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.     

Five Alzheimer's disease cases with refractory behavioural psychological symptoms of dementia treated with blonanserin

The aim of the present study was to determine the efficacy, side‐effects and tolerability of blonanserin for treating refractory behavioural psychological symptoms of dementia (BPSD). The present study was a 12‐week, prospective, structured clinical trial of blonanserin for the treatment of BPSD. The degree of cognitive function, activities of daily living score, and the degree of BPSD were determined using the Mini‐Mental State Examination (MMSE), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). The severity of extrapyramidal symptoms was assessed using the Drug‐Induced Extrapyramidal Symptoms scale (DIEEPS). Five patients were enrolled. These patients met the NINCDS‐ADRDA criteria. The patients were prescribed more than two kinds of existing antipsychotic drugs and were considered refractory cases; the drugs were discontinued because they were ineffectual and side‐effects appeared. Each drug was prescribed independently for at least 2 weeks. The mean changes (at baseline and at the last week, respectively) in the MMSE (12.25, 9.25), in the DAD (6.5, 6.75), in the RAGE (5.5, 5.3) and in the DIEEPS (0.5, 1.5) were minimal. The mean changes in the NPI were two or fewer points. Some side‐effects (one gait abnormality and one pneumonia) were observed. The results of this preliminary study show that blonanserin does not have adequate efficacy for the treatment of refractory BPSD.     

Fragmentation of activity periods in Alzheimer's disease

Activity cycles were studied in 12 subjects clinically diagnosed with Alzheimer's disease. Subjects wore a movement sensor attached to a solid-state ambulatory monitor for 96 consecutive hours each. Varying degrees of fragmentation of the normal diurnal activity pattern were observed. Subject variables such as age, estimated duration of illness, cognitive ratings, and months since first admission were compared for degree of association with the movement data. Simple regression analyses showed that an estimate of the duration of illness was superior to others in predicting the degree of fragmentation in activity rhythms. Pathology in the suprachiasmatic nucleus of the hypothalamus is discussed in the light of these findings.     

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.     

The behavioral pathology in Alzheimer's disease scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients

Objective. The aims of this study were to (a) determine the factor structure of the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), and (b) examine the associations of the observed factors to the level of cognitive impairment. Design. Cross-sectional study of geriatric patients evaluated at an outpatient memory disorders clinic. Sample. One hundred and fifty-one consecutive patients diagnosed with Alzheimer's disease (AD) according to NINCDS–ADRDA diagnostic criteria. Results. Principal factors analysis with Varimax rotation resulted in a five-factor solution that accounted for 40·0% of the common variance. The factors included agitation/anxiety (agitation, anxiety of upcoming events; other anxiety), psychosis (delusions of theft, suspiciousness/paranoia; visual hallucinations), aggression (verbal aggressiveness; physical threats/violence; fear of being left alone; other delusions), depression (tearfulness; depressed mood) and activity disturbance (wandering; delusion one's house is not one's home). Several factors were associated with level of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE). Conclusion. The results of this study suggest that the BEHAVE-AD measures a wide range of behavioral pathology that can be empirically represented by five independent symptom clusters among outpatient AD patients. Copyright © 1998 John Wiley & Sons, Ltd.     

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.     

Behavioral profile of Alzheimer's disease in Chinese elderly--a validation study of the Chinese version of the Alzheimer's disease behavioral pathology rating scale

OBJECTIVES: This study aims to examine the psychometric properties of the Chinese version of the Alzheimer's disease behavioral pathology rating scale (CBehave-AD) and the behavioral profile of Chinese patients with AD. METHODS: Seventy-one subjects with NINCDS-ADRDA diagnosis of probable and possible AD were assessed for validation of the CBehave-AD. A behavioral symptom frequency checklist, the Chinese version of the Blessed Roth dementia scale (CDS) and the Cantonese version of the Mini-Mental State Examination (CMMSE) were used for comparison. An extended sample of 120 AD patients was then evaluated with the CBehave-AD. RESULTS: High correlations between the CBehave-AD and checklist scores were found (paranoid and delusional ideation, hallucinations, activity disturbances, aggressiveness and diurnal rhythm disturbances). The scale also demonstrated satisfactory inter-rater and test-retest reliabilities. The mean (SD) CMMSE score of the 120 patients was 9.4 (7.1). Among them, 32% have delusions, 15% had hallucinations, 54% had activity disturbances, 61% had aggressive behavior, 44% had sleep disturbance, 24% had affective disturbances, 19% had anxiety and phobias. Delusional ideation was significantly associated with hallucinations, aggressiveness, and affective disturbances. Diurnal rhythm disturbances were associated with activity disturbances and aggressiveness. CBehave-AD total scores were not significantly correlated with severity of AD, but individual symptom categories showed different pattern of correlation. Delusions, hallucinations, anxiety and phobias were significantly correlated with dementia staging. CONCLUSION: The findings suggest that the CBehave-AD is a valid assessment tool for behavioral disturbances in patients with AD. Variable associations between different symptom categories and dementia staging suggest a need for further exploration of the complex interactions between behavioral and cognitive disturbances in dementia.     

Incidence and relationship between behavioural and psychological symptoms in Alzheimer's disease

Objectives. To evaluate the frequency and type of psychological and behavioural symptoms in Alzheimer's disease (AD) patients in Poland, in various stages of the disease. Method. One hundred and sixty-nine patients with a diagnosis of probable AD in Global Deterioration (GDS) stages 3, 4, 5, 6 and 7 of dementia were examined in a search for behavioural and psychological symptoms. Results. Behavioural and psychotic symptoms were most often found in GDS stages 5 and 6 of AD, except for depressive disorder, which was observed most frequently in GDS stage 4 and whose frequency decreased towards the terminal stages of dementia. From an analysis of the relationship between behavioural symptoms in the Polish AD patients, the following syndromes may be discriminated: psychotic syndrome (delusions and hallucinations), delusions with aggressive behaviour and hallucinations and anxiety. With more severe dementia, the syndromes, which could be the result of delirium, became more common. Conclusions. Diagnosis of delirium should be considered in moderately severe and severe dementia whenever a sudden change in patients' behaviour occurs. Copyright © 1998 John Wiley & Sons, Ltd.     

Syndromes of behavioural and psychological symptoms in mild Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are common in Alzheimer's disease (AD), and are associated with significant distress for patient and carer. Certain behavioural and psychological symptoms have been associated with each other, leading to the suggestion that differences in symptom patterns among patients with AD may represent different syndromes within AD. The purpose of this study is to see if patients with AD could be meaningfully classified into syndromes, based on the relationships between their BPSD. METHODOLOGY: The sample was recruited through a memory clinic. Two hundred and forty first visit patients with a diagnosis of very mild to mild AD were included. BPSD were assessed using the BEHAVE-AD. Latent class analysis was used to assess for different classes or groups of patients within the sample, based on their behavioural and psychological symptoms. RESULTS: Three classes were identified; Class 1 with a low prevalence of behavioural and psychological symptoms; Class 2 an anxiety/depressive symptom class and Class 3 an aggressive symptom class. CONCLUSIONS: The three classes (or groups) of patients obtained by LCA in this sample may be explained by a 'latent', as yet, unidentified factor. Further research is required to determine if these classes are stable over time, and to identify possible latent variables.     

Glycation in Parkinson's disease and Alzheimer's disease

Glycation is a spontaneous age‐dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α‐synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society     

SPECT findings in Alzheimer's disease and Parkinson's disease with dementia

We examined, with single photon emission tomography (SPECT) and (^99mTc)-HMPAO, 18 patients with idiopathic Parkinson's disease and no dementia (PD), 12 patients with PD and dementia, 24 patients with probable Alzheimer's disease (AD) and 14 controls. While the three patient groups showed significantly lower perfusion in frontal inferior and temporal inferior areas as compared to controls, both demented groups showed significantly more severe bilateral hypoperfusion in superior frontal, superior temporal and parietal areas as compared to non-demented PD patients and controls. On the other hand, no significant differences in cerebral perfusion were found between patients with AD and patients with PD and dementia. In conclusion, our findings demonstrated specific but similar cerebral perfusion deficits in demented patients with either AD or PD.     

Clinical predictors of aggressive behaviour in Alzheimer's disease

Objectives. To examine the level and clinical correlates of aggressive behaviour in Alzheimer's disease (AD). Method. Seventy patients with probable AD were rated using validated assessment instruments including the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). Results. Thirty-one subjects were rated as at least mildly aggressive during the 3-day period prior to assessment. RAGE scores correlated significantly with delusions and activity disturbance scores. Aggressive behaviour was not associated with age, sex, dementia severity, hallucinations or depression. Conclusions. Aggressive behaviour occurs frequently in patients with AD. Our results confirm the findings of previous studies that the presence of delusions increases the risk of aggression in this population. © 1998 John Wiley & Sons, Ltd.     

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.     

Oligodendrocytes and Alzheimer's disease

Extensive evidence has indicated that the breakdown of myelin is associated with Alzheimer's disease (AD) since the vulnerability of oligodendrocytes under Alzheimer's pathology easily induces the myelin breakdown and the loss of the myelin sheath which might be the initiating step in the changes of the earliest stage of AD prior to appearance of amyloid and tau pathology. Considerable research implicated that beta-amyloid (Aβ)-mediated oligodendrocyte dysfunction and myelin breakdown may be via neuroinflammation, oxidative stress and/or apoptosis. It also seems that the oligodendrocyte dysfunction is triggered by the formation of neurofibrillary tangles (NFTs) through inflammation and oxidative stress as the common pathophysiological base. Impaired repair of oligodendrocyte precursor cells (OPCs) might possibly enhance the disease progress under decreased self-healing ability from aging process and pathological factors including Aβ pathology and/or NFTs. Thus, these results have suggested that targeting oligodendrocytes may be a novel therapeutic intervention for the prevention and treatment of AD.     

Alzheimer's disease in real life--the dementia carer's survey

BACKGROUND: Informal care from relatives provides the foundation of care for people with Alzheimer's disease (AD). It is important to understand the conditions under which carers perform their, often neglected, task. The dementia carer's survey aimed to identify carers' needs, differences between countries with regard to dementia care and the level of satisfaction of carers with utilised services. METHODS: The survey was conducted through Alzheimer Europe's member organisations in France, Germany, Poland, Spain and UK (Scotland). The survey was in the form of a questionnaire, and topics addressed included: demographics of carers and people with AD; time spent caring; disclosure of diagnosis; symptoms prompting diagnosis; diagnostic process; current and most distressing symptoms; carers' information requirements; evaluation of services. RESULTS: Each country had approximately 200 responders. Time spent caring increases with disease severity, and 50% of carers of people with late-stage dementia spent more than 10 h/day caring. Activities of daily living and behaviour were cited as the most problematic symptoms, reported by 68% and 50% of carers, respectively. Provision of information on all aspects of AD was felt to be inadequate, with key services such as home support not available to the majority of carers. Only 17% of carers considered the level of care for the elderly in their country as good. CONCLUSIONS: Further development of services and information provision are required to help carers in their everyday caring, including coping with problematic symptoms influencing areas such as activities of daily living and behaviour.     

Adult neurogenesis in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbances. The hippocampus, where adult hippocampal neurogenesis (AHN), a relatively novel form of brain plasticity that refers to the birth of new neurons, occurs, is one of the first brain regions to be affected in AD patients. Recent studies showed that AHN persists throughout life in humans, but it drops sharply in AD patients. Next questions to consider would be whether AHN impairment is a contributing factor to learning and memory impairment in AD and whether restoring AHN could ameliorate or delay cognitive dysfunction. Here, we outline and discuss the current knowledge about the state of AHN in AD patients, AHN impairment as a potentially relevant mechanism underlying memory deficits in AD, therapeutic potential of activating AHN in AD, and the mechanisms of AHN impairment in AD.