Enjeux et moyens du suivi des malades souffrant de la maladie d’Alzheimer

The following article presents the main points of the follow-up plan of Alzheimer's disease (AD) and related syndromes patients. The general objective of this follow-up plan is to improve the quality of live of these subjects and their family. The key points are assessments of cognitive decline, functional decline and complications such as behavioural and psychological symptoms of dementia (BPSD), malnutrition and gait and balance disorders. In clinical practice, different tools are available, but frequency of evaluation is not consensual. However, the aim of this follow-up is to detect, prevent and treat complications and to improve the use of residual functional abilities in basic activities of daily living. The physician also needs to detect and prevent caregiver's exhaustion and to consider the ethical issues raised by the disease. The care plan is based on non pharmacological and pharmacological measures. The non pharmacological approach must be implemented first. The place of antidementia drugs is considered. Lastly, this follow-up plan aims to limit iterative admissions to emergency room and to increase the access to geriatric units. Communication and collaboration between specialist, family practitioner and caregivers are needed in order to reach the objective of quality of life improvement in AD patients.     

Behavioral and psychological symptoms, cognitive impairment and caregiver burden related to Alzheimer's disease patients treated in an outpatient memory clinic

AIM: The relationships among behavioral and psychological symptoms of dementia (BPSD), cognitive impairment of Alzheimer's disease (AD) patients and the caregiver burden of their caregivers were investigated in an outpatient memory clinic. METHODS: Forty-six pairs of AD patients and their family caregivers were involved in this study. Neuropsychiatry Inventory (NPI) was used to estimate BPSD, to which memory symptoms were added as a subcategory of BPSD. MMSE, word fluency, clock drawing test and category-cued memory test were used for cognitive measurement. Zarit burden interview (ZBI) and CES-D were used to assess caregiver burden. RESULTS: Among 11 BPSD subcategories, memory symptoms, apathy, depression, delusion, aggression and anxiety were prevalent BPSD was a strong determinant of caregiver burden. Among BPSD symptoms, anxiety, aggression and aberrant motor behavior were significantly related to ZBL In terms of the relationship between BPSD and cognitive impairment, the scores for delusion and apathy were significantly related to the cognitive decline. On the other hand, patients who showed symptoms related to memory and depression had higher cognitive function than those who did not. CONCLUSION: These analyses will contribute to better assessment of AD patients and their caregivers, hopefully resulting in better support for them.     

Risk of falls in Alzheimer's disease: a prospective study

OBJECTIVE: Falls are common in patients with Alzheimer's disease (AD). Identification of the potential risk factors and developing preventive strategies for falls will have a significant impact in maintaining the quality of life in AD. PATIENTS: Clinical follow-up of 124 (74.1+/-6.1 years, range 62-88) mild to moderate AD patients in an outpatient memory clinic. METHODS: Postural sway, cognitive function, use of neuroleptics, severity of periventricular and deep white matter lesions, and the presence or absence of silent brain infarctions on magnetic resonance imaging were assessed at baseline. RESULTS: A total of 104 patients (84%) completed the study. Fall events were confirmed in 42.3% (44/104). After adjustment for age, gender, and cognitive status, a high grade of periventricular white matter lesions (odds ratio 8.7 [95%CI 1.5 to 51.8], p = 0.017) and neuroleptic drug use (odds ratio 3.5 [95%CI 1.2 to 10.5], p = 0.027) were significantly associated with an increased risk of falls. CONCLUSION: Our results suggest that periventricular white matter lesions and the use of neuroleptics may be related to falls in mild to moderate AD. A comprehensive risk management of brain ischemia as well as the use of the smallest efficacious dose of neuroleptics in the treatment of behavioral and psychiatric symptoms of AD should be recommended to help reduce the risk of unexpected falls.     

Management of the behavioral and psychological symptoms of dementia

More than 50% of people with dementia experience behavioral and psychological symptoms of dementia (BPSD). BPSD are distressing for patients and their caregivers, and are often the reason for placement into residential care. The development of BPSD is associated with a more rapid rate of cognitive decline, greater impairment in activities of daily living, and diminished quality of life (QOL). Evaluation of BPSD includes a thorough diagnostic investigation, consideration of the etiology of the dementia, and the exclusion of other causes, such as drug-induced delirium, pain, or infection. Care of patients with BPSD involves psychosocial treatments for both the patient and family. BPSD may respond to those environmental and psychosocial interventions, however, drug therapy is often required for more severe presentations. There are multiple classes of drugs used for BPSD, including antipsychotics, anticonvulsants, antidepressants, anxiolytics, cholinesterase inhibitors and NMDA modulators, but the evidence base for pharmacological management is poor, there is no clear standard of care, and treatment is often based on local pharmacotherapy customs. Clinicians should discuss the potential risks and benefits of treatment with patients and their surrogate decision makers, and must ensure a balance between side effects and tolerability compared with clinical benefit and QOL.     

Effects of rivastigmine on actigraphically monitored motor activity in severe agitation related to Alzheimer's disease: a placebo-controlled pilot study

Acetylcholinesterase inhibitors (AChEIs) are effective in the treatment of cognitive symptoms in Alzheimer's disease (AD). Because the behavioral and psychological symptoms of dementia (BPSD) have also been attributed to central cholinergic deficits, we examined whether the AChEI rivastigmine can reduce motor activity as measured in a rater-independent manner by wrist actigraphy in agitated AD patients. A total of 20 consecutive AD inpatients (13 females, 7 males, 80.4+/-9.1 years, S.D.) were included from our geriatric psychiatry unit, all of whom were exhibiting agitated behavior not attributable to delirium. Patients were assigned randomly and in a single-blinded fashion to rivastigmine 3mg or placebo for 14 days. Motor activity levels were monitored using an actigraph worn continuously on the wrist of the non-dominant hand. At the beginning and end of the study, patients were assessed using the Neuropsychiatric Inventory (NPI) and Nurses' Observation Scale for Geriatric Patients (NOSGER). Patients in the rivastigmine group exhibited less agitation than placebo recipients on the NPI-agitation subscale, but not on NOSGER. Actigraphic measurements showed a tendency towards reduced motor activity in the rivastigmine group. Because rivastigmine usually exerts its main effects after a longer period of time, the short-term effects seen in our study justify further controlled clinical trials examining the use of rivastigmine in BPSD by means of actigraphy.     

Acetylcholinesterase inhibitors and depressive symptoms in patients with mild to moderate Alzheimer's disease

BACKGROUND AND AIMS: Acetylcholinesterase inhibitor (AChEis) therapy in Alzheimer Disease (AD) has been shown to provide cognitive benefits and to slow progression of the disease. AChEis have also been demonstrated to improve behavioral symptoms, although there seem to be subtle differences in the magnitude of response. The aim of our study was to evaluate the effect of 16 weeks treatment with AChEis on depressive symptoms in a selected sample of AD patients in routine clinical practice. SUBJECTS AND METHODS: A study of 135 patients with Alzheimer's disease. All subjects were assessed at baseline (upon initiation of AChEis therapy) and re-evaluated after 16 weeks. RESULTS: At baseline, "Depressed" and "Not depressed" patients were categorized according to DSM IV criteria for depression in Alzheimer Disease. After 16 weeks of treatment with AchEis, we observed an improvement of mood in the "Depressed" patients. In this group "Mood symptoms", measured with GDS, were independently associated with GDS "Mood symptoms" at baseline, but not with improvement on cognition (mean change of MMSE), age or sex. CONCLUSIONS: In depressed AD subjects, AChEis treatment improves depressive symptoms evaluated by GDS. This improvement is independent of cognition enhancement.     

Rehabilitation outcome in home-based versus supervised exercise programs for chronically dizzy patients

The authors performed a cross-sectional study to examine the relationship between specific cognitive domains and behavioral and psychological symptoms in dementia (BPSD) in 125 patients with probable AD. Cognitive deficits were evaluated with the mini mental state examination (MMSE), trail-making test (TMT), Rey auditory verbal learning test (RAVLT), and semantic fluency test (SFT) and phonemic fluency test (PhFT), whereas the neuropsychiatric inventory (NPI) was used to rate BPSD. Patients’ performance in cognitive tests significantly correlated with total NPI scores (p < 0.0001). After controlling for demographic and clinical characteristics, cognitive impairments in memory, executive function, and language (RAVLT, TMT, PhFT, SFT) importantly estimated total NPI scores (p < 0.001, multivariate regression models). These findings suggest that the evaluation of cognitive domains may have a predictive value for the occurrence of BPSD.     

Behavioral and psychologic symptoms in Alzheimer's disease: results of the REAL.FR study

Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) are important manifestations of Alzheimer's Disease (AD) and other forms of dementia, because they are associate with care-giver distress, increase the likelihood of institutionalization, and may be associated with more rapid cognitive decline In this study (REAL.FR for Réseau sur la maladie d'Alzheimer Fran?ais) we prospectively used the Neuropsychiatric Inventory NPI to examine BPSD. 255 AD patients with a Mini-Mental State Examination (MMSE) score between 11 and 20 and 244 AD patients with a MMSE between 21 and 30 were examined. Factor analysis was carried out leading to three different syndromes according to the level of cognitive impairment. BPSD were detected in 92.5% of the patients with a MMSE between 11 and 20, and in 84% of the patients with a MMSE between 21 and 30. Apathy was the most common abnormality, followed by anxiety and dysphoria. These results in a French cohort of patients with AD underline the importance of the evaluation and finally of the treatment of BPSD.     

Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study

Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.     

痴呆及其心理、行为症状与血浆同型半胱氨酸水平关系

目的 探讨痴呆及痴呆心理和行为症状(Psychological and behavioral symptoms of dementia，BPSD)的可能发病机制，研究血浆同型半胱氨酸(homocysteine，Hcy)水平与痴呆及BPSD的关系。方法 阿尔茨海默病(Alzheimer Disease，AD)、混合性痴呆(Mixed dementia，MD)、血管性痴呆(Vascular dementia，VD)和正常对照组各30例参加本研究。采用Alzheimer病行为症状评定量表(The Behavioral Pathlology in Alzheimer Disease Rating Scale，BEHAVE-AD)评定痴呆患者BPSD。采用高压毛细血管电泳紫外检测法测定经2，4-二硝基氟苯(2，4-dimntrifluorobenzen，DNFB)衍生后的血浆Hcy水平。结果 AD、MD和VD患者血浆Hcy浓度均显著高于正常对照组，血浆高Hcy水平的痴呆患者BEHAVE-AD总分较高。结论 血浆高Hcy水平不仅与痴呆的发生发展有关，且在痴呆患者BPSD的发病机制中扮演了一个重要角色。     

Diagnosis, management, and treatment of Alzheimer disease: a guide for the internist

Alzheimer disease (AD) is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies; however, there is no definitive diagnostic test for AD. Early recognition of AD allows time to plan for the future and to treat patients before marked deterioration occurs. Effective treatment requires monitoring of symptoms, functional impairment, and safety, and the use of multiple treatment modalities including pharmacotherapy, behavioral management, psychotherapies, psychosocial treatments, and support and education for families. Pharmacotherapeutic agents available for AD only provide symptomatic relief. The cholinesterase inhibitors, tacrine and donepezil, are effective in improving cognition, delaying nursing home placement, and improving behavioral complications in some patients. Other cholinesterase inhibitors are in development, as are other cholinomimetic agents such as muscarinic and nicotinic receptor agonists. Symptomatic treatments are available for the psychiatric manifestations of AD. Anti-inflammatories, antioxidants, neurotrophic factors, and other agents are promising new treatments for the future.     

Behavioral and psychological symptoms in dementia with Lewy-bodies (DLB): frequency and relationship with disease severity and motor impairment

Clinical criteria for DLB have been more and more accurate over time, and they had focused on psychotic symptoms for their high frequency. Recent literature suggests that behavioral and psychological symptoms of dementia (BPSD) are frequently associated with DLB, beyond the presence of psychosis. Notwithstanding, the occurrence of BPSD in DLB is under-investigated, and no data are available yet in the different stages. Aim of the present study was to evaluate BPSD pattern in the different stages of DLB, and characterize the relationship with both cognitive deficits and Parkinsonian signs. Ninety-two DLB patients were enrolled and were divided into mild (n=63, 68.5%) and moderate-severe (n=29, 31.5%) subgroups according to the severity of cognitive impairment. Considering the absence/presence of symptoms, anxiety was the most common BPSD (67.4%), followed by depression (61.9%), apathy (57.6%), agitation and sleep disorder (55.4%). Psychosis was present in half of the patients. These symptoms worsened over disease course and represented a core-feature of the disease. No association between BPSD severity and the degree of motor disability was found. These observations suggest that a careful and systematic evaluation of BPSD is mandatory for carefully characterizing disease-related features and for developing new therapeutic approaches. Knowledge of the specific weight of BPSD in DLB would contribute to improve the allocation of health resources for dementia and to a better management of the disease.     

Brief checklist for non‐cognitive symptoms of dementia

Objective: To describe the development and psychometric utility of the behavioural and psychological symptoms of dementia (BPSD) checklist, a brief caregiver‐rated measure of the frequency of non‐cognitive symptoms of dementia of any type. Methods: Participants were 290 primary caregivers of patients referred to the Memory Clinic. Caregivers rated patients’ BPSD, cognitive symptoms and functional status. Patients underwent standardised cognitive evaluations. Results: High internal consistency reliability and good criterion and construct validity of the 14‐item BPSD checklist were established. Discussion: The BPSD checklist is a comprehensive, yet brief, psychometrically sound measure that may prove useful in both research and clinical settings.     

轻度阿尔茨海默病持续性注意功能的相关性研究

目的 了解轻度阿尔茨海默病(AD)患者注意功能损害情况及其相关因素. 方法 对68例轻度AD病患者在入组时、入组治疗8周后和100例健康老年人进行了连续操作试验(CPT)测试,以简易精神状态量表(mini-mental state examination,MMSE)和AD病理行为评分表(BEHAVE-AD)评定病情,并对测试结果、病程、病情严重度、年龄等进行回归分析. 结果 AD患者的所有CPT指标视觉单目标持续性注意测验(VOT)、视觉连续目标持续性注意测验(VST)、听觉持续性注意测验(ET)的漏答率、误答率、反应时间和变异系数均高于健康对照组,人组治疗8周后略有好转,但仍比健康人高,人组时CPT结果与病程、病情严重程度有关. 结论 AD患者注意损害广泛而严重,注意损害与病程、精神行为症状有关.     

Behavioral and psychological symptoms of dementia (BPSD) in elderly demented subjects: is the long lasting use of atypical antipsychotic drugs useful and safe?

The use of atypical antipsychotics (AA) is suggested in the treatment of BPSD, although controversial data are available on their safety and efficacy. The aim of this study was to assess the efficacy and safety of AA and whether this therapy could modify cognitive and functional domains in parallel with BPSD modifications. Out of 1,100 patients followed by the psychogeriatric ambulatory of our hospital, 69 patients (6.2%) were in therapy with AA and only 32 of them fulfilled the inclusion criteria of this study. Namely, the availability was required of a complete geriatric assessment, including the evaluation of cognitive (mini mental state examination=MMSE), emotional (the Italian "scala di valutazione del benessere emotivo nell'anziano"=SVEBA), functional (basic and instrumental activities of daily living=ADL and IADL), as well as behavioral (neuropsychological inventory=NPI) status, at the beginning (T(0)) and after a 6 month therapy (T(1)). The AA prescribed were risperidone (42.8%), olanzapine (31.3%), quetiapine (25.9%). The mean age was 80.1 years; 34.4% male; 65.6% female. Educational level was elementary in 90.6% of cases. Only 21.9% were institutionalized. 15.6% had 1 cardiovascular risk factor (CVRF), 50% more than 1, and the remaining with no CVRF. More than the half of them were diagnosed with degenerative dementia (D) (40.6% Alzheimer D=AD; 15.6% fronto-temporal dementia (FTD); 34.4% with vascular dementia (VD) (9.4%) or combined D (25%); 3,1 % with mild cognitive impairment (MCI), classified as F06.7 by the ICD-10 (International Classification of Diseases) and 6.2% with psychiatric disturbances. The most common BPSD were hallucinations, delusions, agitation, verbal and physical aggression. A paired t-test was applied to analyze data. There was a significant improvement with all 3 AA on NPI (mean NPI T(0)=27.50 vs. T(1)=12.13; t=7.49). An improvement was also observed on SVEBA (t=1.97), close to significance. Most people did not have any adverse effects; 5 patients (15.6%) had extrapyramidal symptoms and 1 (3.1%) showed ginecomasty, clinically so relevant to cause the interruption of the treatment. The profile of safety and efficacy described on the whole sample was confirmed when it was subdivided according to kind of drug, illness severity and presence/absence of CVRF. In a large sample of the "real" subjects attending a geriatric service for dementia, the accurate selection of patients treatable with AA leads to identification of a population with a negligible rate of adverse effects in presence of a high rate of efficacy with respect not only to BPSD but also to cognitive and functional domains.     

Donepezil for the treatment of behavioral disturbances in Alzheimer's disease: a 6-month open trial

Behavioral and psychological signs of dementia (BPSD) are common clinical characteristics of Alzheimer's disease (AD). They result in patient and caregivers distress, decreased quality of life and placement in nursing homes. Treatment of BPSD with antidepressant and antipsychotic medications is not without complications and serious adverse effects. The acetylcholinesterase inhibitors (AChEI) show preliminary promise as psychotropic agents possibly able to improve BPSD in AD patients. The present study aimed to evaluate the effect of donepezil (an AChEI) as an only treatment for AD patients with BPSD. Ten consecutive AD patients hospitalized at a psychogeriatric ward due to BPSD were treated with donepezil for 24 weeks. Effect was measured using the NeuroPsychiatric Inventory (NPI). Significant reduction in the presence of delusions, irritability/lability and disinhibition were achieved after 24 weeks of donepezil treatment. This was accompanied by reduction in caregivers distress. The drug was well tolerated and all patients completed the study. Our findings complement the preliminary data that donepezil as well as other AChEIs are promising candidates for further study as psychotropic agents positively affecting BPSD in AD patients.     

A systematic review of the use of aromatherapy in treatment of behavioral problems in dementia

We aimed to fill the literature gap by identifying the clinical benefits of aromatherapy in older adults with dementia, and its efficacy in reducing behavioral and psychological symptoms of dementia (BPSD) based on available randomized controlled trials (RCT). A systematic review of 11 clinical trials shortlisted from electronic databases from 1995 to 2011 was carried out. The RCT showed that aromatherapy had positive effects on reduction of BPSD, improvement in cognitive functions, increasing quality of life, enhancing independence of activities of daily living and so on. However, adverse effects were noted in some studies. Limitations on methodology are discussed and suggestions on directions of further studies are made. It is recommended that aromatherapy shows the potential to be applied as a therapeutic and safe complementary and alternative therapy for the management of BPSD on more evidence collected from better designed RCT. Geriatr Gerontol Int 2012; 12: 372–382.     

Psychobehavioral disorders in severe dementia

Behavioral and psychological symptoms of dementia (BPSD) are not included in the diagnostic criteria for dementia or in the assessment tools for grading its severity. However, they constitute a major part of the caregivers' burden and the main cause for institutionalization. They are, for one part, the direct consequence of the brain lesions, but, for another part, they result from the psychological reactions of the patients to their cognitive deficits or their relational difficulties with their family or carers. Despite speech disorder and mind disruption, patients with severe dementia still have a psychic and relational life, which is expressed through BPSD. Many BPSD are of short duration and can be improved by a better understanding, psychological and behavioral approach. However, psychotropic drugs are often useful or necessary, but, due to the frailty of the patients with severe dementia, their use should be very cautious.     

Risk factors and characteristics of the recurrence of behavioral and psychological symptoms of Alzheimer's disease

BackgroundThere is limited data on the risk factors and characteristics of the recurrence of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD).MethodsOne hundred and two AD patients complaining of BPSD were followed-up for 12 months after being well controlled. Potential risk factors for the recurrence of BPSD were evaluated. The severity of BPSD was measured using the Neuropsychiatric Inventory (NPI). NPI syndromes were categorized into affective impairments, psychotic symptoms, and lack of control disorders. Characteristics of the recurrent BPSD were compared with those of the former onset.ResultsForty-five of the patients presented recurrent BPSD within 12 months. Risk factors of recurrence included change of environment (RR = 5.42, p < 0.001), failure to maintain antipsychotic medication (RR = 3.13, p < 0.001), and high NPI score (RR = 1.06, p = 0.023) at the former onset. Both the number of symptoms and the affective subscores were correlated (r = 0.93, p = 0.011; r = 0.79, p = 0.016, respectively) and showed no significant difference between the two adjacent onsets of BPSD. The NPI total score (18.29 ± 2.06 vs. 20.80 ± 3.78, p = 0.031) and the psychotic subscore (6.49 ± 1.80 vs. 7.73 ± 1.92, p = 0.033) were significantly lower in the recurrent onset than those in the former and the two values showed no significant correlation between the two onsets. Subscores of lack of control of the two onsets were neither correlated nor different statistically from each other.ConclusionChange of environment, failure to maintain antipsychotic medication, and high NPI score at the former onset are risk factors for the recurrence of BPSD. Profiles of two onsets in the same patient are not always the same. The severity of BPSD and its psychotic symptoms show a tendency to ameliorate with the progression of AD. Affective impairments appear to be consistent. Lack of control disorders may be variable.     

Drug treatment of Alzheimer's disease

Drugs may be part of the treatment for Alzheimer's disease. Drug treatment can be divided into two categories: treatment to improve cognitive function and treatment to improve abnormal behaviors. There are at least 16 new drugs undergoing evaluation that may improve cognitive function. Some of these drugs are intended to augment acetylcholine neurotransmitter function. Others are nootropics that affect neuron metabolism with little effect elsewhere. A third major category is drugs that affect brain vasculature. A miscellaneous group includes drugs aimed at modifying other defects found in Alzheimer's disease. Drugs to affect behavior have been available for some time. These include neuroleptics, anxiolytics, and antirage drugs. Use of all these drugs has been controversial. Recent federal legislation and guidelines affect their use in nursing homes. Specific indications for neuroleptics are psychotic features and agitation. Dosage for patients with dementia is different than for other psychotic patients. There is no consensus on the use of other psychoactive medications.