Small vessel versus large vessel vascular dementia

Objective

The aim of this study was a cross-sectional comparison of clinical and MRI characteristics and risk factor profiles between patients with small vessel disease (lacunae and white matter hyperintensities) and large vessel disease (large territorial or strategical infarcts) in a large cohort of VaD patients.

Methods

Patients with VaD (NINDS-AIREN) were included in a large multicenter treatment trial (the VantagE study). All patients were examined by a neurologist and interviewed about their medical history. Based on MRI, patients were classified as having large vessel VaD, small vessel VaD, or a combination. Other MRI characteristics included white matter hyperintensities (WMH), medial temporal lobe atrophy (MTA) and general cortical atrophy.

Results

Of the 706 patients, 522 (74 %) had small vessel disease, 126 (18 %) had large vessel disease and 58 (8 %) had both. Patients with small vessel disease were older and less educated, and showed more cortical and medial temporal lobe atrophy than patients with large vessel disease. The most prevalent vascular risk factors (hypertension, diabetes and smoking) were equally distributed between the different types of VaD. However, patients with large vessel disease had more hypercholesterolemia and cardiac risk factors compared to patients with small vessel disease.

Conclusion

Cerebrovascular disease underlying VaD consists in the majority of small vessel disease and in about one fifth of large vessel disease. This study demonstrates heterogeneity between these two groups with regard to risk factor profile and atrophy scores on MRI.

     

Small vessel versus large vessel vascular dementia

Objective   

The aim of this study was a cross-sectional comparison of clinical and MRI characteristics and risk factor profiles between patients with small vessel disease (lacunae and white matter hyperintensities) and large vessel disease (large territorial or strategical infarcts) in a large cohort of VaD patients.     

Small vessel disease: neuropathology

Diseases of small cerebral blood vessels are heterogeneous in etiology and manifestations. Lipohyalinosis, venous collagenosis, amyloid angiopathy, and CADASIL affect different populations of blood vessels. Large and small hemorrhages, lacunae, cortical microinfarcts, and leukoaraiosis are the most important consequences of the small vessel angiopathies. Altered permeability as well as ischemia may be involved in the pathogenesis of the latter.     

Mixed dementia: Alzheimer's and cerebrovascular disease

"Mixed dementia" is traditionally defined as Alzheimer's disease with cerebrovascular disease (CVD). Because the risks of both neurodegenerative dementias and cerebrovascular disease increase with age, the mixed dementias are likely the most common. In practice, patients with mixed dementia are diagnosed by one of two routes: Either they have evidence of a neurodegenerative dementia and CVD at the outset, or, they have a classical neurodegenerative presentation but are found to have ischemic lesions by neuroimaging. These facts have implications for the development of evidence-based diagnostic criteria.     

Pathogenesis of Alzheimer's disease and dementia

The pathogenesis of Alzheimer's disease is far from clear since it is still undetermined whether and how extracellular beta-protein and cytoskeletal degeneration of neurons, which are colocalized in the association neocortex of Alzheimer patients, are related to one another. By using beta-protein and other derivatives of the precursor protein, efforts to cause cell lesions comparable to neurofibrillary degeneration have been fruitless. However, the view that the amyloid issued from the polymerisation of beta-protein is neurotoxic, remains the most attractive. To fully explore this hypothesis, attention should be paid to neurons that participate in neocortical circuits and to factors that may influence their vulnerability, whether selective or not, to beta-protein and associated proteins.     

Frontotemporal dementia to Alzheimer's disease

Behavioral manifestations may dominate the clinical picture of the frontal variant of frontotemporal dementia (fv-FTD) for a long time before the appearance of true cognitive deficits. On the other hand, a deficit in the episodic memory domain represents the main manifestation of Alzheimer's disease (AD). Many behavioral disorders have been described in the clinical course of both FTD and AD; however, apathy and personality changes characterize frontal dementias, while depression dominates in AD, at least in the earlier stages. Depending on the distribution of neural damage, different patterns of noncognitive manifestations may be expected in different subtypes of FTD. Recent research on the social cognition deficit in FTD has offered new insights into the relationship between cognition and behavior, suggesting that some aspects of the behavioral changes in dementia may be generated by impairment in this domain.     

Vascular dementia: atherosclerosis, cognition and Alzheimer's disease

Both Alzheimer's disease type pathology (neuritic plaques and neurofibrillary tangles) and evidence of atherosclerosis and infarcts are common in autopsy specimens from the brains of patients enrolled in longitudinal prospective cohorts; the relative contribution of each of these to overall cognitive function is unclear. In addition whether each of these two forms of brain pathology can accelerate the appearance of the other is also unclear. In this paper we examine the relationship among Alzheimer's brain pathology, cerebral infarcts and cerebral atherosclerosis. We conclude that each is an independent predictor of dementia. Moreover we do not find that atherosclerosis increases Alzheimer's type brain pathology or vice versa.     

脑小血管病与卒中后抑郁

卒中后抑郁(PSD)作为脑卒中后常见的并发症,对卒中的预后十分不利,因此对其发病机制的研究越来越受到人们的重视.既往影像学研究主要集中在PSD与急性卒中病灶的关系,结论不完全一致.近年来人们发现脑小血管病(SVD)与缺血性卒中密切相关,且很多研究表明SVD为血管性抑郁的重要的影像学表现和诊断标准.但其在PSD发病机制中的作用还不明确.本文主要通过介绍SVD的相关知识及其在PSD发病中的作用,来探讨SVD与PSD的关系.     

Cholesterol and pathological processes in Alzheimer's disease

Fundamental questions on the pathogenesis of Alzheimer's disease (AD) are how nontoxic, soluble amyloid beta-protein (A beta) is converted to its toxic, aggregated form and how functional tau is hyperphosphorylated to form neurofibrillary tangles. Growing evidence from recent biochemical and cell biological studies suggests that altered cholesterol metabolism in neurons may underlie such pathological processes. The possibility that cholesterol is a risk factor in the development of AD has also been supported by recent epidemiological studies. Based on this line of evidence, it is noteworthy to examine the potency of cholesterol-lowering medicine and/or diet in suppressing the development or the progression of AD.     

Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia

OBJECTIVES: The study aimed to increase understanding of behavioural changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). METHODS: A semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD patients. RESULTS: Behavioural changes that strongly discriminated FTD from AD and to a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies, loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of patients using regression analysis. CONCLUSIONS: Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion.     

Cytokines in Alzheimer's disease and vascular dementia

The levels of interleukin 1beta, interleukin 6, and interleukin 10 were elevated in the serum of patients with dementia. No statistically significant correlation was recorded in the interleukin levels among patients with Alzheimer's disease and vascular dementia. Also, no significant correlation was observed in the interleukin levels in the serum and the severity of dementia. However, a significant correlation was found between IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels and age. The levels of IL-1beta and IL-6 were positively correlated with hypertension, and IL-2 levels were negatively correlated. No correlation was found between depressive symptoms and levels of cytokines in the serum.     

Delusions in Alzheimer's disease and multi-infarct dementia

Neuropsychiatric symptoms such as delusions and misidentifications have been reported in dementia ranging from 10% to 73% in Alzheimer's disease (AD) patients and up to 40% in multi-infarct dementia (MID) patients. The aim of this study was to investigate in 61 AD and 31 MID patients both the frequency and the content of delusions during the course of illness and to evaluate the relationship between these and both functional and mental decline. The results indicated that delusion experiences had occurred in 45% of AD patients and in 38% of MID patients, occurring most frequently during the first year of illness. Patients who experienced psychiatric symptoms showed higher mini mental state examination scores and were less impaired in functional disability measures. With regard to the content, no significant differences were observed between AD and MID patients; 53% of psychotic symptoms were found to be paranoid delusions while 47% were misidentification delusions.     

Neuritic pathology and dementia in Alzheimer's disease

Previous studies of Alzheimer's disease (AD) have correlated the severity of dementia with either the number of senile plaques or neurofibrillary tangles. We used antibodies raised against amyloid beta/A4 protein of senile plaque cores and tau protein as well as thioflavine S and the Campbell-Switzer modification of the Hicks silver method to examine the hippocampal formation and five neocortical regions from 22 nondemented elderly control subjects and 34 demented patients with cerebral senile plaques and neurofibrillary tangles, without complicating disease processes. Ten control subjects (46%) had no beta/A4 protein deposition. Twelve control subjects (54%) had widespread beta/A4 protein deposition but no neocortical neuritic pathology. Of the 34 patients with AD-type changes, 27 (79%) had widespread senile plaques and neurofibrillary tangles, while 7 (21%) had neocortical senile plaques with few neurofibrillary tangles. All demented patients had widespread beta/A4 protein deposition and neocortical tau-immunoreactive, Hicks silver-positive dystrophic neurites. The neurites were found both free in the neuropil as well as surrounding senile plaques. Quantitative analysis showed that dystrophic neurites were significantly increased in patients with AD compared with control subjects and the number of dystrophic neurites and neurofibrillary tangles correlated with the clinical severity of dementia. Widespread cerebral beta/A4 protein deposition may be necessary but by itself is insufficient for the development of dementia in AD.     

Early Alzheimer's disease. Diagnostic considerations

An 82-year-old cognitively healthy man was assessed longitudinally until very mild senile dementia of the Alzheimer type was diagnosed by clinical research criteria and documented by psychometric testing at age 85 years. Four months after diagnosis, Alzheimer's disease was confirmed neuropathologically. The diagnostic difficulties involved in distinguishing early senile dementia of the Alzheimer type-Alzheimer's disease from normal aging are examined and clinical and pathologic features useful for their discrimination are discussed.     

First symptoms--frontotemporal dementia versus Alzheimer's disease

Frontotemporal dementia (FTD) is often misdiagnosed as Alzheimer's disease (AD). We hypothesized that the first symptoms associated with FTD would be different from those seen in AD and that the first symptoms in FTD would reflect loss of function in the frontal region with the greatest degree of degeneration. The objective of the study was to compare the earliest symptoms in patients with FTD and AD, and to delineate the symptoms that were associated with right, left or bilateral frontotemporal degeneration in FTD. The first symptoms in 52 FTD and 101 AD patients were determined in retrospect. Based on functional imaging studies, the FTD patients were divided into those with predominantly bilateral (n = 15), left-sided (n = 19) and right-sided (n = 18) patterns of atrophy. The results showed that disinhibition, social awkwardness, passivity and loss of executive function were more common in FTD, while memory loss was more common in AD. Disinhibition was greatest in the asymmetric right-sided group, language dysfunction was commonest in the asymmetric left-sided group and loss of executive function was most frequent in the bilateral group. In summary, different first symptoms appeared in FTD and AD, which may help distinguish between the diseases. The anatomic site for FTD largely determined the kind of first symptoms.