Effects of aging on behavioral symptoms in Alzheimer's disease

Aim:  The aim of the present study was to evaluate the relationship between aging and the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD).
Methods:  Eligible subjects were consecutively referred AD patients with BPSD. According to patient age at the time of the test, the AD patient group ( n  = 79, whole AD group (WADG)) was divided into two groups: a relative older group (OG) in the whole AD group (WAD) (age at the time of test was 81 years or more, n  = 40) and a relative younger group (YG) in the WAD (age at the time of test was below 81 years, n  = 39). A comparison was made of the demographic data (sex difference, educational level and severity of dementia), cognitive functions and BPSD between the groups. BPSD was evaluated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). The factor analysis of BPSD was conducted in the WADG as well as in the OG and YG.
Results:  Sex difference, educational level, severity of dementia and cognitive functions were not different; however, the total score of the BEHAVE-AD symptom domain in diurnal rhythm was significantly higher in the OG than in the YG (Student's t -test: P  < 0.05). Factor analysis showed that psychosis was the first factor in the OG, but was the third factor in the YG and that the psychotic symptoms were caused by anxieties and phobias in the OG.
Conclusion:  From these results, we found that the effects of aging on the BPSD in AD were characterized by diurnal rhythm disturbance and psychosis.     

Behavioral and psychological symptoms of dementia in untreated Alzheimer's disease patients

Background: To ascertain the prevalence of psychotic symptoms and behavioral disturbances of dementia patients is useful for families and health care professionals in order to anticipate the progression of Alzheimer’s disease (AD) and to recognize deterioration. This study aimed to determine whether behavioral and psychological symptoms of dementia (BPSD) are related to severity of untreated AD. Methods: Two hundred and two patients were classified into three groups by Functional Assessment Staging score as follows: mild group (n = 92) was at stages 3 or 4; moderate group (n = 80) was at stage 5; and severe group (n = 30) was at stages 6 or 7. We then compared the prevalence of BPSD among the groups. Psychiatric symptoms of BPSD were defined as including hallucinations, delusions, delusional misidentification syndrome and depressive mood; while behavioral disturbances included physical aggression, wandering, adverse sleep and hyperphagia. Results: In our study, depressive mood, physical aggression and wandering were statistically associated with the severity of AD. Conclusion: These results are meaningful for caregivers in helping them to understand the anticipated progression of AD and to recognize deterioration. In the care of AD patients, it is necessary to be aware of characteristics of each BPSD.     

Characteristics of behavioral and psychological symptoms in the oldest patients with Alzheimer's disease

Background: Advancing age increases the risk of developing dementia. Recent studies have clarified characteristic cognitive changes in very old patients with dementia. Although non‐cognitive symptoms are frequent in dementia, relatively little attention has been paid to the nature of behavioral and psychological symptoms of dementia (BPSD). Methods: A retrospective review of a database was performed to compare 27 very old patients with Alzheimer's disease (AD) (onset age ≥ 85) with 162 less old patients (onset age < 85). Cognitive decline, ability to carry out activities of daily living (ADL), and overall severity were rated. BPSD were evaluated using a 16‐item questionnaire to the compare frequency of each symptom between old and very old groups. Results: Cognitive decline was equivocal in both old and very old groups. In contrast, very old patients were more impaired in ADL, and BPSD were more frequent in very old patients. Delusions, irritability, and delusional misidentification syndrome were frequent in both groups, but were more prominent in very old patients. Behavioral abnormalities such as excitement, delirium, reversed diurnal rhythm, and wandering were not prominent in old patients, but were frequent in very old patients. Conclusions: Very old AD patients presented more frequent BPSD than old AD patients. Troublesome behavioral abnormalities particularly prominent in the older patients might represent a heavy burden for caregivers.     

阿尔茨海默病精神行为症状复发的危险因素和特征

目的探讨阿尔茨海默病(Alzheimer's disease,AD)患者精神行为症状(behavioral and psychologicalsymptoms of dementia,BPSD)复发的危险因素和特征。方法收集102例以BPSD发作就诊的AD患者,在BPSD发作控制后进行12个月的随访。BPSD的严重程度应用神经精神量表(neuropsychiatric inventory,NPI)评估,并将NPI因子归类为情感障碍、精神病性症状和失控行为3个症状群。分析BPSD复发与先前发作的特征,复发与患者人口学资料、发病年龄、病程、认知功能、日常生活能力、基线NPI评分等因素的关系。结果 12个月内44.1%(45/102)的患者BPSD复发。Cox回归分析显示,环境改变(RR=5.42,P<0.05)、未维持服药(RR=3.13,P<0.05)和上次发作NPI评分高(RR=1.06,P<0.05)增加BPSD复发的风险;两次BPSD发作之间的症状数相关(r=0.93,P<0.05),而情感障碍评分也相关(r=0.79,P<0.05);复发的NPI总分和精神病性症状评分均低于上次发作[(18.29±2.0...     

老年性阿尔茨海默病与血管性痴呆患者的行为和精神症状的比较

目的探讨阿尔茨海默病痴呆患者的行为和精神症状。方法选取本院2011年5月至2015年5月诊治的痴呆性老年患者80例,其中血管性痴呆(VD)患者40例为VD组,阿尔茨海默病(AD)患者40例为AD组,均行AD行为评分表(Behave-AD)评定,比较两组患者的行为和精神症状。结果 AD组患者偏执和妄想发生率、行为紊乱发生率、攻击行为发生率、焦虑和恐惧发生率均明显高于VD组,AD组患者偏执和妄想评分、行为紊乱评分、攻击行为评分、焦虑和恐惧评分、总评分均明显高于VD组,差异有统计学意义(P0.05)。AD组患者幻觉发生率高于VD组,AD组患者日间节律紊乱发生率、情感障碍发生率均低于VD组,AD组患者幻觉评分高于VD组,AD组患者日间节律紊乱评分、情感障碍评分均低于VD组,但差异无统计学意义(P0.05)。结论 AD患者偏执和妄想、行为紊乱、攻击行为、焦虑和恐惧等病症较为严重,其发生机制可能与AD患者存在较明显的额-枕叶萎缩有关。     

Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer's disease

BACKGROUND: When comparing with early-onset Alzheimer's disease (EO-AD) and late-onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups. AIM: The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups. METHOD: Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment. RESULTS: Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups. CONCLUSION: In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment. Copyright (c) 2007 John Wiley & Sons, Ltd.     

A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease

BACKGROUND: Non-cognitive symptoms are a frequent feature of Alzheimer's disease (AD). Much of the literature that has accumulated pertains to cross-sectional prevalence of these symptoms. There has been relatively little attention paid to the longitudinal course of Behavioural and Psychological Symptoms of Dementia (BPSD). AIMS: The purpose of this study is to examine the longitudinal course of BPSD in a group of patients with mild AD. METHODS: A retrospective review of a database was performed to identify patients with NINCDS/ADRDA criteria for probable AD and who had been evaluated three times at yearly interval over a two-year period. Fifty-two subjects were identified with probable AD that had completed follow-up for 24 months. The BEHAVE-AD was used to evaluate BPSD and data was analysed using a Markov analysis. RESULTS: Activity disturbance is a common and relatively persistent symptom in the mild stages of AD. Anxiety, paranoid ideation, and aggression were moderately persistent. Affective symptoms were not persistent with less than half the patients having the symptoms a year later. CONCLUSIONS: Activity disturbance is common and persistent in early AD. Paranoid and delusional ideation shows moderate persistence and depressive symptoms infrequently last longer than a year. These findings may have clinical relevance for the pharmacological and non-pharmacological management of BPSD.     

Glutamate/glutamine concentrations in the dorsal anterior cingulate vary with Post-Traumatic Stress Disorder symptoms

Trauma and stress-related disorders (e.g., Acute Stress Disorder; ASD and Post-Traumatic Stress Disorder; PTSD) that develop following a traumatic event are characterized by cognitive-affective dysfunction. The cognitive and affective functions disrupted by stress disorder are mediated, in part, by glutamatergic neural systems. However, it remains unclear whether neural glutamate concentrations, measured acutely following trauma, vary with ASD symptoms and/or future PTSD symptom expression. Therefore, the current study utilized proton magnetic resonance spectroscopy (¹H-MRS) to investigate glutamate/glutamine (Glx) concentrations within the dorsal anterior cingulate cortex (ACC) of recently (i.e., within one month) traumatized individuals and non-traumatized controls. Although Glx concentrations within dorsal ACC did not differ between recently traumatized and non-traumatized control groups, a positive linear relationship was observed between Glx concentrations and current stress disorder symptoms in traumatized individuals. Further, Glx concentrations showed a positive linear relationship with future stress disorder symptoms (i.e., assessed 3 months post-trauma). The present results suggest glutamate concentrations may play a role in both acute and future post-traumatic stress symptoms following a traumatic experience. The current results expand our understanding of the neurobiology of stress disorder and suggest glutamate within the dorsal ACC plays an important role in cognitive-affective dysfunction following a traumatic experience.     

Characteristics of behavioral and psychological symptoms of dementia in untreated oldest old Alzheimer's disease*

Background: The proportion of the population aged 85 years and older has increased rapidly in Japan, reaching 2.5 million (1.99%) in 2002. Under these circumstances, the number of dementia patients increases annually. However, few studies have focused on Alzheimer's disease (AD) with an age at onset older than 85 years (oldest old AD). The aims of the present study were to determine the prevalence of the behavioral and psychological symptoms of dementia (BPSD) in patients with oldest old AD compared with those with young old AD. Methods: Fifty‐eight untreated AD patients were divided into two groups: young old AD patients (age at onset between 65 and 70 years; n = 28) and oldest old AD patients (age at onset 85 years or older; n = 30). Then, BPSD were compared between the two groups. Results: There were significant differences in the frequencies of hallucinations (χ² = 7.43; P = 0.011) and delusional misidentification syndrome (DMS; χ² = 7.26; P = 0.011) between the two groups. Conclusions: The results of the present study suggest that aging may play a part in the occurrence of hallucinations and DMS in oldest old AD patients.     

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia

Objectives: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD).

Method: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment.

Results: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis.

Conclusion: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease

Objective

The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD).

Methods

Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D₂ selective antipsychotic, was performed for 12 weeks.

Results

Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted.

Conclusions

Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.     

Alzheimer病患者发病前后认知功能改变及预测因子的研究

目的 研究Alzheimer病(AD)患者发病前后认知功能的改变及发病预测因子.方法 于2004年对46例AD患者(2000年未发病)及167名正常老年人(正常对照组)采用简易精神状态检查(MMSE)量表进行检查,并与2000年的检查结果比较.用Logistic多元回归分析寻找AD预测因子.结果 AD组2000年的MMSE量表执行、时间定向、空问定向、延迟记忆、计算、注意亚项以及总分显著低于正常对照组(P＜0.05～0.01),阅读、命名、识记、构图、书写得分与正常对照组差异无统计学意义;2004年仅命名得分与正常对照组差异无统计学意义,其他各项得分均显著低于正常对照组(P＜0.05～0.01).AD组2004年MMSE的命名、构图、时间定向、空间定向得分和总分显著低于2000年(均P＜0.05).正常对照组2004年命名、构图、时间定向得分显著低于2000年(均P＜0.05),其余各亚项以及总分与2000年差异无统计学意义.将两组2000年与2004年MMSE得分的差值进行秩和检验,AD组识记、时间定向、空间定向和延迟记忆得分差值平均秩次显著大于正常对照组(均P<0.05);AD组以上亚项得分的下降程度大于正常对照组.Logistic多元回归分析,空间定向和延迟记忆亚项的OR值分别为2.12和1.49(P＜0.001,P＜0.05),为AD独立的预测因子.结论 AD患者在临床发病之前其时间定向、空间定向、延迟记忆、计算、注意、执行得分已经明显降低;发病后又出现命名、构图得分下降.老年人MMSE空间定向和延迟记忆得分下降是提示有发生AD危险的预测因子.     

Alzheimer病患者扣带回后部损害磁共振扩散张量成像的研究

目的探讨Alzheimer病(AD)患者扣带回后部磁共振扩散张量成像(DTI)的特点及其与认知功能改变的相关性。方法对16例AD患者和12名健康老人(正常对照组)行DTI、T1Flair及T2Flari检查,测量扣带回后部各向异性分数值(FA)、平均弥散度(MD)及其λ1、λ2及λ33个特征值,分析上述诸项数值与简易精神状态检查量表(MMSE)评分之间的相关性。结果与正常对照组相比,AD组患者扣带回后部的FA值显著降低(P<0.05),而MD、λ1、λ2及λ3值明显升高(均P<0.05);FA值与MMSE评分不相关(r=-0.054,P>0.05),而MD值与MMSE评分呈显著负相关(r=-0.664,P<0.01);λ1、λ2及λ3值均与MMSE评分呈负相关(r=-0.643,r=-0.69,r=-0.654,均P<0.01)。结论AD患者表现为扣带回后部各向异性损害,且损害程度与临床认知功能评分呈负相关;这种损害反映了AD病理机制中皮质-皮质及皮质-皮质下联系的丢失;DTI可以用来监测AD疾病的进展及评价药物的临床疗效。     

Repetition priming in aging and Alzheimer's disease: an integrative review and future directions

Two decades of research examining repetition priming in aging and Alzheimer's disease (AD) has yielded a large body of contradictory findings due to differences between studies in participant and task characteristics. Recent research that has employed methodological advances indicates that this form of implicit memory is preserved in healthy aging. When a priming deficit does occur in studies of aging, it is likely a very early signal of neurological disease. Future directions for research in this area include linking priming ability to known risk factors for development of AD, integrating priming measures into clinical neuropsychological assessment batteries, and implementing programs of cognitive retraining that enhance memory using stimulus repetition techniques.     

Cognitive phenotypes in Alzheimer's disease and genetic risk

Variation in the clinical characteristics of patients with Alzheimer's disease (AD) is increasingly recognised, although the factors underlying variation are not fully understood. The study examined the cognitive characteristics of 523 AD patients at the time of their presentation to a neurological dementia clinic and explored the relationship to family history and apolipoprotein E (APOE) genotype. Distinct profiles were identified, which were mirrored by topographical differences on neuroimaging. Clinical distinctions were maintained over time. Two-thirds of patients showed a constellation of deficits at presentation which included memory, language, visuospatial and constructional difficulties. However, a quarter had circumscribed presentations of amnesia, aphasia, perceptuospatial disorder or apraxia. The rare presence of frontal lobe characteristics was associated with a younger age of onset, an increased incidence of myoclonus at presentation, a positive family history but not with possession of APOE epsilon4 allele. An amnestic presentation (severe, yet circumscribed amnesia) was strongly associated with an older age of onset, a positive family history and the presence of APOE epsilon4 allele. Posterior cortical presentations showed a female bias, were typically sporadic, and showed no association with APOE epsilon4. The findings support the notion of phenotypic variation in AD, and show that genetic risk factors can influence clinical presentation. The findings draw attention to the specific association between APOE epsilon4 allele and memory but challenge the commonly held notion that the presence of the epsilon4 allele inevitably reduces onset age. The findings indicate that risk factors other than APOE epsilon4 allele underlie the non-familial, early onset posterior hemisphere presentations of AD.     

Post‐marketing survey of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD)

Background: To investigate the efficacy and safety of donepezil hydrochloride (Aricept^®; Eisai Co., Ltd, Tokyo, Japan), we conducted a post‐marketing survey in Japanese patients with Alzheimer's disease (AD) who also had behavioral and psychological symptoms of dementia (BPSD), such as hallucinations/delusions, wandering, and aggression, which cause the greatest burden on caregivers. Methods: A prospective, centrally registered investigation was conducted through regular clinical settings with patients diagnosed as mild to moderate AD presenting with hallucinations/delusions, wandering, and/or aggression. The treatment period was 12 weeks and no restrictions were placed on concomitant medications. Results: The BPSD improvement rates at last‐observation‐carried‐forward (LOCF) were 60.1% for hallucinations/delusions, 59.6% for wandering, and 65.6% for aggression. For all symptoms, improvement rates increased with the duration of the treatment period. The BPSD deterioration rates at LOCF were 1.3% for hallucinations/delusions, 3.4% for wandering, and 1.6% for aggression. Assessment of cognitive function with both the revised Hasegawa Dementia Scale (HDS‐R) and Mini‐Mental State Examination (MMSE) indicated significant improvements after treatment. There were significant differences in the changes in HDS‐R scores between patients whose hallucinations/delusions or wandering were improved and patients whose symptoms were not improved. Moreover, the data suggested a possible correlation between changes in hallucinations/delusions and HDS‐R scores, changes in hallucinations/delusions and MMSE scores, and changes in wandering and MMSE scores. Patients in whom BPSD improved also demonstrated a greater improvement in cognitive function compared with patients in whom no improvement in BPSD was noted. Nursing burden on caregivers at LOCF showed 3.6% for ‘No burden’, 54.1% for ‘Burden decreased’, and 4.5% for ‘Burden increased.’ There was an increase in the combined ratio of ‘No burden’ and ‘Burden decreased’ in proportion with prolonged treatment period. Patients with improved BPSD had a significantly greater ratio (88.5–94.4%) of ‘No burden’ plus ‘Burden decreased’ than those patients in whom no improvement in BPSD was noted. Conclusions: These results suggest that donepezil not only improves the cognitive dysfunction of AD patients, but may also relieve BPSD in these patients. Treatment with donepezil was also found to alleviate the burden of caregivers for approximately 60% of patients. Moreover, the results indicate that donepezil is unlikely to trigger potential risks of excessive deterioration of BPSD, which would result in a heavier burden of nursing care.