Is dementia a disease?

BACKGROUND: It is customary for many neurologists to think that dementia is a disease. This view is based on the following reasons: (1) a brain disease is the cause of cognitive impairment; (2) therefore, such cognitive impairment is substituted for the disease, becoming dementia, which is then also regarded as a mental disease. OBJECTIVE: In this brief article, I take exception to such a view, contrary to the common belief in the medical field, on the ground that senile plaques and/or neurofibrillary tangles or any other factors cause neuronal apoptosis but they do not cause dementia directly. METHODS: Literature on dementia and aphasia are critically and briefly reviewed to get the historical perspective that it is the progressive neuronal losses, losing brain functions as a result, that cause dementia; that is, brain diseases cause neuronal losses which then result in the decrease of brain functions, thereby leading to dementia. RESULTS: There is no direct cause-effect relationship between brain disease, be it caused by vascular factors or not, and dementia which is the consequence or sequela of neuronal losses. CONCLUSIONS: It is concluded that dementia is not a disease and yet it occurs not only in Parkinson's disease, Alzheimer's disease (AD), Huntington's disease and Pick's disease, but also in any other neurodegenerative disease, e.g., spinocerebellar ataxia, or vascular disease, e.g., Binswanger's disease, as part of the process of aging; in fact, AD is now regarded by some as a vascular disorder with neurodegenerative consequence, rather than a neurodegenerative disorder with vascular consequence. But vascular disorder is misleading if AD includes both neurofibrillary tangles and senile plaques; on the other hand, AD cannot be a vascular disorder if it includes only neurofibrillary tangles, as it should. Dementia, in this context, is re-defined as the differential manifestation of deteriorating brain functions over time as a part of aging due to cell deaths in the brain caused by any neurodegenerative disease. Its prominent symptoms are language disorders which must be distinguished from aphasias. It is also suggested that in fairness to Fischer, senile plaques be designated as Fischer's disease separate from neurofibrillary tangles for which AD was originally named as an eponym.     

Dementia secondary to metabolic and nutritional abnormalities

It is clear that dementia may result from nutritional and metabolic causes. Prior to labeling the demented person as having Alzheimer's disease or multi-infarct dementia, a thorough physical, historic, and laboratory evaluation is essential. Not only must other causes for the dementia be ruled out, but co-existing abnormalities that may confuse therapeutic intervention must be considered. Elderly persons notoriously under-report symptoms, in this case further complicated by the dementia. In addition, normal age-related changes, age-prevalent illness, and the atypical way in which diseases often present late in life may make the situation more confusing. Being aware of the wide variety of causes of dementia, however, will improve diagnostic abilities.     

尿酸对认知功能的影响

阿尔茨海默病和帕金森病是老年人常见的神经退行性疾病。认知功能障碍是阿尔茨海默病的主要临床表现,帕金森病在发展过程中,尤其到疾病晚期,可合并有痴呆表现,称帕金森病痴呆。不同的调查研究显示,帕金森病患者中有17％～57％会伴发认知功能障碍。研究影响认知功能的相关因素对于防治阿尔茨海默病,提高帕金森病患者的生活质量具有重要的意义。近年来发现,血尿酸水平与认知功能密切相关。     

Management for motor and non-motor complications in late Parkinson's disease

The prevalence of neurodegenerative diseases such as Parkinson's disease (PD) increases with age. In an aging population, an understanding of the management of late complications of PD is becoming ever more important. Drug treatment for Parkinson's disease is largely symptomatic and relies primarily on levodopa (L-dopa) and adjuvant therapies including dopamine agonists and catechol-O-methyltransferase (COMT) inhibitors. Rehabilitation and allied health input also constitutes a core part of successful management. Most subjects who are symptomatic for more than 5 years are prone to late complications of PD. Some of these are related to the treatment, such as motor fluctuations, including the "on-off" phenomenon and levodopa-related peak dose dyskinesia. Others, such as postural hypotension, falls, psychosis, and dementia, although well-recognized problems in the elderly, often require different treatment strategies if occurring in the context of PD. The practical evidence-based management of motor and non-motor complications in late PD is discussed.     

Our dementia challenge: arise palliative care

While many of the maladies of the 20th century are steadily coming under control, the march of neurodegenerative disorders continues largely unchecked. Dementias are an exemplar of such disorders; their incidence and prevalence continue to rise, in large part due to a steadily ageing population worldwide. They represent a group of chronic, progressive and, ultimately, fatal neurodegenerative diseases. Dementia has remained therapeutically recalcitrant. It is not a single disease, and because of that, we cannot expect a single panacea. While primary prevention rightly gains prominence, those with established disease currently require a shift in focus from curative intent towards improved quality of life. Enter palliative care. The sheer number and complexity of needs of patients with dementia, from the physical to the psychosocial and spiritual, necessitates the engagement of a wide range of medical disciplines, nursing and allied health professionals. One of those disciplines, as highlighted in the recent Australian Royal Commission into Aged Care Quality and Safety, is palliative care. This paper shall expand upon that role in the overall context of care for those with dementia.     

Gallyas-Braak银染法在神经系统变性疾病中的应用

目的 评估Gallyas-Braak银染色方法在几种神经系统变性疾病病理诊断中的作用和价值。方法 采用修订Gallyas-Braak染色法,对经临床和常规病理方法诊断的22例神经系统变性病的脑和脊髓标本进行了回顾性研究。结果 Gallyas-Braak银染色可良好显示Alzheimer病（AD）,其他变性病痴呆,正常老年人的海马及额、颞叶皮层神经原纤维缠结,且较Bodian染色清楚。在4例有痴呆症状和明显锥体外体征患者的中脑,基底节观察到大量神经元球形团样缠结,同时在运动皮层,基底节,中脑观察到星形细胞丛状缠结,其中2例符合进行性核上性麻痹的病理诊断标准,另2例观察到运动皮层和基底节区星形细胞斑,加之皮层神经元气球样变,符合皮质基底节变性的病理特征。3例多系统萎缩的脑和脊髓白质显示广泛分布少突胶质细胞包涵体。1例AD病的颞叶和海马皮质2－3层神经毡内显示嗜银颗粒,而Bodian染色未观察到这些病理改变。结论 Gallyas-Braak染色除显示神经原纤维缠结外,还能较好显示胶质细胞变性和神经毡异常结构,因此对进行性核上性麻痹,皮质基底节变性,多系统萎缩,嗜银颗粒病的病理诊断有重要价值。     

Neurodegenerative diseases and blood pressure variability: A comprehensive review from HOPE Asia

Asia has an enormous number of older people and is the primary contributor to the rise in neurodegenerative diseases such as Alzheimer''s and Parkinson''s disease. The therapy of many neurodegenerative diseases has not yet progressed to the point where it is possible to alter the course of the disease. Mid‐life hypertension is an important predictor of later‐life cognitive impairment and brain neurodegenerative conditions. These findings highlight the pivotal role of preventing and managing hypertension as a risk factor for neurodegenerative disease. Autonomic dysfunction, neuropsychiatric and sleep disturbances can arise in neurodegenerative diseases, resulting in blood pressure variability (BPV). The BPV itself can worsen the progression of the disease. In older people with neurodegenerative disease and hypertension, it is critical to consider 24‐h blood pressure monitoring and personalized blood pressure therapy.     

Doing dementia better: anthropological insights

Dementia, or neurodegenerative disease, is a disease category, and yet it is widely described in popular and professional media as a horror story. Patients with dementia and their families frequently report that they are less than pleased with their clinical encounters. This article reveals the deleterious impact that cultural assumptions about dementia have on the care provided, and, through an exploration of anthropological theories of personhood, suggests strategies for seeking improved quality of life through personhood-centered care.     

Parkinson's Disease and Parkinsonism

Parkinson's disease is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurologic ailment. Male sex and advancing age are independent risk factors and, as the population ages, is taking an increasing toll on productivity and medical resources. There are a number of other extrapyramidal conditions that can make the diagnosis challenging. Unlike other neurodegenerative diseases, idiopathic Parkinson's disease has effective treatments that mitigate symptoms. Medications can improve day-to-day function and, in cases where medication does not give a sustained benefit or has significant side effects, treatments like deep brain stimulation result in improved quality of life.     

Stem cell therapy extends incubation and survival time in prion-infected mice in a time window-dependant manner

Prion diseases, which are mostly represented in humans by Creutzfeldt-Jakob disease, are transmissible neurodegenerative disorders characterized by vacuolization and neuronal loss, as well as by the accumulation of an abnormal form of the prion protein. These disorders have yet no effective treatment, and drugs that block prion replication in vitro do not significantly slow down the progression of the disease when used in vivo at late stages. Cell therapy that has been already tested in other neurodegenerative disorders therefore represents an interesting alternative approach. In this study, we showed for the first time in prion diseases that intracerebral transplantation of fetal neural stem cells significantly extended both incubation and survival time. This result was dependant on the time window chosen for the engraftment and was obtained with both genetically modified and wild-type stem cells, therefore forging a path toward efficient stem cell therapy for human prion diseases.     

Neuropathology of Alzheimer's disease and other dementias

Clinical differentiation of neurodegenerative diseases that produce dementia is imprecise. Neuropathology offers the only way to make a definite diagnosis. The CNS autopsy is also important for clinical quality control and for providing tissue that furthers research into these disabling disorders. This brief article summarizes the major neuropathologic features of largely sporadic disorders that present with late-life dementia. The common causes of dementia discussed are Alzheimer's disease, Lewy body disease, and vascular dementia; less common disorders described are dementia lacking distinctive histopathology, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, and Creutzfeldt-Jakob disease.     

Dementia

Dementia is any decline in cognition that is significant enough to interfere with independent, daily functioning. Dementia is best characterized as a syndrome rather than as one particular disease. The causes of dementia are myriad and include primary neurologic, neuropsychiatric, and medical conditions. It is common for multiple diseases to contribute to any one patient's dementia syndrome. Neurodegenerative dementias, like Alzheimer disease and dementia with Lewy bodies, are most common in the elderly, while traumatic brain injury and brain tumors are common causes in younger adults. While the recent decade has seen significant advancements in molecular neuroimaging, in understanding clinico-pathologic correlation, and in the development of novel biomarkers, clinicians still await disease-modifying therapies for neurodegenerative dementias. Until then, clinicians from varied disciplines and medical specialties are well poised to alleviate suffering, aggressively treat contributing conditions, employ medications to improve cognitive, neuropsychiatric, and motor symptoms, promote evidence-based brain-healthy behaviors, and improve overall quality of life for patients and families.     

血管性认知障碍发病机制的研究进展

随着世界范围内人口老龄化的加剧,高血压、糖尿病、脑卒中等发病率的急剧增加,痴呆、帕金森病等神经退行性疾病的患病率也明显增高,血管性认知障碍（VCI）得到越来越多的关注,成为近十余年来的研究热点。VCI是一种具有潜在可预防性的临床综合征,早发现、早诊断、早治疗可在一定程度上延缓病情的进展。但VCI的病因、发病机制、诊断标准等问题仍有较大争议。     

Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease

Increasing evidence suggests an important role of mitochondrial dysfunction in the pathogenesis of many common age-related neurodegenerative diseases, including Alzheimer's disease (AD). AD is the most common neurodegenerative disorder characterized by dementia, memory loss, neuronal apoptosis and eventually death of the affected individuals. AD is characterized by two pathologic hallmark lesions that consist of extracellular plaques of amyloid-beta peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated microtubular protein tau. Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein and tau alterations in this type of dementia remains controversial.     

Higher-level hand motor function in aging and (preclinical) dementia: its relationship with (instrumental) activities of daily life--a mini-review

A causal relationship between physical activity such as walking and cognitive functions - particularly executive functions and memory - has been observed in elderly people with and without dementia. Executive functions play an important role in the (instrumental) activities of daily life [(I)ADL]. However, a close relationship has also been found between motor activity of the upper limb, particularly the hand, and (I)ADL. Indeed, in aging, a decline in hand motor function is related to a decrease in (I)ADL, an increase in functional dependency, admission to a nursing home, and even mortality. This review begins by addressing clinical studies on the effect of age on higher-level hand motor activity. It then discusses higher-level hand motor function in age-related neurodegenerative diseases such as mild cognitive impairment, Alzheimer's disease and vascular dementia. It concludes by discussing the contribution of higher-level hand motor function assessment to the diagnosis of the various subtypes of (preclinical) dementia and by addressing the clinical relevance of studying higher-level hand motor function, procedural learning, and (I)ADL in aging and (preclinical) dementia.     

脐血干细胞移植治疗血管性痴呆的可能性

血管性痴呆足常见的痴呆类型之一,其发生与脑血管病密切相关.脐血中含有丰富的可向神经细胞方向分化的干细胞.干细胞移植治疗缺血性脑血管病和神经系统变性疾病的研究已取得了一些成果,脐血干细胞也有可能用于血管性痴呆的治疗.     

Neuroimaging in the Clinical Diagnosis of Dementia: Observations from a Memory Disorders Clinic

OBJECTIVES: To determine how often neuroimaging confirms, clarifies, or contradicts initial diagnoses of late‐life cognitive disorders. DESIGN: Retrospective case review. SETTING: Outpatient clinic specializing in memory disorders. PARTICIPANTS: One hundred ninety‐three consecutively referred cognitively impaired patients. MEASUREMENTS: Diagnoses using research criteria were developed for each patient at the first visit and ranged from cognitive impairment without dementia to dementias of single, complex, or indeterminate etiology. Structural (noncontrast magnetic resonance imaging) and perfusion (technetium‐99m ethyl cysteine dimer single photon emission computed tomography) images were categorized together as normal, suggestive of specific diseases, or abnormal/not diagnostic. RESULTS: When a single neurodegenerative disease was suspected clinically (n=94), imaging confirmed the diagnosis in 50, contradicted the diagnosis in 32, and was abnormal/not diagnostic in 12. When more than one neurodegenerative etiology was clinically suspected (n=21), imaging assigned a single diagnosis in 13 and only cerebrovascular disease in one and was abnormal/not diagnostic in seven. In dementia not otherwise specified (NOS) (n=33), imaging suggested a specific etiology in 23 and was abnormal/not diagnostic in 10. Abnormal/not diagnostic images were more common in cognitive disorder NOS (n=25, 68%) than in other clinical groups (22%, chi‐square=22.8 P<.001). Neuroimaging indicators of cerebrovascular disease were common (60% prevalence) but not predicted by the presence of vascular risk factors alone. CONCLUSION: Overall, neuroimaging confirmed, clarified, or contradicted the initial clinical diagnosis in more than 80% of patients, whereas fewer than 20% had abnormal/not diagnostic patterns. Imaging suggested a complex dementia etiology in 21% of cases clinically thought to be caused by a single process, whereas 46% of complex clinical differential diagnoses appeared to reflect a single causal pattern. Further work is needed to determine whether refinement of clinical diagnoses using specialized neuroimaging improves clinical decision‐making and patient outcomes.     

The cholinergic deficiency syndrome and its therapeutic implications

Cholinesterase inhibitors are licensed for treatment of dementia in Alzheimer's disease. However, the effects of these drugs on the cognitive symptoms of dementia are very small. We suggest that symptoms like impairment of attention and concentration, anxiety, restlessness and hallucinations, delineate a specific central cholinergic deficiency syndrome (CDS), that may be a much better target for such treatment. Changes in the quantitative electroencephalogram, muscarinic subtype radioimaging and serum anticholinergic activity may potentially help to diagnose the CDS. CDS is suggested to occur in various neurodegenerative diseases like Alzheimer's disease, Lewy body dementia and Parkinson's disease and to respond well to cholinesterase inhibitor therapy.     

Imaging cerebral atrophy: normal ageing to Alzheimer's disease

CONTEXT: With ageing populations, the prevalence of dementia, especially Alzheimer's disease, is set to soar. Alzheimer's disease is associated with progressive cerebral atrophy, which can be seen on MRI with high resolution. Longitudinal MRI could track disease progression and detect neurodegenerative diseases earlier to allow prompt and specific treatment. Such use of MRI requires accurate understanding of how brain changes in normal ageing differ from those in dementia. STARTING POINT: Recently, Henry Rusinek and colleagues, in a 6-year longitudinal MRI study of initially healthy elderly subjects, showed that an increased rate of atrophy in the medial temporal lobe predicted future cognitive decline with a specificity of 91% and sensitivity of 89% (Radiology 2003; 229: 691-96). WHERE NEXT? As understanding of neurodegenerative diseases increases, specific disease-modifying treatments might become available. Serial MRI could help to determine the efficacy of such treatments, which would be expected to slow the rate of atrophy towards that of normal ageing, and might also detect the onset of neurodegeneration. The amount and pattern of excess atrophy might help to predict the underlying pathological process, allowing specific therapies to be started. As the precision of imaging improves, the ability to distinguish healthy ageing from degenerative dementia should improve.     

Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies

Misfolded neuronal proteins have been identified in a number of neurodegenerative disorders and have been implicated in the pathogenesis of diseases that include Alzheimer's disease, Parkinson's disease, prion-based dementia, Huntington's disease (HD), and other polyglutamine diseases. Although underlying mechanisms remain the subject of ongoing research, it is clear that aberrant processing, protein degradation, and aggregate formation or spurious protein association of the abnormal neuronal proteins may be critical factors in disease progression. Recent work in these diseases has demonstrated in vitro that specific engineered antibody species, peptides, or other general agents may suppress the formation of aggregates. We have modified an approach with intracellularly expressed single-chain Fv (sFv) antibodies (intrabodies) that bind with unique HD protein epitopes. In cell and tissue culture models of HD, anti-N-terminal huntingtin intrabodies (C4 sFv) reduce aggregation and cellular toxicity. Here, we present the crucial experiment of intrabody-mediated in vivo suppression of neuropathology, using a Drosophila model of HD. In the presence of the C4 sFv intrabody, the proportion of HD flies surviving to adulthood increases from 23% to 100%, and the mean and maximum lifespan of adult HD flies is significantly prolonged. Neurodegeneration and formation of visible huntingtin aggregates are slowed. We conclude from this investigation that engineered intrabodies are a potential new class of therapeutic agents for the treatment of neurodegenerative diseases. They may also serve as tools for drug discovery and validation of sites on mutant neuronal proteins that could be exploited for rational drug design.