Mild Cognitive Impairment and Mild Dementia: A Clinical Perspective

Mild cognitive impairment and mild dementia are common problems in the elderly. Primary care physicians are the first point of contact for most patients with these disorders and should be familiar with their diagnosis, prognosis, and management. Both mild cognitive impairment and mild dementia are characterized by objective evidence of cognitive impairment. The main distinctions between mild cognitive impairment and mild dementia are that in the latter, more than one cognitive domain is invariably involved and substantial interference with daily life is evident. The diagnosis of mild cognitive impairment and mild dementia is based mainly on the history and cognitive examination. The prognosis for mild cognitive impairment and mild dementia is an important motivation for diagnosis because in both, there is a heightened risk for further cognitive decline. The etiology of mild cognitive impairment and mild dementia can often be established through the clinical examination, although imaging and other laboratory tests may also contribute. Although Alzheimer disease is the most common cause of both, cerebrovascular disease and Lewy body disease make important contributions. Pharmacological treatments are of modest value in mild dementia due to Alzheimer disease, and there are no approved pharmacological treatments for mild cognitive impairment of any etiology. Nonetheless, new-onset cognitive impairment is a worrisome symptom to patients and families that demands answers and advice. If a patient is having difficulties managing medications, finances, or transportation independently, diagnosis and intervention are necessary to ensure the health and safety of the patient.     

神经内科门诊痴呆的流行病学调查

目的 了解神经内科门诊55岁以上患者痴呆的就诊比例及各痴呆亚型的比例,探讨各痴呆亚型的临床特点;了解APOE基因与阿尔茨海默病的相关性.方法 选取2009年9月25日到2009年12月25日在四川省人民医院神经内科门诊就诊的患者14 286人为研究对象,分别用老年人认知功能减退知情者问卷（IQCODE）、简易精神状态量表（MMSE）、Hachinski缺血指数量表（HIS）、日常生活能力量表（ADL）、神经精神问卷（NPI）、Hamilton抑郁量表、自发的画钟测验（CDT）、临床痴呆评定量表（CDR）量表进行检测,诊断痴呆患者进行抽血检查APOE基因.结果 在所有就诊患者中阿尔茨海默病占1.99％;血管性痴呆占0.95％;混合性痴呆占0.47％;额颞叶痴呆占0.19％;其他类型痴呆占0.19％.在所有痴呆患者中阿尔茨海默病占52.5％,血管性痴呆占25％,混合性痴呆占12.5％,额颞叶痴呆占5％,其他类型痴呆占5％.阿尔茨海默病与混合性痴呆在即刻记忆、延迟记忆、长延迟再认的得分明显低于血管性痴呆;在定向力、判断力、计算力、日常生活能力方面的得分情况三者无差异;轻度阿尔茨海默病、混合性痴呆在Hamilton抑郁量表中的得分明显高于中重度阿尔茨海默病及血管性痴呆.中重度阿尔茨海默病及血管性痴呆在神经精神问卷中的得分明显高于轻度阿尔茨海默病及混合性痴呆.在自发的画钟测验方面,血管性痴呆得分要高于阿尔茨海默病及混合性痴呆.APOEε4等位基因与阿尔茨海默病密切相关.结论 阿尔茨海默病为主要的痴呆类型,其次为血管性痴呆、混合性痴呆、额颞叶痴呆及其他类型痴呆.阿尔茨海默病、血管性痴呆及混合性痴呆在认知功能损害方面存在差异.阿尔茨海默病与APOE4基因相关.     

Early diagnosis of dementia

Until recently, the most significant issue facing a family physician regarding the diagnosis and treatment of dementia was ruling out delirium and potentially treatable etiologies. However, as more treatment options become available, it will become increasingly important to diagnose dementia early. Dementia may be suspected if memory deficits are exhibited during the medical history and physical examination. Information from the patient's family members, friends and caregivers may also point to signs of dementia. Distinguishing among age-related cognitive decline, mild cognitive impairment and Alzheimer's disease may be difficult and requires evaluation of cognitive and functional status. Careful medical evaluation to exclude treatable causes of cognitive impairment is important. Patients with early dementia may benefit from formal neuropsychologic testing to aid in medical and social decision-making. Follow-up by the patient's family physician is appropriate in most patients. However, a subspecialist may be helpful in the diagnosis and management of patients with dementia with an unusual presentation or following an atypical course.     

Neuroimaging in dementia: in vivo amyloid imaging

Dementia, a progressive cognitive decline, leads to a gradually increasing restriction of daily activities. Alzheimer's disease (AD) is the most common form of dementia. The pathological features of AD include plaques and tangles which are constituted by amyloid beta peptide (A beta) and tau protein. These amyloidogenic molecules have been mechanistically implicated in the pathogenesis of AD and related neurodegenerative dementias. The key strategy for establishment of diagnostic and therapeutic approaches to AD is sensitive and specific detection of the incipient neuropathology characteristics of AD, combined with emerging treatments that counteract molecular processes in AD pathogenesis. Recent advances in molecular imaging research have enabled visualization of brain amyloidosis. The rapid development of different compounds suitable for visualizing amyloid would permit pathology-specific diagnosis of AD at an asymptomatic stage in a noninvasive manner, and could also allow early immunotherapeutic intervention without causing an excessive neuroinflammatory response.     

Alzheimer disease and its management: a review

Alzheimer disease is a progressive degenerative disorder of the brain characterized by a slow, progressive decline in cognitive function and behavior. As the disease advances, persons with Alzheimer disease have tough time with daily usage of things like using the phone, cooking, handling money, or driving the car. The disease is more common in elder population. It is estimated that Alzheimer disease affects 15 million people worldwide and approximately 4 million Americans. The clinical features of Alzheimer disease overlaps with common signs of aging, and other types of dementia, hence the diagnosis remains difficult. The neuropathologic hallmarks of the disorder are amyloid-rich senile plaques, neurofibrillary tangles, and neuronal degeneration. Drugs approved for treating Alzheimer disease include acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonist. Caregivers not getting adequate information about Alzheimer disease may believe that nothing can be done to manage its symptoms. Understanding the extent of Alzheimer disease related knowledge can assist disease management that result in improved disease management and reduced care costs. This article attempts to focus on some of the important recent developments in understanding and management of Alzheimer disease.     

Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of a multicenter, double-blind trial

BACKGROUND: Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias. OBJECTIVE: This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia. METHODS: This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination. RESULTS: Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results. CONCLUSION: The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.     

Frontotemporal dementia]

BACKGROUND: Among the primary degenerative dementias, frontotemporal dementia (FTD, Pick's disease) is very important along with Alzheimer's disease. The estimated prevalence is 15:100,000 in the 45- to 64-year-old population; thus, it appears that the FTD as a cause for so-called presenile dementia is nearly as common as Alzheimer's disease. CASE REPORT: The case of a 52-year-old woman is described that presented with slowly progressive lack of concentration and disturbance of memory. Furthermore, the immediate family had noticed a change in her premorbid personality. Due to additional depressive symptoms, she was misdiagnosed with depressive pseudodementia first. CONCLUSION: Since the clinical presentation of FTD is variable and the correct classification has been uncertain for a long time, clinical diagnosis can be very difficult, so that the disease is often detected too late or remains completely misdiagnosed. On this basis, pathology, clinical aspects, diagnosis, and therapeutic options of FTD will be demonstrated according to current standards of knowledge.     

Update on Treatments for Cognitive Decline in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and a leading cause of dementia in the elderly. AD initially presents as mild cognitive impairment (MCI); later, as AD progresses, memory and cognition are destroyed, preventing the ability to carry out activities of daily living. The primary care provider may be the first to suspect MCI, and screening tests can help with diagnosis. Development of drugs for cognitive decline in AD has been slow; however new therapies are in the pipeline and discovery of biomarkers make early diagnosis and future treatment of AD hopeful.     

神经内科门诊患者可康复性痴呆的流行病学特征

背景:目前国内对可康复性痴呆的流行病学研究和报道较少。目的:研究可康复性痴呆的流行病学特点。设计:以诊断为依据的临床回顾性随访研究。地点和对象:1994-03/2003-04对陕西省纺织医院神经内科门诊患者254例进行追踪随访。干预:通过回顾,分析可康复性痴呆的流行病学特点。根据不同患者的情况采用不同的治疗措施。主要观察指标:临床症状和体征、认知能力和智能测试,多项实验室的检查,头颅CT扫描或磁共振成像。结果:在门诊254例患者中,符合DSM-Ⅳ痴呆的诊断标准115例,其中最多的是阿尔茨海默病69例(占60%)。对10例可康复性痴呆(占8.7%)的观察,脑积水(4例)和神经性梅毒(2例)是常见的病因。完全康复的有2例患者,部分康复的3例,2例未治,3例失去随访。结论:可康复性痴呆患者约占8.7%和文献报道的0～30%相一致,病因的研究对可康复痴呆治疗有重要意义。     

Treatment of Alzheimer disease

Alzheimer disease is the most common form of dementia, affecting more than one-third of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy.     

What is new in degenerative dementia disorders?

Alzheimer's disease and other degenerative disorders--dementia with Lewy bodies, frontotemporal dementia, etc.--causing about 90% of dementias in advanced age, are a major health problem of increasing practical, scientific, and socio-economic importance. Despite considerable progress in genetic, clinical and basic neurosciences, the aetiology and molecular mechanisms of these disorders are still unknown and their early diagnosis, due to lack of specific biomarkers, is still unsatisfactory. The epidemiology, risk factors, clinical and morphological diagnostic criteria, probable pathogenic factors, and molecular genetics of the major types of degenerative dementias are reviewed. Their management involves several pharmacologic, non-pharmacologic and psychosocial options. Modification of the disease by reducing known and presumable risk factors, cognitive enhancement with cholinomimetic drugs, and reduction of behavioural abnormalities with psychotropic drugs, together with informed community and private management are currently achievable goals that will serve to delay the progression of disease. In the future, these options will hopefully be replaced by more effective management strategies in order to improve the quality of life of both, patients and caregivers.     

Alzheimer's disease

Alzheimer's disease is a complex and fascinating entity, clinically and neurobiologically. Although originally described as a form of accelerated aging in an article that emphasized neuropathology, it is now considered a specific age-related disease entity, at whatever age it occurs. It is the most common cause of the dementia syndrome, probably the fourth most common cause of death in the United States and is likely to become more common as the population ages. The course is typically an insidious onset of cognitive and behavioral impairment progressing more or less steadily over years to profound disability. The classic pathologic changes are Alzheimer plaques, neurofibrillary tangles, and loss of subcortical cells, including particularly the cholinergic cells of the nucleus basalis complex. The functional disability can be correlated with the site and extent of brain damage, but why these cells deteriorate and die is not known. Diagnosis depends on identifying the dementia syndrome in a patient whose course is compatible with Alzheimer's disease and in whom no other factors adequate to explain the dementia are found. NIH consensus diagnostic criteria are now available. Care is symptomatic optimal care of intercurrent illness, and pharmacologic, behavioral, and social "splints" to maximize the function of the remaining brain. Specific treatments are still in the realm of research, and both clinical and basic research on this challenging disorder are active and accelerating.     

Clinical, diagnostic, genetic and management issues in dementia with Lewy bodies

DLB (dementia with Lewy bodies) is a syndrome associated with underlying LBD (Lewy body disease), with manifestations in the cognitive, neuropsychiatric, motor, sleep and autonomic domains. The variable symptomatology and complex array of neuronal involvement and neurotransmitter deficiencies make the diagnosis and management of patients with DLB challenging. The genetic underpinnings of DLB have only recently begun to unfold. In this review, the clinical features, diagnostic criteria, genetics and treatment issues relating to DLB will be discussed, in which a comprehensive approach to the diagnosis and management is emphasized.     

Vascular dementia subtypes,pathophysiology, genetics,neuroimaging, biomarkers,and treatment updates along with its association with Alzheimer's dementia and diabetes mellitus

Dementia is a chronic progressive cognitive decline illness that results in functional impairment. Vascular dementia (VaD), second only to Alzheimer's disease (AD), is one of the most prevalent forms of dementia in the elderly (aged over 65 years), with a varied presentation and unpredictable disease development caused by cerebrovascular or cardiovascular illness. To get a better understanding of the changes occurring in the brain and to drive therapy efforts, new biomarkers for early and precise diagnosis of AD and VaD are required. In this review, Firstly, we describe the subtypes of vascular dementia, their clinical features, pathogenesis, genetics implemented, and their associated neuroimaging and biomarkers, while describing extensively the recent biomarkers discovered in the literature. Secondly, we describe some of the well-documented and other less-defined risk factors and their association and pathophysiology in relation to vascular dementia. Finally, we follow recent updates in the management of vascular dementia along with its association and differentiation from Alzheimer's disease. The aim of this review is to gather the scattered updates and the most recent changes in blood, CSF, and neuroimaging biomarkers related to the multiple subtypes of vascular dementia along with its association with Alzheimer's dementia and diabetes mellitus.     

老年人轻度认知损害的发病率及向痴呆或阿尔茨海默病的转化率:基于人群的队列研究

背景:老年人轻度认知损害已成为目前阿尔茨海默病临床研究的新热点。目前国内有多少轻度认知损害对象发展为阿尔茨海默病还是一个未知数。目的:分析老年人轻度认知损害的发病率及向痴呆和阿尔茨海默病的转化率。设计:以诊断为依据的队列研究。单位:解放军白求恩国际和平医院干部病房二科。对象:为2001-08/2001-09对石家庄市26个部队干休所60岁及以上的离退休干部进行基线调查时诊断为轻度认知损害的216例患者和2302名认知正常受试者。方法:轻度认知损害的诊断参考美国精神障碍诊断与统计手册第4版轻度神经认知损害研究用诊断标准。痴呆的诊断采用美国精神病学会的精神障碍诊断和统计手册第四修订版(DSM-IV)标准。阿尔茨海默病采用美国神经病学、语言障碍和卒中-老年性痴呆和相关疾病学会标准。对216例轻度认知损害患者和2302名认知正常受试者进行为期3年的队列研究。主要观察指标:认知正常受试者轻度认知损害的平均年发病率、认知正常受试者和轻度认知损害患者阿尔茨海默病的平均年发病率以及轻度认知损害患者与认知正常受试者比较转化为阿尔茨海默病的相对危险性(RR)和95%可信区间。结果:轻度认知损害组与认知正常组均每年随访1次,共随访3年。216例轻度认知损害患者死亡7例,实际随访209例,随访率96.8%。2302名认知正常者死亡36例,实际随访2266例,随访率98.4%。①认知正常的老年人轻度认知损害的平均年发病率为4.8%,痴呆和阿尔茨海默病的平均年发病率分别为1.3%和0.8%;②轻度认知损害患者痴呆和阿尔茨海默病的平均年发病率分别为8.1%和5.6%;男性和女性轻度认知损害患者痴呆和阿尔茨海默病的平均年发病率差别无显著性(P>0.05)。③随着文化程度的提高,轻度认知损害患者痴呆(趋势χ2=5.57,P=0.02)和阿尔茨海默病(趋势χ2=4.92,P=0.03)的发病率有降低的趋势;认知正常受试者痴呆(趋势χ2=23.1,P<0.001)和阿尔茨海默病(趋势χ2=18.0,P<0.001)的发病率亦有降低的趋势。④随着年龄的增长,轻度认知损害患者痴呆(趋势χ2=14.6,P<0.01)和阿尔茨海默病(趋势χ2=13.9,P<0.01)的平均年发病率有增高的趋势;认知正常受试者痴呆(趋势χ2=32.3,P<0.01)和阿尔茨海默病(趋势χ2=23.8,P<0.01)的平均年发病率亦有增高的趋势。⑤轻度认知损害转化为痴呆或阿尔茨海默病的相对危险性分别为认知正常者的6.4倍和7.4倍。结论:老年轻度认知损害患者转化为痴呆的危险性远远大于认知正常的老年人。应加强对老年轻度认知损害患者这一痴呆高危人群的监测。     

Cognitive and motor symptoms in dementia: focus on dementia with Lewy bodies

PURPOSE: To describe the clinical syndrome called dementia with Lewy bodies (DLB) and highlight its common and unique characteristics with respect to diagnosis and management. DATA SOURCES: Review of the scientific literature including psychiatric literature, reports of clinical trials, and clinical practice guidelines. CONCLUSIONS: DLB is a clinical and histopathologic disease, which is second only to Alzheimer's disease (AD) as a cause of dementia in older adults. The clinical syndrome of DLB includes cognitive and motor deterioration reminiscent of symptoms associated with AD and Parkinson's disease (PD) respectively. IMPLICATIONS FOR PRACTICE: The late life intersection of cognitive and motor symptoms can present significant challenges in the primary care setting. Recognizing key features of common neurodegenerative disorders is essential to accurately diagnosing and appropriately treating the growing population of older adults who suffer from AD, PD, and DLB.     

Biomarker of dementia: clinical and preclinical diagnosis

Recent advances in biomarker studies on dementia are summarized here. CSF Abeta40, Abeta42, total tau and phosphorylated tau are most sensitive biomarkers for diagnosis of Alzheimer's disease (AD) and prediction of onset of AD from mild cognitive impairment (MCI). Based on this progress, new diagnostic criteria for AD, MCI and preclinical AD were proposed by National Institute of Aging (NIA) and Alzheimer' s Association. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.     

Applause sign: screening utility for dementia and cognitive impairment

Objective: To examine the diagnostic utility of applause sign scores for the diagnosis of dementia and mild cognitive impairment. Methods: Consecutive unselected new outpatient referrals to a dedicated cognitive disorders clinic over a 12-month period were administered the clapping test. Criterion diagnosis was by usual clinic assessment using standard diagnostic criteria, blind to applause sign score. Results: Applause sign scores differed significantly (p < 0.001) between diagnostic groups (dementia, mild cognitive impairment, subjective memory complaint) and did not correlate with other cognitive screening instrument scores. Nearly three-quarters of those with an abnormal score had cognitive impairment. Applause sign score was specific but not sensitive for a diagnosis of cognitive impairment. Conclusion: The applause sign supports a diagnosis of dementia or cognitive impairment in high prevalence settings and may be useful in conjunction with other cognitive screening tests.