Decreased Vasomotor Reactivity in Alzheimer's Disease

Background

Reduced cerebral blood flow and microvascular abnormalities have been suggested as the vascular pathogenesis of Alzheimer''s disease (AD). Transcranial Doppler sonography (TCD) can be used as a noninvasive method for measuring cerebral vasomotor reactivity (VMR) which represent the capability of arterioles to dilate and constrict in order to maintain cerebral blood flow.

Objective

The objective of this study was to determine whether VMR is decreased in AD patients. Methods: Seventeen consecutive patients who met NINDS-ADRDA criteria for AD, and 17 age- and sex-matched controls were included in this study. MRI and MRA were performed for the grading of white-matter lesions. Patients with cerebral infarct or stenosis of the middle cerebral artery (MCA) were excluded. The fixed TCD probe was used to monitor the mean flow velocity (MFV) in the MCA. A 6-L rebreathing bag was applied to patients for at least 5 minutes to elevate the CO₂ concentration, which was continuously monitored with a capnometer. VMR was calculated as the percentage change in the MFV.

Results

Baseline characteristics - including cerebrovascular risk factors, grades of white-matter lesions, baseline MFV, and pulsatility index - did not differ between the two groups. Mini-Mental State Examination score was significantly low in AD group (20.5 vs. 27.5, p<0.05). VMR was significantly reduced in AD group both in the right-side (24.5% vs. 36.6%, p<0.05) and left-side (20.7% vs. 34.1%, p<0.05) MCAs.

Conclusions

Our finding that VMR is reduced in AD may be suggestive of underlying microangiopathic mechanism in AD patients. Future studies should check the validity of these experimental and hypothesis-generating pilot results.     

Usefulness of a blood flow analyzing program 3DSRT to detect occipital hypoperfusion in dementia with Lewy bodies

In the latest criteria for the clinical diagnosis of dementia with Lewy bodies (DLB), supportive features include generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity. In this study, we investigated the usefulness of a cerebral blood flow (CBF) quantification program '3DSRT' in detecting occipital hypoperfusion in DLB. Twenty two patients with probable DLB, 38 patients with probable Alzheimer's disease (AD) and 16 normal controls underwent brain perfusion SPECT. Compared with AD, DLB patients had a bilateral lower CBF in the posterior cerebral segments. The correlation of clinical symptoms and brain blood perfusion was examined by dividing the subjects into subgroups. DLB patients with Parkinsonism, when compared to non-Parkinsonism subgroup, had a lower CBF throughout the cerebrum with statistical significance in the posterior cerebral segments. The quantitative analysis of brain perfusion SPECT by 3DSRT could be a useful supportive measurement in the diagnosis of DLB.     

Vasomotor reactivity in dementia of alzheimer type

The objective of this study was to examine the cerebral blood flow and the vasomotor function of CO₂-responsive intracerebral vessels in Alzheimer's disease. Patients met DSM-III-R criteria for dementia of Alzheimer type and had neither symptoms nor signs of cardiovascular or cerebrovascular disease. Blood flow velocities in both middle cerebral arteries (MCA) were recorded using transcranial Doppler sonography during hypercapnia, normocapnia and hypocapnia. Several psychometric tests were performed. Patients' age, disease duration and severity of dementia did not correlate with vasomotor reactivity. Exploratory analysis revealed that mean flow velocities under hypercapnia correlated with severity of dementia and with patient's age. This suggests that the disease process does not influence the autoregulative function of small resistance vessels as assessed by CO₂ challenge. However, the excess reduction of the highest flow velocities measured during maximal CO₂ stimulation indicates that the number of small capillaries are diminished, or alternatively that the diameters of these capillaries are reduced in Alzheimer's disease.     

TCD对颈内动脉中度及重度狭窄患者脑血流动力学的评估价值

目的应用经颅多普勒超声(transcranial doppler,TCD)评价颈内动脉中度及重度狭窄患者的脑血流动力学变化。方法经数字减影血管造影(digital subtraction angiography,DSA)确诊单侧颈内动脉中度及重度狭窄的患者69例,采用TCD检测其大脑中动脉血流参数,评价其侧支循环开放情况和脑血流储备能力(CRV)。结果 TCD显示侧支循环开放者患侧收缩期峰时血流速度(Vs)、搏动指数(PI)及CVR明显高于无侧支循环开放患者(P0.05),颈内动脉中度狭窄组患侧收缩期峰时血流速度(Vs)、PI值及CVR明显高于重度组(P0.05)。结论颈内动脉狭窄时侧支开放可以改善远端血流动力学指标,但改善程度有限。TCD可检测颈内动脉狭窄患者颅内血流动力学变化,评价颅内侧支循环的建立情况,为临床治疗和评估提供可靠依据。     

A transcranial Doppler study of basilar hemodynamics in progressive carotid artery disease

Abstract

In carotid artery disease (CAD) the basilar artery (BA) may act as an important intracranial collateral to supply hypoperfused middle cerebral artery (MCA) territories. Transcranial Doppler studies were performed to study the dependency between BA hemodynamics in relation to the MCA perfusion status. BA and MCA blood flow velocities (BFV), pulsatility indices (API) and cerebrovascular reactivity (CVR) were assessed in 40 patients with a progressive MCA hypoperfusion due to progressive CAD. All patients had patent cervical segments of their vertebral arteries with an antegrade vertebral flow profile. Duplex studies were performed to diagnose the severi~ of CAD. Hypoperfusion of the MCA was diagnosed by the degree of vasoparalysi assessed by a Diamox procedure. Analysis showed that the basilar BFV significantly increased in cases of progressive CAD; the basilar PI decreased but the basilar CVR remained unchanged. However, in cases of bilateral hemodynamic significant CAD and bilateral exhausted CVR in the MCA territory, the basilar artery did not exhibit an increase of BFVs or a decrease of the basilar PI, but the basilar CVR showed a significant decrease. Basilar artery CVR is not impaired if this artery has a function as intracranial collateral in CAD. However in cases of bilateral hypoperfused MeA territories the basilar artery does not function as a collateral pathway. The basilar CVR declines under these circumstances which merely reflects the exhausted hemodynamics in the anterior/posterior borderzones. This situation might lead to an increased stroke risk in the distal basilar supply zones. [Neural Res 1998; 20: 493-498]     

Cerebral blood flow regulation during cognitive tasks: effects of healthy aging

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30+/-1.5 years; 15 old, 74+/-1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA>PCA BFV during the WSC task and PCA>ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA>ACA BFV during the VS task, they did not have ACA>PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks.     

体外循环心内直视手术时脑血流速度改变的研究

目的研究体外循环心内直视手术期间脑血流速度的变化和影响因素。方法在１７例患者心内直视手术时应用双通道经颅多普勒于术中动态监测大脑中动脉血流速度的变化。结果在体外循环转流期间，脑血流速度降低并随平均动脉压的改变有一定波动，血流频谱呈锯齿状。结论ＴＣＤ动态监测脑血流速度在体外循环心脏手术过程中对了解脑灌注的改变有一定价值     

SPECT findings in Alzheimer's disease and Parkinson's disease with dementia

We examined, with single photon emission tomography (SPECT) and (^99mTc)-HMPAO, 18 patients with idiopathic Parkinson's disease and no dementia (PD), 12 patients with PD and dementia, 24 patients with probable Alzheimer's disease (AD) and 14 controls. While the three patient groups showed significantly lower perfusion in frontal inferior and temporal inferior areas as compared to controls, both demented groups showed significantly more severe bilateral hypoperfusion in superior frontal, superior temporal and parietal areas as compared to non-demented PD patients and controls. On the other hand, no significant differences in cerebral perfusion were found between patients with AD and patients with PD and dementia. In conclusion, our findings demonstrated specific but similar cerebral perfusion deficits in demented patients with either AD or PD.     

Sundown syndrome in persons with dementia: an update

"Sundowning" in demented individuals, as distinct clinical phenomena, is still open to debate in terms of clear definition, etiology, operationalized parameters, validity of clinical construct, and interventions. In general, sundown syndrome is characterized by the emergence or increment of neuropsychiatric symptoms such as agitation, confusion, anxiety, and aggressiveness in late afternoon, in the evening, or at night. Sundowning is highly prevalent among individuals with dementia. It is thought to be associated with impaired circadian rhythmicity, environmental and social factors, and impaired cognition. Neurophysiologically, it appears to be mediated by degeneration of the suprachiasmatic nucleus of the hypothalamus and decreased production of melatonin. A variety of treatment options have been found to be helpful to ameliorate the neuropsychiatric symptoms associated with this phenomenon: bright light therapy, melatonin, acetylcholinesterase inhibitors, N-methyl-d-aspartate receptor antagonists, antipsychotics, and behavioral modifications. To decrease the morbidity from this specific condition, improve patient's well being, lessen caregiver burden, and delay institutionalization, further attention needs to be given to development of clinically operational definition of sundown syndrome and investigations on etiology, risk factors, and effective treatment options.     

Modeling the dementia epidemic

The incidence of dementia increases steeply with age in older people, although from the tenth decade the slope may be smoother, perhaps reflecting different pathological processes in the oldest old. The prevalence depends upon interaction of age with other factors (e.g., comorbidities, genetic or environmental factors) that in turn are subject to change. If onset of dementia could be postponed by modulating its risk factors, this could significantly affect its incidence. Analysis of risk and protection factors should take into account the critical period during which these factors play a role. For example, the impact of education and diabetes mellitus occurs in early- and midlife, respectively, while maintaining optimal physical and mental activity and controlling vascular factors later in life may slow the rate of cognitive decline. Modifying factors need to be evaluated for different clinical groups, taking into account genetic background, age, and duration at exposure. The aim of the present article is to try to take stock of epidemiological data concerning factors affecting the prevalence of dementia and predict future developments, as well as to look for possible interventions that could affect outcome.     

Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD-d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD-d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD-d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor-subscale scores between DLB and PD-d patients. DLB and PD-d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD-d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD-d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.     

Inflammatory markers and the risk of dementia and Alzheimer's disease: A meta-analysis

Introduction

Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of developing dementia.

Cerebral hemodynamic response induced by the Tower of Hanoi puzzle and the Wisconsin Card Sorting test

Transcranial Doppler sonography (TCD) was applied in normal subjects to investigate the effect of prefrontal functions like the Tower of Hanoi (TOH) task and the Wisconsin Card Sorting test (WCST) on cerebral hemodynamics. In 20 healthy volunteers, left and right middle cerebral artery (MCA) and anterior cerebral artery (ACA) were insonated. The TOH task and the WCST were administered while cerebral blood flow velocity (CBFV) was registered. Each test was repeated once per artery pair. There was a visuomotor test to control the motor and visual stimulations. Three phases of CBFV time course were detected: an initial peak within 5 s, a following decrease within 25 s and a steady state beginning at 40 s. The TOH task, WCST and visuomotor tests had different mean CBFV during the initial peak (MCA: P<0.05; ACA: P<0.05) as well as for the decrease (ACA: P<0.01) and the steady state (MCA: P<0.01; ACA: P<0.01). The TOH showed an increased mean CBFV as compared with the WCST during the steady state (MCA: P<0.01; ACA: P<0.05). However, temporal modulation of mean CBFV during category shift of the WCST resulted in significantly increased values after category shift (MCA: P<0.001; ACA: P<0.01) as compared with CBFV before the category shift. These findings showed a different CBFV pattern during the TOH task and WCST than during the visuomotor test. In conclusion, TCD was able to assess CBFV in prefrontal functions, using a high resolution in time.     

颈动脉支架置入术对脑梗死患者脑血流动力学变化的随访观察及与临床预后的相关性分析

目的 随访观察颈动脉狭窄脑梗死患者支架置入术后的颅内血流动力学及脑血管反应性(cerebral vascular reactivity,CVR)的变化,比较介入治疗对颈动脉狭窄患者临床预后的影响。方法 选取本院收治的103例颈动脉狭窄的脑梗死患者,根据患者及家属的治疗意愿分为手术组50例和药物组53例; 手术组均接受颈动脉支架置入术(carotid artery stenting,CAS)及药物的治疗,药物组仅接受药物治疗,记录2组的NIHSS评分变化、脑卒中和死亡事件; 所有手术患者均在术前、术后3 d、1、3、6、12个月进行CDFI和TCD检查,测量颈动脉狭窄局部管径、狭窄段收缩期峰值流速(peak systolic velocity,PSV)、阻力指数(resistance index,RI)及同侧大脑中动脉(MCA)的PSV、搏动指数(pulsatilityt index,PI)及CVR,比较手术前后的血流动力学变化。结果 2组NIHSS评分变化均呈下降趋势(P<0.05),术后3、6、12个月手术组NIHSS评分明显低于药物组(P<0.05); 术后颈动脉原狭窄处内径明显增宽,PSV及RI低于术前,患侧大脑中动脉PSV、PI及CVR 高于术前(P均<0.05); 手术组手术前后的CVR与美国国立卫生研究院卒中量表评分呈负相关(r=-0.84,-0.75,-0.66,-0.78,-0.61,P<0.05)。结论 CAS治疗后颈动脉狭窄患者颈部血管结构及血流动力学明显改善,可有效改善脑梗死患者的中远期预后,且术后CVR的改变可用于预测CAS治疗后的中远期疗效。     

Source of cerebral microembolic signals in occlusion of the internal carotid artery

Background and purpose: There are several possible sources of cerebral embolic ischaemia distal to an occlusion of the internal carotid artery (ICA). Our aim was to identify the source of microembolic signals in the ipsilateral middle cerebral artery (MCA) by taking simultaneous bitemporal transcranial Doppler ultrasound recordings of the ipsilateral MCA and the contralateral ACA to find the route of potential microembolic material to MCA. Subjects and methods: The study group consisted of 38 patients with an occlusion of the ICA. With extracranial duplex sonography (ACUSON 128 XP; 7 MHz), performed by an experienced sonographer, the echo intensity and echo structure of the occluded ICA in the extracranial part (proximal) were classified as homogeneous or inhomogeneous. In addition, affected segments of the ipsilateral and contralateral carotid artery with arteriosclerotic vessel walls were compared. Microembolic signals were recorded with transcranial Doppler (TCD) monitoring. The microemboli counts in the MCA and ACA were added to the sum scores. Results: The number of affected segments of the carotid artery on the ipsilateral (the bifurcation, the external or common carotid artery) and contralateral side of occluded ICA were equally distributed. In ipsilateral MCA 3.1, 7.1 microemboli (average mean, SD) with a range of between 0 and 34 were counted, in the contralateral ACA 0.3, 0.6 (range of between 0 and 2). Regression analysis confirmed the non-predictability of the microemboli variance on the ipsilateral side of the occlusion from the variance on the contralateral side (multiple r: 0.024). We found no significant correlation between the echo intensity or echo structure of the occluded artery and an increased rate of microemboli in the ipsilateral MCA. Conclusions: Our results indicate a predominantly ipsilateral source for cerebral microemboli in ICA occlusion. The rate of cerebral microembolic signals was not influenced by the echo structure and echo intensity of the occluded ICA. Received: 24 May 1996 Received in revised form: 20 January 1997 Accepted: 31 January 1997     

Intracranial Hemodynamic Changes During Adult Moyamoya Disease Progression

Background and purpose

This study evaluated the changes in blood flow velocity in the anterior and posterior intracranial circulations according to the progression of moyamoya disease in adult patients.

Methods

We evaluated Suzuki''s angiographic stage and mean blood flow velocity (MBFV) changes in intracranial vessels from both sides in 19 adult moyamoya patients. We then analyzed the linearity of MBFV changes from early to late moyamoya stages in each intracranial vessel using piecewise linear regression models.

Results

The MBFV in the middle cerebral artery, terminal internal carotid artery, and anterior cerebral artery increased non linearly until stage III, and then decreased progressively up to stage VI. The ophthalmic artery also showed nonlinear velocity changes, with an increase in MBFV up to stage IV, followed by a decrease in MBFV up to stage VI. The MBFV of the basilar artery increased linearly from a normal velocity at an early moyamoya stage to a stenotic velocity at a late stage. There was no statistically significant regression model for the relationship between the MBFV in the posterior cerebral artery and moyamoya stage.

Conclusions

The nonlinear and/or linear MBFV changes associated with variable intracranial vessels might be useful in initial and follow-up evaluations of different stages of moyamoya disease.     

Helicobacter pylori and the risk of dementia: A population-based study

Introduction

Helicobacter pylori infection might increase risk of dementia, but available evidence is inconsistent, and longitudinal studies are sparse. We investigated the association between H. pylori serology and dementia risk in a population-based cohort.

The structure of wandering in dementia

‘Wandering’ is one of the most troublesome of behavioural problems in dementia. The term ‘wandering’ covers many different types of behaviour. We examined the hypothesis that the different types of wandering behaviour seen in dementia from a scale using data collected on 83 elderly subjects suffering from either Alzheimer's disease or multiinfarct dementia. We reject the scaling hypothesis. Our data suggest that there are three main categories of wandering behaviour, and that one of these categories is usefully divided into four subcategories.     

Primary degenerative dementia of the Alzheimer type in twins: Initial findings from the Maudsley Hospital Twin Register

In detailed published accounts to date of 40 twin pairs one or both of whom were said to have Alzheimer's disease (AD), 16 of 35 monozygotic (MZ) pairs were described as concordant for the disease and the remaining 19 pairs as discordant, while of the five pairs of dizygotic (DZ) twins two pairs were designated as concordant. However, these data have emerged almost exclusively from selective case reports and volunteer samples, resulting in an over-representation of MZ twins that complicates the overall interpretation of the data. In an effort to reduce such ascertainment bias, we screened for diagnoses consistent with AD in the Maudsley Hospital Twin Register, which consists of twins registered at the Bethlem Royal and the Maudsley Hospitals (London, UK) since 1948. Seven twins were identified who met criteria for primary degenerative dementia of the Alzheimer type. Available details of their affected status as well as of the status of their co-twins are presented and discussed.