表(WMS-R)变化.结果 由aMCI向AD转化率,服用和未服用多奈哌齐组于1年时分别为15.1%和8.3%(P＜0.05),2年时分别为24.2%和12.5%(P＜0.01).由非aMCI向AD转化率,服用和未服用多奈哌齐组,于1年时分别为13.0%和5.5%(P＜0.05),2年时分别为21.7%和16.6%(P＜0.05).服用多奈哌齐6个月时,aMCI组MMSE提高(0.1±1.3)分,对照组下降(0.3±2.4)分;ADAS-Cog下降(1.4±4.7)分,对照组升高(0.03±4.55)分;WMS-R改善(4.8±4.1)分,对照组下降(3.7±5.2)分,治疗组与自然病程对照组比较差异有统计学意义(P＜0.01),并可维持1～2年.多奈哌齐还能延缓携带ApoEε4的MCI患者向AD转化,但与自然病程组比较无统计学意义(P＞0.05),尚有待扩大样本量继续研究观察.多奈哌齐对认知相关区脑萎缩有减缓趋势.结论 本组资料提示,多奈哌齐能推迟MCI向AD转化.     

Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia

BACKGROUND: The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood. OBJECTIVE: To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI. DESIGN AND SETTING: Community-based cohort. PATIENTS: Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis. MAIN OUTCOME MEASURES: Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains. RESULTS: Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation. CONCLUSIONS: The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.     

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.     

Prevalence and characteristics of depression in mild cognitive impairment: the Sydney Memory and Ageing Study

Shahnawaz Z, Reppermund S, Brodaty H, Crawford JD, Draper B, Trollor JN, Sachdev PS. Prevalence and characteristics of depression in mild cognitive impairment: the Sydney memory and ageing study. Objective: Depression might be a risk factor for dementia. However, little is known about the prevalence of depressive symptoms in mild cognitive impairment (MCI) and whether mood or motivation‐related symptoms are predominant. Method: A total of 767 non‐demented community‐dwelling adults aged 70–90 years completed a comprehensive assessment, including neuropsychological testing, and a past psychiatric/medical history interview. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) and Kessler Psychological Distress Scale (K10). Exploratory factor analysis was performed on the GDS and K10 to derive ‘mood’ and ‘motivation’ subscales. Results: A total of 290 participants were classified as having MCI and 468 as cognitively normal (CN). Participants with MCI reported more depressive symptoms, and more MCI participants met the cut‐off for clinically significant symptoms, relative to CN participants. Those with amnestic MCI (aMCI), but not non‐amnestic MCI, had more depressive symptoms and were more likely to meet the cut‐off for clinically significant depressive symptoms, relative to CN participants. Participants with MCI reported more mood‐related symptoms than CN participants, while there were no differences between groups on motivation‐related symptoms. Conclusion: Individuals with MCI, especially aMCI, endorse more depressive symptoms when compared with cognitively intact individuals. These findings highlight the importance of assessing and treating depressive symptoms in MCI.     

Conversion of mild cognitive impairment to dementia: predictive role of mild cognitive impairment subtypes and vascular risk factors

Mild cognitive impairment (MCI) is regarded as a precursor to dementia, but not all patients with MCI develop dementia. We followed up 165 elderly outpatients with MCI for a mean of 3 years. The aims were (1) to investigate the risk of conversion to dementia for different MCI subtypes diagnosed according to standardized criteria (amnestic; impairment of memory plus other cognitive domains; nonamnestic); (2) to assess whether the risk of conversion was affected by several established and emerging vascular risk factors. Forty-eight subjects (29%) converted to dementia, and the risk of conversion was doubled for amnestic MCI with respect to the other subtypes. Independently of MCI subtype, risk of conversion was associated with atrial fibrillation and low serum folate levels. Our results show that current diagnostic criteria for MCI define heterogeneous populations, but some potentially treatable vascular risk factors may be of help in predicting conversion to dementia.     

Assessing cognitive impairment following stroke

The assessment of cognitive function is often neglected following stroke, with no consensus on the optimal method to assess poststroke cognition. We evaluated the ability of a brief protocol to detect cognitive impairment in community-dwelling people with chronic stroke compared to healthy controls and its ability to detect changes in cognition in stroke participants undergoing an exercise intervention. Four tests of cognition were able to detect differences between the groups in the domains of executive function, memory, and information-processing speed. Stroke survivors undergoing exercise over a 5-month period showed significantly improved memory and speed of information processing. Results suggest that exercise may have the potential to improve cognition in long-term stroke survivors and that these tests are sensitive measures of poststroke cognition.     

Amygdala in stroke/transient ischemic attack patients and its relationship to cognitive impairment and psychopathology: the Sydney Stroke Study.

OBJECTIVE: To examine the structural abnormalities in the amygdala in stroke patients and see what contribution the amygdala may make to psychopathology and cognitive dysfunction related to stroke, because the amygdala has important roles in the processing of emotions, cognitive function, and psychiatric disorders. METHODS: The authors assessed 47 stroke/transient ischemic attack (TIA) patients 3-6 months after the event and 54 comparison healthy subjects, using neuropsychological tests, medical and psychiatric examination and magnetic resonance imaging (MRI) brain scans. Volumetric T1-weighted MRI was used to obtain amygdala volumes by manual tracing. RESULTS: Stroke/TIA patients had smaller right amygdalar volume, more white matter hyperintensities (WMHs), and larger lateral ventricles. The amygdala was smaller in stroke/TIA patients with cognitive impairment compared to those without impairment. The right amygdala volume was negatively correlated with visual new learning and not related to depression, anxiety, irritability, agitation or apathy at baseline or 12-month follow-up. However, baseline amygdala volume was negatively correlated with Hamilton depression scores at 12 months in healthy comparison subjects. Hypertension and atrial fibrillation, and to a lesser extent WMHs, were predictors of amygdala volume. CONCLUSION: The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment. This may partly be accounted for by hypertension, white matter lesions, and atrial fibrillation. It is not related to psychopathology except that small amygdalae may increase vulnerability to depression.     

Influence of cognitive impairment on the management of ischaemic stroke

Background

Because of ageing of the population, it is more and more frequent to treat ischaemic stroke patients with pre-stroke cognitive impairment (PSCI). Currently, there is no specific recommendation on ischaemic stroke management in these patients, both at the acute stage and in secondary prevention. However, these patients are less likely to receive treatments proven effective in randomised controlled trials, even in the absence of contra-indication.

Objective

To review the literature to assess efficacy and safety of validated therapies for acute ischaemic stroke and secondary prevention in PSCI patients.

Results

Most randomised trials did not take into account the pre-stroke cognitive status. The few observational studies conducted at the acute stage or in secondary prevention, did not provide any information that the benefit could be either lost or replaced by harm in the presence of PSCI.

Conclusions

There is no reason not to treat ischaemic stroke patients with PSCI according to the currently available recommendations for acute management and secondary prevention. Further observational studies are needed and pre-stroke cognition should be taken into account in future stroke trials.     

Social behavior in mild cognitive impairment and early dementia

Social behavioral abnormalities are commonly seen in the later stages of dementia. However, there has been only limited empirical study of social functioning in the earlier stages of the disease, or in individuals diagnosed with mild cognitive impairment (MCI). The aim of the present study was to test whether these clinical groups show more socially inappropriate and prejudicial behavior relative to controls, as rated by informants. No group differences were identified for ratings of either socially appropriate behavior or stereotyping and prejudice. However, the results also indicated that informants rated participants with dementia as showing the most inappropriate behavior, and that these ratings were related to participants' degree of immediate logical memory impairment, but not to delayed memory recall or to more general neurocognitive decline as indexed by the Mini Mental State Examination. Together, these results have implications for an understanding of some of the changes in social function seen in abnormal adult aging.     

Metabolic syndrome, mild cognitive impairment, and dementia

At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.     

轻度认知障碍与无痴呆型血管性认知障碍患者的神经心理学特征

阿尔茨海默病（AD）和血管性痴呆（vascular dementia，VD）是临床常见的老年期痴呆类型。虽然长期以来受到广泛关注．但对其治疗收效甚微．近年逐渐将研究重点转向对其早期阶段的干预治疗。在这一临床需要下，针对阿尔茨海默病和血管性痴呆分别提出了轻度认知障碍（mild cognitive impairment，MCI）和血管性认知障碍（vascular cognitive impairment，VCI）的概念，力求对患者进行早期识别和干预，以延缓甚至阻止痴呆的发生、发展。     

Fatigue,psychological and cognitive impairment following transient ischaemic attack and minor stroke: a systematic review

Transient ischaemic attack (TIA) and minor stroke are characterized by short‐lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post‐traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random‐effects meta‐analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post‐TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta‐analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini‐Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness of potential subtle but meaningful residual impairments.     

Repetition priming in mild cognitive impairment and mild dementia: Impact of educational attainment

Objective: To examine the role of education on repetition priming performances in healthy aging, mild cognitive impairment (MCI), and mild dementia.

Method: A total of 72 participants (healthy = 27, with MCI = 28, with mild dementia = 17) took part in the present study. Priming was assessed using the Word Stem Completion Test, and delayed and recognition memory was assessed using the Rey Auditory Verbal Learning Test. A multinomial regression analysis was used to examine whether years of education moderated priming and declarative memory performances in predicting group membership.

Results: Priming performances discriminated between individuals with MCI and mild dementia but not between MCI and healthy. Additionally, this effect was most salient in individuals with low levels of education. Education did not moderate explicit memory performances in predicting group membership.

Conclusion: Little is known about the impact of education on priming in verbal memory. Our findings indicate that formal years of education impact priming performances in MCI and individuals with mild dementia, which may have implications for designing interventions targeting “intact” cognitive abilities in these groups.     

Domain-specific trends in cognitive impairment after acute ischaemic stroke

Little is known about the pattern of subacute cognitive domain impairments after ischaemic stroke, nor the temporal evolution of such impairments. Our objective was to investigate the pattern of cognitive impairment in different neuropsychological domains up to a year after ischaemic stroke. We included prospectively collected data from an observational database of stroke patients at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. Patients were categorised into temporal groups according to the time between the index stroke and neuropsychological profiling. The prevalence of impairment in different cognitive domains was then compared between these categories. The final cohort consisted of 209 patients. Frontal executive function, perceptual and nominal skills all showed a strong trend, with levels of impairment of approximately 30 % at <1 month and less than half this at >3 months (p < 0.05). Speed and attention was the most impaired domain, but had the greatest trend for decreasing impairment, from 72.4 % acutely to 37.9 % after 3 months (p < 0.01). By contrast, we found that impairment in visual and verbal memory showed no statistically significant change over time. Our results suggest a domain-specific improvement in cognition after ischaemic stroke. Early assessments may overestimate longer term cognitive deficits, particularly in speed and attention and perceptual functions. The domain-specific improvement patterns may help to inform long-term rehabilitation plans, which should not be based solely on cognitive assessments undertaken within the first month after stroke.