Non-cognitive psychiatric symptoms in vascular and Alzheimer brain disease

Psychiatric symptoms, other than dementia, are compared in two groups of mental hospital patients who came to autopsy and had complete brain examination. One group had Alzheimer brain changes with no cerebral infarction. The other group had cerebral infarction with no Alzheimer brain changes. Onset with a non-dementing paranoid illness after the age of 50 was commoner in the Alzheimer group. There was no predominance of affective symptoms in either group. Suddenness of onset of psychosis distinguished the infarct cases, even in cases where there was no neurologically evident stroke, and when there were long time intervals between onset and death. Those destined to suffer Alzheimer brain changes had a less sudden onset, fewer discharges and rehospitalizations and more frequent transition to dementia.§     

Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability

Vascular dementia is the second most common type of dementia after Alzheimer’s disease (AD). Subcortical ischemic vascular disease refers to a form of vascular cognitive impairment characterized by the presence of diffuse white matter hyperintensities (WMHs) and multiple lacunar infarcts. These neuroimaging findings are mainly caused by cerebral small-vessel disease (cSVD) and relate to aging and cognitive impairment, but they can also be silent and highly prevalent in otherwise healthy individuals. We aimed to review studies on blood and cerebrospinal fluid (CSF) markers related to the presence of WMHs and lacunar infarcts that have been conducted in the past in large population-based studies and in high-risk selected patients (such as those with vascular risk factors, vascular cognitive impairment, or AD). Relevant associations with the presence and progression of cSVD have been described in the blood for markers related to inflammatory processes, endothelial damage and coagulation/fibrinolysis processes, etc. Also, different combinations of CSF markers might help to differentiate between etiologic types of dementia. In the future, to translate these findings into clinical practice and use biomarkers to early diagnosis and monitoring vascular cognitive impairment would require the replication of candidate markers in large-scale, multicenter, and prospectively designed studies.     

急性缺血性脑血管病诊治时间分析

本文报道121例急性缺血性脑血管病患者诊治时间的临床分析，结果显示发病至就诊时间≤6h者，约占总例数的19％；6～12h者，约占总例数的10．7％；12～24h者，约占总例数的14．9％；24～48h者，约占总例数的15．7％；＞48h者，约占总例数的39．7％。不同职业及文化程度的患者，其发病至就诊时间和入院至治疗时间有显著差异。提出了缺血性脑血管病早期诊治的迫切性，认为应把缺血性脑血管病作为一医疗急症，应受到如心脏病发作那样重视的紧急处理。     

Chitotriosidase and inflammatory mediator levels in Alzheimer's disease and cerebrovascular dementia

Inflammation has been reported to be involved in the pathogenesis of cerebrovascular dementias (CvDs). This study investigated the involvement of Chitotriosidase (ChT), a chinolitic enzyme mainly produced by activated macrophages, in the pathophysiology of Alzheimer's disease (AD) and ischemic CvD. In addition, the levels of interleukin (IL)-16, IL-18, transforming growth factor (TGF)-beta1 and superoxide anion (O2(-)) were determined to evaluate the relationship between ChT levels, these cytokines and oxidative stress in both AD and ischemic CvD patients. The levels of ChT and IL-16, IL-18, and TGF-beta1 mRNA were investigated using quantitative real-time polymerase chain reaction on macrophages of peripheral blood of 40 patients with AD, 40 patients with ischemic CvD and 40 non-demented age-matched subjects. The results show that ChT, IL-16 and O2(-) levels significantly increased in ischemic CvD patients compared with AD patients and were significantly and positively correlated with IL-18 and O2(-). The production of IL-18 was increased in both AD and ischemic CvD patients. TGF-beta1 expression was higher in AD patients and was inversely correlated with the expression of ChT, IL-16 and IL-18, respectively. In non-demented age-matched subjects no significant changes in ChT and IL-16, IL-18, and TGF-beta1 expression were found. Our results indicate that ChT, IL-16, IL-18 and TGF-beta1 are increased in ischemic CvD and AD, confirming that the immune system may play an important role in the development and progression of neurodegenerative disorders. In addition, the present findings suggest that ChT could also play a crucial role in pathological conditions such as CvD in which the inflammatory process is activated.     

缺血性脑血管病患者颈动脉粥样硬化与血浆炎性细胞因子的关系

目的探讨缺血性脑血管病(ICVD)患者颈动脉粥样硬化与血浆炎性细胞因子的关系。方法采用酶联免疫吸附法测定64例ICVD患者血浆白介素(IL)-6、基质金属蛋白酶(MMP)-8及可溶性白细胞分化抗原配体-40(sCD40L)的水平;彩色超声检测双侧颈部动脉血管硬化程度,并与非ICVD患者(对照组)进行比较;分析血浆IL-6、MMP-8及sCD40L水平与颈动脉粥样硬化程度的关系。结果与对照组相比,ICVD组血浆IL-6、MMP-8、sCD40L水平明显升高(均P<0.01);血浆IL-6、MMP-8、sCD40L水平与颈动脉粥样硬化程度关系密切。结论血浆炎性细胞因子水平与颈动脉粥样硬化程度以及颈动脉斑块进展有密切关系。     

灌注磁共振成像在缺血性脑血管病外科治疗中的作用

目的探讨灌注磁共振成像(PWI)在缺血性脑血管病外科治疗中的作用。方法回顾性分析24例缺血性脑血管病患者的临床及影像学资料。并对外科治疗患者术前、术后均行PWI检查,以比较患者的脑血流灌注情况。结果本组患者中,单侧颈内动脉严重狭窄或闭塞9例,单侧大脑中动脉严重狭窄或闭塞8例,颅内、外动脉系统多发性狭窄或闭塞5例,烟雾病2例。术前PWI显示局部脑血流量(rCBF)正常、平均通过时间(MTY)升高15例,rCBF降低、MTT升高8例,rCBF和MTT均正常1例。23例接受外科治疗,其中13例行支架血管成形术,4例行颈动脉内膜切除术,6例颞浅动脉一大脑中动脉(STA—MCA)动脉吻合术;术后PWI改善19例(82．6％),其中支架血管成形术12例(92．3％),颈动脉内膜切除术4例(100％),STA—MCA吻合术3例(50％)。结论PWI可以评价缺血性脑血管病患者的脑血流灌注异常及外科治疗后有效地改善脑血流灌注的情况。     

Association between psychological measures with inflammatory anddisease-related markers of inflammatory bowel disease

Objective: This study aimed at investigating the associations between inflammatory mediators, symptoms and psychological disturbances in inflammatory bowel disease (IBD) patients.

Methods: IBD patients and patient controls were examined during a single visit to a gastroenterology clinic. Disease activity was assessed using the Mayo index for ulcerative colitis (UC), inflammatory bowel disease questionnaire (IBDQ), Crohn’s disease activity index (CDAI) and Crohn’s disease endoscopic index of severity (CDEIS). Gene expression of inflammatory mediators were measured in intestinal biopsies and whole blood samples along with circulating concentrations of interleukin (IL)-6, interferon (IFN)γ, C-reactive protein (CRP), kynurenine and tryptophan. Validated depression, anxiety and quality of life scores were used to assess psychological well-being.

Results: Patients who were symptomatic had the highest depression and anxiety scores, together with increased intestinal expression of IL-1β, IL-6 and matrix metalloproteinase-9, increased circulating IL-6 and CRP, and an increased circulating kynurenine:tryptophan ratio. Increased Hamilton depression (HAM-D) scores in IBD patients were observed independent of the psychological impact of acute symptoms.

Conclusions: Active IBD is associated with symptoms of depression and anxiety and with a raised circulating inflammatory mediator profile. Patients with active IBD exhibiting psychological symptoms should undergo psychological evaluation to ensure the psychological aspects of the condition are considered and addressed.     

Anosognosia in Alzheimer's disease: association with patient characteristics, psychiatric symptoms and cognitive deficits

Anosognosia is one of the major problems in the treatment and care of Alzheimer's disease (AD) patients. The aim of the study was to determine the patient characteristics, psychiatric symptoms, and cognitive deficits associated with anosognosia, because these are currently poorly understood. Eighty-four patients who met the National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD were examined for anosognosia based on the difference between questionnaire scores of the patient and their caregiver. The relationship of anosognosia with patient characteristics (age, age at onset, duration of illness, education, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hyogo Activities of Daily Living Scale (HADLS)), psychiatric symptoms (Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS)), and cognitive function (Digit Span, Word Fluency Test, Trail Making Test, Stroop Test, Raven's Coloured Progressive Matrices Test) were studied. Anosognosia showed positive correlations with age, age at onset, duration of illness, CDR, HADLS, and NPI disinhibition, and negative correlations with MMSE and GDS. Regarding cognitive function, only Part III of the Stroop Test was a predictor of anosognosia. The severity of anosognosia increased with disease progression and with a later age at onset. Subjective complaints of depression requiring self-monitoring of mood tended to decrease and, in contrast, inhibition of socially unsuitable behavior became more difficult as anosognosia worsened. Regarding cognitive function, anosognosia appeared to be associated with response inhibition impairment. Both disinhibition, as a psychiatric symptom, and response inhibition impairment are known to be correlated with disturbance of orbitofrontal function, which therefore may be associated with anosognosia.     

Dementia with cerebrovascular disease: the benefits of early treatment

Patients with vascular dementia (VaD) and Alzheimer's disease with cerebrovascular disease (AD + CVD) have dementia associated with underlying CVD. Although diagnosis of VaD is challenging, VaD is typically characterized by a stepwise progression of dementia that is closely associated with stroke and focal neurological findings, and a symptom profile that often includes executive dysfunction leading to decreased ability to perform instrumental activities of daily living (IADL). In contrast, AD + CVD patients typically present with progressive deterioration of cognition/memory that may also be influenced by concurrent cerebrovascular events. Early diagnosis and intervention are desirable to prevent further decline due to subsequent vascular events. Management of CVD can limit deterioration of cognitive symptoms in VaD patients, and treatment benefits with cholinesterase inhibitors may be realized as improvement above baseline levels in dementia symptoms. Results from a combined analysis of two 24-week, placebo-controlled clinical trials show that donepezil-treated VaD patients improve in cognition, global function, and performance of IADL. In contrast, AD + CVD patients may continue to decline despite management of CVD, and treatment benefits should be recognized as initial improvements followed by stabilization or slowed decline of dementia symptoms over time. In post-marketing studies, donepezil-treated AD and AD + CVD patients show similar benefits in cognition, global function, and quality of life. The results of these studies support the use of donepezil in treatment of patients with VaD or AD + CVD.     

Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome

Objectives: To identify non-demented individuals with cognitive impairment due to a cerebrovascular etiology among those coming to observation of a memory clinic and to describe their clinical features and outcome. Methods: Patients were enrolled in a prospective study on early cognitive impairment carried out in a Memory Clinic. Mild cognitive impairment of the vascular type (MCI-V) was defined based on modified criteria for subcortical vascular dementia (SVD) by Erkinjuntti and colleagues. Twenty-nine patients with MCI-V (age 78 ± 7, Mini Mental State Exam (MMSE) 24 ± 3) were compared with 14 with mild cognitive impairment of degenerative etiology (MCI) based on the Mayo Clinic criteria (age 72 ± 9, MMSE 25 ± 2), and to 21 patients with frank SVD (age 80 ± 6, MMSE 21 ± 3). Patients were followed over time for 32 ± 8 months. Results: MCI-V patients had a neuropsychological profile characterized by poor performance on frontal tests (Wisconsin card sorting and word fluency) and neurological features of parkinsonism without tremor (impairment of balance and gait). Of those followed for at least 40 months, 50 % of patients with MCI-V and SVD had died, while all MCI patients were still alive (P = 0.03). Of those alive, 68 % of the MCI-V, 52 % of the SVD, and 17 % of the MCI patients had reached one of the following outcomes at 40 months: nursing home placement, functional loss, and cognitive deterioration (P = 0.02). Conclusions: Patients with MCI-V have a distinctive clinical picture and can be identified in a clinical setting. Because of the high frequency of adverse outcomes, very early preventive measures need to be devised. Received: 27 July 2001, Received in revised form: 22 February 2002, Accepted: 22 April 2002 Correspondence to Giovanni B. Frisoni, MD     

Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan

We describe 2 normotensive sisters presenting slowly progressive dementia associated with acute or subacute focal neurological symptoms, unilateral or bilateral motor signs, and dysarthria. Their father, who died in the seventh decade, had a similar clinical picture. Computerized axial tomography (CT) scan of the head showed symmetrical hypodensities in the periventricular white matter and mild to moderate hydrocephalus. In these patients a diagnosis of Binswanger's disease was based on the clinical features supported by white matter changes on CT scan. Our study suggests that genetic factors may play a role in the etiology of Binswanger's disease.

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Sommario Descriviamo due giovani sorelle normotese affette da demenza lentamente progressiva associata a sintomi neurologici focali ad insorgenza sia acuta che subacuta. Un quadro clinico simile era presente nel padre deceduto all'età di 70 anni.La TAC cranica mostrava nelle due pazienti ipodensità simmetriche della sostanza bianca perventricolare con idrocefalo moderato.In questi pazienti una diagnosi di malattia di Binswanger fu fatta in base al quadro clinico ed alle lesioni riscontrate alla TAC. Il nostro studio dimostra la possibilità che fattori genetici siano responsabili di alcune forme di malattia di Binswanger soprattutto in pazienti normotesi, giovani e senza fattori di rischio per malattie cerebrovascolari.

     

Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer's disease with cerebrovascular disease.

The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD) with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and functional benefits in these populations. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). Galantamine (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older dementia patients, included depression, agitation, and insomnia. Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of galantamine were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function.