阿尔茨海默病患者神经精神症状与脑白质高信号的相关性分析

目的 分析阿尔茨海默病（AD）患者脑白质高信号（WMH）与神经精神症状（NPSs）的相关 性。方法 选取 2021 年 4 月至 2022 年 3 月在成都市第四人民医院记忆门诊就诊的 97 例 AD 患者为研究 对象。采用简易精神状态检查（MMSE）、日常生活活动能力量表（ADL）、神经精神科问卷（NPI）评估患者 的认知功能、日常生活活动能力和 NPSs。对患者的头部进行 3T MRI 扫描后,采用 UBO-Detctor 软件提 取患者各脑区 WMH 体积。采用偏相关分析 AD 患者各脑区 WMH 体积与 MMSE、ADL、NPI 评分的相关 性。结果 97 例 AD 患者的 MMSE 评分为 11.0（5.5,19.0）分,ADL 评分为 38.0（26.0,54.0）分,NPI 评分为 16.0（3.0,34.0）分。AD 患者的 MMSE 评分与全脑、脑室周围、左侧颞叶、右侧颞叶 WMH 体积呈负相关（r= -0.240、-0.239、-0.332、-0.208;P＜ 0.05）;ADL 评分与左侧颞叶、右侧颞叶 WMH 体积呈正相关（r=0.352、 0.257;P＜ 0.05）;NPI 评分与左侧颞叶 WMH 体积呈正相关（r=0.373,P＜ 0.05）。NPI 的 12 项症状中, AD 患者妄想与左侧枕叶 WMH 体积呈正相关（r=0.214,P＜ 0.05）;幻觉、激越 / 攻击性与左侧颞叶、顶叶 WMH 体积呈正相关（r=0.354、0.212、0.460、0.254;P＜ 0.05）;焦虑、情感高涨 / 欣快、睡眠 / 夜间行为、食 欲 / 进食障碍与左侧颞叶 WMH 体积呈正相关（r=0.222、0.422、0.295、0.222;P＜ 0.05）。结论 脑白质 的损伤程度与 AD 患者的认知功能、日常生活能力及 NPSs 存在相关性,不同脑区的白质损伤与不同的 NPSs 相关,预防脑白质的损伤或能改善 AD 患者的 NPSs。     

Anosognosia and neuropsychiatric symptoms and disorders in mild Alzheimer disease and mild cognitive impairment

Anosognosia is a multidimensional phenomenon that negatively affects course of illness. This study aimed to explore the association between anosognosia and neuropsychiatric phenomena in mild Alzheimer's disease (AD) and in mild cognitive impairment (MCI). The Anosognosia Questionnaire for Dementia to assess anosognosia, and the Neuropsychiatric Inventory to assess neuropsychiatric symptoms were administered to 209 patients (103 mild AD, 52 amnestic-MCI, and 54 amnestic multidomain-MCI). Categorical diagnoses of apathy, depression, and psychosis were made using specific criteria for dementia. With regard to continuous scores, in mild AD, we found positive correlation between symptoms of anosognosia and apathy, agitation and aberrant motor behaviors, while in MCI, we did not find significant association. At a categorical level, the diagnosis of anosognosia in mild AD was associated with the diagnosis of apathy. In mild AD, the frequent co-occurrence of frontally mediated behavioral disorders and anosognosia, particularly apathy, supports the hypothesis of a shared neuropsychogenic process due to the disruption of frontal brain networks.     

Persistence of and changes in neuropsychiatric symptoms in Alzheimer disease over 6 months: the LASER-AD study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD). It is important in terms of management to know their natural history and their effects on service use. The authors aimed to determine the persistence and change in severity of NPS over 6 months in participants with AD, and the relationship to initial severity, drug management, use of services, and cost of care. METHODS: NPS scores and data on cognition, psychotropic medication, service use, and costs of care were collected on 224 participants at baseline and on 198 at 6-month follow-up. RESULTS: Of 224 patients, 210 (93.8%) had NPS at baseline; 168 (75.0%) had at least one clinically significant symptom, 118 (80.4%) of whom had persistent significant symptoms at 6-month follow-up. There was no significant change in mean NPS score for any symptom over 6 months, but many individuals became better or worse; 61.2% of those with at least one significant baseline symptom in any domain improved. Those with persistent symptoms had more severe baseline symptoms. Deterioration in NPS was predicted by deterioration in MMSE. Those with at least one clinically significant symptom had higher care costs than those without. CONCLUSIONS: NPS were highly persistent overall, but many individuals became better or worse. Persistence was predicted by having more severe symptoms at baseline. Clinically significant levels of NPS were associated with greater costs of care. The relatively few associations found between specific psychiatric treatments and changes in NPS reflect both undertreatment and the complexity of symptoms.     

Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease

BACKGROUND: Serotonin has been linked to neuropsychiatric symptoms in Alzheimer disease, mainly agitation/aggression, depression, and psychosis. Neuropsychiatric symptoms have been associated with polymorphisms of the promoter region (5-HTTPR ) and intron 2 of the serotonin transporter gene (5-HTTVNTR) or the 5-HT2A and 5-HT2C receptor genes in some but not all studies. OBJECTIVE: To examine the association of the serotonin promoter, transporter, and receptor genes with neuropsychiatric symptoms in patients with Alzheimer disease. METHODS: The sample included 96 patients with Alzheimer disease from the outpatient clinic of the University of California Los Angeles Alzheimer's Disease Research Center, Los Angeles. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and blood samples were available for genetic analysis. Based on the literature, we hypothesized that the 5-HT2A and 5-HT2C receptor polymorphisms would be associated with agitation/aggression and psychosis and the 5-HTTPR or 5-HTTVNTR polymorphisms, with agitation/aggression or depression and anxiety. One-way analyses of variance were performed with age, ethnicity, sex, or education as covariates. RESULTS: The 102T genotype of the 5-HT2A receptor was significantly associated with delusions (P =.045) and agitation/aggression (P =.002). We did not replicate previous associations of the 5-HT2C receptor polymorphism with psychosis or of the 5-HTTPR polymorphism with agitation/aggression, psychosis, or depression. We did not find any associations with the 5-HTTVNTR polymorphism and agitation/aggression, depression, or anxiety. CONCLUSIONS: The 5-HT2A receptor polymorphism may contribute to the expression of psychosis and agitation/aggression in patients with Alzheimer disease. Absence of other positive associations may be due to the relatively small sample size and/or potentially small effect size of the polymorphisms and requires further study.     

Longitudinal evaluation of neuropsychiatric symptoms in Huntington's disease

A group of 111 patients with Huntington's disease (HD) underwent a minimum of three annual neuropsychiatric assessments, using the Problem Behaviors Assessment for Huntington's Disease (PBA-HD). Longitudinal prevalence of neuropsychiatric symptoms was notably higher than baseline prevalence, suggesting that previous studies may have underestimated the extent of this clinical problem. Moreover, apathy, irritability, and depression were each associated with distinct longitudinal profiles. Apathy progressed over time and across disease stages. Irritability also increased significantly, but only in early stages of HD. Depression did not increase significantly at any stage of disease. The neuropsychiatric syndrome of apathy appears to be intrinsic to the evolution and progression of HD.     

Neuropsychiatric symptoms and quality of life in Alzheimer disease.

OBJECTIVE: Authors examined the impact of neuropsychiatric symptoms in Alzheimer disease (AD) patients' and caregivers' quality of life (QOL) and assessed the relationship of caregiver distress to neuropsychiatric symptoms and caregiver QOL. METHODS: Sixty-two patients with probable or possible AD and their caregivers participated. Neuropsychiatric symptoms of patients were assessed with the Neuropsychiatric Inventory (NPI). QOL of both patients and caregivers was assessed using the QOL-Alzheimer's Disease (QOL-AD) scale. Each patient and caregiver completed patient QOL ratings; caregivers also completed caregiver QOL assessments. RESULTS: Caregiver QOL-AD was negatively correlated with agitation/aggression, anxiety, disinhibition, irritability/lability, and total NPI score. Patient QOL on both patient and caregiver ratings was negatively correlated with depression. Patient-reported QOL-AD ratings at different levels of cognitive functioning were not correlated with caregiver-reported ratings. The lack of relationship between patient and caregiver assessments of patient QOL was evident in both mildly and moderately affected patients. Caregiver QOL was negatively correlated with distress related to agitation/aggression, disinhibition, irritability/lability, and total NPI distress. CONCLUSION: Neuropsychiatric symptoms of AD patients adversely affect both patient and caregiver QOL. These results suggest that identifying and treating neuropsychiatric symptoms in AD may improve both patient and caregiver QOL.     

Pharmacologic options for the management of multiple sclerosis symptoms

Multiple sclerosis (MS) is a disease with a wide-ranging impact on physical functioning. Although pharmacotherapy plays an indispensable role in the management of MS symptoms, optimal disease management requires a multidisciplinary approach that combines medication, rehabilitation, and patient education. Successful control of symptoms is critical to quality of life for MS patients. Immunomodulating drugs provide a means of controlling the underlying disease process, but they are not a cure. This places responsibility on health care providers to control a patient's MS-related symptoms to limit disability and delay impairment in the activities of daily living. Owing to the importance of symptom control, comprehensive patient evaluations should be performed at regular intervals to determine the extent of neurological damage and disease progression and to address changing patient needs. The goal of interventions should be not only to treat the primary and secondary symptoms of MS but also to provide access to the psychosocial support that will help MS patients and their families continue to cope as disease status changes.     

Psychotic symptoms in Alzheimer disease: evidence for subtypes.

OBJECTIVE: Psychotic symptoms in Alzheimer disease (AD) identify a phenotype with distinct neurobiology and genetic architecture. The authors investigated whether AD with psychosis is homogeneous or is a composite of subtypes. METHODS: Authors performed factor and cluster analyses of the psychotic-symptom items of the CERAD Behavioral Rating Scale in 188 probable and possible AD subjects who have displayed at least one psychotic symptom. RESULTS: Exploratory factor analysis resulted in a one-factor solution that comprised misidentification delusions, auditory and visual hallucinations, and the misidentification of people. Persecutory delusions were also frequently present and were independent of the misidentification/hallucination factor. Cluster analysis yielded similar results. CONCLUSION: Misidentification/hallucinations and persecutory delusions may identify two subtypes of psychosis in AD. Longitudinal study is needed to determine whether these proposed subtypes remain stable and independent over time or merge into a single group over the course of illness.     

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease.

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.     

Effect of neuropsychiatric symptoms of Alzheimer's disease on Chinese and American caregivers.

BACKGROUND: In Chinese culture, extended family support, acceptance of age-related cognitive changes and filial tradition of caring for elders may decrease caregiver burden and distress in the context of dementia. OBJECTIVE: To study cross-regional and cross-cultural differences in symptom-related caregiver distress due to the behavioral problems of Chinese and American patients with Alzheimer's disease. METHOD: Caregivers of patients with Alzheimer's disease at Taipei Veterans General Hospital, Taiwan (n = 89), Chinese University of Hong Kong (n = 31) and the UCLA Alzheimer's Disease Research Center, Los Angeles, California (n = 169) reported the neuropsychiatric symptoms of patients and their corresponding distress on the Neuropsychiatric Inventory. RESULT: Presence or absence of distress due to the neuropsychiatric symptoms of the patients with Alzheimer's disease was assessed. The three centers differed significantly in the proportions of caregivers with distress caused by depression (p < 0.05) and apathy (p < 0.001). UCLA had higher proportions of caregivers with depression-related distress than Taipei. UCLA caregivers were also more stressed by apathy than caregivers in Taipei and Hong Kong. Logistic regression further supported the findings that depression-related and apathy-related caregiver distress differed between Chinese and American caregivers (p < 0.05). CONCLUSIONS: The results were surprising, in that American and Chinese (Taipei and Hong Kong) caregivers exhibited similar distress or lack of distress in response to delusions, hallucinations, agitation, anxiety, euphoria, disinhibition, irritability, aberrant motor behavior, sleep and appetite symptoms of Alzheimer's disease patients. Chinese caregivers were less affected by depression and apathy in patients with Alzheimer's disease than Caucasian caregivers.     

Pharmacologic management of agitation in Alzheimer's disease

A large body of evidence has accrued that neuropsychiatric disturbances, such as agitation, are extremely common in Alzheimer's disease. These disturbances are associated with considerable morbidity including earlier nursing home admission, more rapid progression, exacerbation of functional and cognitive deficits, and increased caregiver distress. When attention to social or environmental causes, medical conditions, or other triggers of the behavioral disturbance fails to yield improvement, a role for medication may be indicated, whereby the most dominant behavioral target symptoms are matched to the most relevant medication class. Evidence is reviewed for various medication classes in treating agitation in the patient with Alzheimer's disease, and future treatment strategies may be aimed at delaying or preventing such neuropsychiatric disturbances.     

Pharmacologic management of psychiatric and behavioral symptoms in mental retardation

Compared with the general population, individuals with mental retardation demonstrate more susceptibility to psychiatric illness and may display disruptive behaviors. These symptoms significantly can affect an already compromised ability to function and the patient may benefit from pharmacologic intervention. Clinical characteristics of individuals with mental retardation warrant special consideration regarding diagnosis and treatment of their psychiatric and behavioral problems. This article describes the nature of symptoms that are typically the target of pharmacologic intervention, outlines special diagnostic considerations, and examines recent findings and experience with psychotropic medication in mental retardation.     

Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease

Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome and/or a “risk factor” of neurodegenerative diseases. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer's disease (AD) and Parkinson's disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.     

Cholinesterase inhibitor therapy stabilizes symptoms of Alzheimer disease

Cholinesterase inhibitors tested in clinical trials in Europe, the United States, and Japan include fewer than 10 drugs; however, most of these compounds have advanced to clinical phase III trials. Based on results related to a population of more than 8,000 patients, we conclude that several of these compounds have shown significant clinical efficacy and safety in the treatment of Alzheimer disease. There are, however, differences with regard to side effects. The major clinical effect is stabilization of cognitive function during a 6- to 12-month period with an improvement of behavioral symptoms. The long-term effect of cholinesterase inhibitors extending to a 2-year period was reported. Future applications of these drugs include treatment of other types of dementias such as Lewy bodies dementia, vascular dementia, and Down syndrome dementia. The combination of cholinesterase inhibitors with estrogens, antioxidants, and anti-inflammatories may represent a further improvement of the therapy. From an economical point of view, treatment with cholinesterase inhibitors is not cost neutral.