Disturbances In Alzheimer's Disease Research Articles

Brainstem morphological changes in Alzheimer's disease.

As brainstem nuclei are interconnected with several cortical structures and regulate several autonomic, cognitive, and behavioral functions, it might be important to place the brainstem within an important pathologic core in the progression of Alzheimer's disease (AD). Although there have been several postmortem studies reporting neuropathological alterations of the brainstem in AD, there has been no in-vivo structural neuroimaging study of the brainstem in the patients with AD. The aim of this study was to investigate differences in the brainstem volume and shape between patients with AD and elderly normal controls. Fifty AD patients (the Clinical Dementia Rating Scale ≥ 1) and 50 normal controls were recruited, and the brainstem volumes and deformations were compared between the AD and the controls. Patients with AD showed significant total volume [(mean ± SD) 21007 ± 1640 mm] reduction in the brainstem compared with the controls [(mean ± SD) 22530 ± 1750 mm] (P<0.001). In addition, AD patients showed significant brainstem deformations in the upper posterior brainstem corresponding to the midbrain compared with the healthy individuals (false discovery rate corrected P<0.05). This study is the first to explore brainstem volume change and deformations in AD. These structural changes in the midbrain areas might be at the core of the underlying neurobiological mechanisms of brainstem dysfunction with relevance to their various cognitive and behavioral symptoms such as memory impairment, sleep, and emotional disturbance in AD. However, further longitudinal studies might be needed to confirm these findings.

Pin1 promotes degradation of Smad proteins and their interaction with phosphorylated tau in Alzheimer's disease.

Neurodegeneration in Alzheimer's disease (AD) is characterized by pathological protein aggregates and inadequate activation of cell cycle regulating proteins. Recently, Smad proteins were identified to control the expression of AD relevant proteins such as APP, CDK4 and CDK inhibitors, both critical regulators of cell cycle activation. This might indicate a central role for Smads in AD pathology where they show a substantial deficiency and disturbed subcellular distribution in neurones. Still, the mechanisms driving relocation and decrease of neuronal Smad in AD are not well understood. However, Pin1, a peptidyl-prolyl-cis/trans-isomerase, which allows isomerization of tau protein, was recently identified also controlling the fate of Smads. Here we analyse a possible role of Pin1 for Smad disturbances in AD. Multiple immunofluorescence labelling and confocal laser-scanning microscopy were performed to examine the localization of Smad and Pin1 in human control and AD hippocampi. Ectopic Pin1 expression in neuronal cell cultures combined with Western blot analysis and immunoprecipitation allowed studying Smad level and subcellular distribution. Luciferase reporter assays, electromobility shift, RNAi-technique and qRT-PCR revealed a potential transcriptional impact of Smad on Pin1 promoter. We report on a colocalization of phosphorylated Smad in AD with Pin1. Pin1 does not only affect Smad phosphorylation and stability but also regulates subcellular localization of Smad2 and supports its binding to phosphorylated tau protein. Smads, in turn, exert a negative feed-back regulation on Pin1. Our data suggest both Smad proteins and Pin1 to be elements of a vicious circle with potential pathogenetic significance in AD.

Sleep continuity scale in Alzheimer’s disease (SCADS): application in daily clinical practice in an Italian center for dementia

Sleep disorders can occur in many neurodegenerative disorders; in a previous paper we constructed a scale investigating sleep discontinuity/fragmentation with the aim to obtain a rapidly and easily administered tool suitable for early identification and longitudinal monitoring of sleep disturbances in Alzheimer's disease (AD). We introduced this instrument in the daily clinical practice in a center for dementia; here we present the results of our experience. Two hundred and sixteen AD outpatients referred to the Alzheimer's Disease Assessment Unit at the IRCCS C. Mondino National Neurological Institute, Pavia, Italy, in the period October 2012 to March 2014 were administered the scale. The questionnaire global score was correlated with measures of cognitive, functional and behavioral impairment; a significant association was found with Mini-Mental State (p = 0.005), Activities of Daily Living (p = 0.01), Neuropsychiatric Inventory (p = 0.01) and Clinical Dementia Rating (p = 0.0005). The present data indicate that the previously validated questionnaire proves to be a suitable, rapid and easy to use tool in investigating sleep quality in AD in daily clinical practice. An early identification and longitudinal monitoring of sleep disturbances in AD may improve pharmacological and non-pharmacological interventions.

Effect of a non-pharmacological intervention, Voix d’Or®, on behavior disturbances in Alzheimer disease and associated disorders

An innovative non-pharmacological intervention called Voix d'Or(®) (Golden Voice) was proposed in the Cognitive behavioral unit (CBU) of the Memory center at the Hospices civils in Lyon. Voix d'Or(®) offers eight sound activities disseminated via an audio device based on different approaches sociotherapeutic (music therapy, reminiscence, relaxation, reorientation in reality). The aim of this study was to test the effects of the Voix d'Or(®) program on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease hospitalized in the CBU. Twenty four patients with agitation and/or apathy and/or anxiety and/or depression were included. Patients were randomly selected in the intervention group exposed to Voix d'Or versus a control group exposed to usual occupational activities. Patients were assessed before (T0) and after (T1) the intervention period. Several variables were measured: frequency and severity of behavioral disorders, anxiety, depression, agitation and apathy. A significant improvement of anxiety level between T0 and T1was observed in the group with Voix d'Or(®) compared to the control group. This study suggests that this non-pharmacological intervention may be beneficial on anxiety in patients with Alzheimer's disease.

PRND 3′UTR polymorphism may be associated with behavioral disturbances in Alzheimer disease

The etiology of behavioral and psychological symptoms of dementia (BPSD) is complex, including putative biological, psychological, social and environmental factors. Recent years have witnessed accumulation of data on the association between genetic factors and behavioral abnormalities in Alzheimer disease (AD). In this research paper, our aim is to evaluate the association between the APOE, CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive impairment (MCI). We studied 99 patients with AD and 48 subjects with MCI. The presence and profile of BPSD were evaluated at baseline and prospectively with the Neuropsychiatric Inventory (NPI). Patients were dichotomized into those having ever experienced a particular symptom and those who did not over the whole disease period. Genotyping was performed using previously described standard protocols. The prevalence of comorbid behavioral symptoms and the overall level of behavioral burden were significantly greater in AD compared with the MCI group. In AD patients, carrier status of the T allele of the 3′UTR (untranslated region) PRND polymorphism was associated with an increased cumulative behavioral load and an elevated risk for delusions, anxiety, agitation/aggression, apathy and irritability/emotional ability. Among MCI subjects, APOE ε4 carriers demonstrated a reduced risk for nighttime behavior change. No other statistically significant genotype-phenotype correlations were observed, including the APOE, CYP46 and PRNP genes. A precise estimation of the exact significance of particular polymorphisms in BPSD etiology requires future studies on large populations.

Incidence and predictive factors of depressive symptoms in Alzheimer's disease: the REAL.FR study.

Many patients develop psychiatric and behavioral disturbances in the course of Alzheimer's disease (AD). Among these disturbances, depressive symptoms are frequent and affect nearly 40% of patients. The natural history and course of such symptoms in AD, and in particular the predictive factors, are little known. We studied the incidence and risk factors for the development of the first depressive symptoms in AD. Multicenter prospective study. Three hundred twelve AD patients from the French Network on AD (REAL.FR) without depression and without antidepressant treatment at baseline were followed up and assessed every 6 months for 4 years. During follow-up, all events occurring between two visits were carefully recorded. We used the Neuropsychiatric Inventory (NPI) for comprehensive evaluation of behavioral and psychological symptoms and depressive symptoms in particular. A multivariate analysis was performed using a backward stepwise Cox proportional hazards model. The incidence of depressive symptoms was 17.45% person/years, 95%CI (13.88-21.02). Among non-time dependent variables, duration of disease (RR=0.51; 95%CI: 0.30-0.85, p=0.0102) and the number of comorbid conditions (RR=0.45; 95%CI: 0.24-0.83, p=0.0115) were protective factors against the development of depressive symptoms. Agitation/aggression (RR=1.96; 95%CI: 1.19-3.23, p=0.0078) and sleep disturbances (RR=2.65; 95%CI: 1.40-5.00, p=0.0026) were time-dependent variables predictive of depressive symptoms. Better knowledge of predictive factors of mood disturbances in AD will enable clinicians to set up appropriate management of their patients. As published longitudinal studies are few, further works should be carried out to improve knowledge of the pattern and course of depression and depressive symptoms in AD.

Automatic video monitoring system for assessment of Alzheimer’s Disease symptoms

In order to fully capture the complexity of the behavioural, functioning and cognitive disturbances in Alzheimer Disease (AD) and related disorders information and communication techniques (ICT), could be of interest. This article presents using 3 clinical cases the feasibility results of an automatic video monitoring system aiming to assess subjects involved in a clinical scenario. The study was conducted in an observation room equipped with everyday objects for use in activities of daily living. The overall aim of the clinical scenario was to enable the participants to undertake a set of daily tasks that could realistically be achieved in the setting of the observation room. The scenario was divided in three steps covering basic to more complex activities: (1) Directed activities, (2) Semi-directed activities, (3) Undirected (“free”) activities. The assessment of each participant of the study was done with an automatic video monitoring system composed of a vision component and an event recognition component. The feasibility study involved three participants: two AD patients and one elderly control participant. The first result of the study was to demonstrate the feasibility of this new assessment method from both the patient and the technical points of view. During the first step the control participant performed all these activities faster than the two AD participants. During the second step of the scenario AD participants were not able to follow the correct order of the tasks and even omitted some of them. Finally during the last step of the scenario devoted to free activities the control participant chose one of the proposed activities (reading) and undertook this activity for almost the entire duration. In contrast, the two AD participants had more difficulties choosing one of the suggested activities and were not able to undertake any one activity in a sustained manner. The automatic video monitoring system presented here analyzes human behaviours and looks for changes in activity through the detection of the presence of people and their movements in real time. Once the technique has been standardized, it could significantly enhance the assessment of AD patients in both clinical and clinical trial settings as well as providing further information regarding patient frailty that could enhance their safety and ease caregiver burden.

Circadian Clock Gene Polymorphisms and Sleep–Wake Disturbance in Alzheimer Disease

One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes. One week of ad libitum ambulatory sleep data collection. At-home collection of sleep data and in-laboratory questionnaire. Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set. Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined. Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance. It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

Neuron Specific Toxicity of Oligomeric Amyloid-β: Role for JUN-Kinase and Oxidative Stress

Recent studies have demonstrated a potential role for oligomeric forms of amyloid-β (Aβ) in the pathogenesis of Alzheimer's disease (AD), although it remains unclear which aspects of AD may be mediated by oligomeric Aβ. In the present study, we found that primary cultures of rat cortical neurons exhibit a dose-dependent increase in cell death following Aβ oligomer administration, while primary cultures of astrocytes exhibited no overt toxicity with even the highest concentrations of oligomer treatment. Neither cell type exhibited toxicity when treated by equal concentrations of monomeric Aβ. The neuron death induced by oligomer treatment was associated with an increase in reactive oxygen species (ROS), altered expression of mitochondrial fission and fusion proteins, and JUN kinase activation. Pharmacological inhibition of JUN kinase ameliorated oligomeric Aβ toxicity in neurons. These data indicate that oligomeric Aβ is sufficient to selectively induce toxicity in neurons, but not astrocytes, with neuron death occurring in a JUN kinase-dependent manner. Additionally, these observations implicate a role for oligomeric Aβ as a contributor to neuronal oxidative stress and mitochondrial disturbances in AD.

Non-pharmacologic management of sleep disturbance in Alzheimer's disease.

Sleep and wake in Alzheimer's disease (AD) are often fragmented as manifested by bouts of wakefulness at night and napping during the day. Management of sleep disturbances in AD is important because of their negative impact on both patients and caregivers. Pharmacological treatments, mainly sedative-hypnotics and antipsychotics, are often used but can be associated with significant adverse effects. Non-pharmacological treatments represent a beneficial alternative approach to the management of sleep disturbances in AD since they are associated with fewer adverse effects and their efficacy can be sustained after treatment has been completed. The aim of this article is to review non-pharmacological treatments, such as sleep hygiene, sleep restriction therapy (SRT), cognitive behavioral therapy (CBT), light therapy, and continuous positive airway pressure (CPAP), for the management of sleep/wake disturbances in AD.

Sleep disturbances in Alzheimer's disease and other dementias

Sleep in dementias has been mainly studied in Alzheimer disease (AD). Sleep disturbances are found in 25 to 35% of subjects with AD. Subjective and objective disturbances are described. Long nocturnal awakenings disrupt sleep; total sleep time and sleep efficiency are reduced. Slow wave sleep is decreased and sometimes disappears. REM sleep percentage is also reduced and at a later stage of the disease, REM latency is increased. Sleep fragmentation can be associated with excessive daytime napping and sleepiness, and with other behavioral symptoms such as the sundowning syndrome and nocturnal agitation. Sleep abnormalities closely parallel the level of severity of dementia. The rest/activity ratio and the sleep-wake rhythms are more and more disturbed; the phase delay of the temperature rhythm is associated with the severity of the sundowning syndrome. Sleep disturbances and behavioral symptoms are the main reasons to institutionalize the patient. Sleep disturbances are related to multiple factors. Pathophysiological changes resulting of the disease itself, such as damage to the cholinergic pathways and to the circadian pacemaker in the suprachiasmatic nucleus, contribute to sleep changes in AD. Associated medical and psychiatric illness and their different treatments as well as environmental factors also induced sleep disturbances. Sleep-disordered breathing is a highly prevalent condition in AD patients and restless leg syndrome may account for nocturnal agitation. In Parkinson and in Lewy body dementias, sleep disturbances are more severe than in DA and REM sleep behavior disorder can precede by several years these diseases. Sleep attacks and sleepiness are very frequent in Parkinson disease. Specific etiologies should drive specific treatment. Several non pharmacologic treatments are usually associated to treat sleep disturbances in AD: information, increased daytime physical, social activities to minimize daytime naps and exposure to bright light. Some studies found advantages to associate melatonin in the evening.

Neurochemical basis for symptomatic treatment of Alzheimer's disease

Neuron and synapse loss together with neurotransmitter dysfunction have, along with Abeta deposition and neurofibrillary tangles, been recognized as hallmarks of Alzheimer's disease (AD). Furthermore, clinical and preclinical studies point to neuronal loss and associated neurochemical alterations of several transmitter systems as a main factor underlying both cognitive and neuropsychiatric symptoms. Treatment for the cognitive decline in AD, based on early findings of a cholinergic deficit, has been in the clinic for more than a decade but provides only modest benefit in most patients. Therefore there is still considerable scope for new treatments that demonstrate greater efficacy against cognitive dysfunction in spite of the fact that the mainstays of current treatments, the cholinesterase inhibitors Aricept, Exelon and Reminyl (Razadyne) will become generic over the next few years. However, the most important area for drug development is for the treatment of behavioural disturbance in AD since many existing treatments have limited efficacy and have potentially life-threatening side effects. This review examines the neurochemical underpinning of both cognitive and neuropsychiatric symptoms in dementia and provides some basis for rational drug development.

The Neuropsychiatric Inventory Scores Change Across the Mini Mental State Examination Ranges in Patients With Alzheimer's Disease: A Multicenter Study in Turkey

To investigate neuropsychiatric manifestations in patients at various stages of Alzheimer's disease (AD). Several earlier studies reported high prevalence of neuropsychiatric symptoms in patients with AD; to date, no such study has been conducted in Turkey. We evaluated 217 patients with AD from 18 referral centers across Turkey using a web-based dementia data registry. The Mini Mental State Examination and the Neuropsychiatric Inventory (NPI) were used to evaluate the global cognitive function, and assessment of neuropsychiatric symptoms, respectively. We classified the patients into mild, moderate, and severe stages on the basis of their Mini Mental State Examination scores. We assessed group differences and correlations between the degree of AD severity and NPI values. The highest NPI scores were seen in patients with severe AD. The mean composite scores for apathy, anxiety, and depression were the highest. The prevalence of any behavioral symptom was 86%. There was no difference in the behavioral domain between the groups or between the referral centers. Moderate correlation was found between the severity of AD and the total NPI score. The caregivers' NPI distress scores varied among referral centers. The prevalence of behavioral disturbance in AD is high and similar to earlier studies, yet regional differences are seen in caregivers' reactions to behavioral symptoms.

Does EEG (visual and quantitative) reflect mental impairment in subcortical vascular dementia?

The aim of this study was to determine if the results of visual and quantitative EEG (QEEG) parameters reveal a correlation with mental impairment in subcortical vascular dementia (SVD), one of the most frequent causes of cognitive impairment in the elderly. In SVD, like in Alzheimer's disease disturbances were found in cholinergic transmission. The cholinergic deficit as manifested in changes of synaptic potentials is reflected in EEG signals. Material 31 patients with probable SVD (according to NINCDS-AIREN and T. Erkinjuntii's criteria) and mean age 72.3 yrs;(M—43%, F—57%) and 14 healthy control subjects with mean age of 72.3 yrs (M—57%, F—43%). According to the Mini Mental Scale Examination (MMSE) the SVD group was divided into two subgroups with mild and moderate dementia, their EEGs being recorded with a Medelec and Neuroscan 4.2 system. Visual EEG findings were classified with the use of eight-degree scale of pathological changes by the presence of slow waves. Then QEEGs were made. The following parameters were calculated: alpha/slow wave power ratios, the mean wave frequency in all and in some selected derivations. Results A significant difference was found between QEEGs in SVD subgroups with mild and moderate dementia ( p < 0.05), but there was no significant difference between visual EEGs. A significant correlation between QEEG parameters such as alpha/slow wave ratio or mean wave frequency and mental impairment (according to MMSE results) was found ( p < 0.001), but there was no significant correlation between degree of EEG abnormalities in visual analysis and MMSE results. Conclusion Only QEEGs are correlated with mental impairment in SVD. Visual EEG technique as a less precise tool does not reflect the mental impairment in SVD due to cholinergic deficit.

Genetically Increased Risk of Sleep Disruption in Alzheimer's Disease

To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD). A case-control association analysis. Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A). Patients with AD diagnosed according to standard criteria. Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods. Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype. We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.

Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the “master clock”

The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hbeta1-adrenergic receptor (hbeta1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock genes was lost as well as the correlation between hPer1 and hbeta1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock gene changes and underlie the circadian rhythm disturbances in AD.

Effects of Cholinesterase Inhibitors on Behavioural Disturbances in Alzheimer???s Disease

Behavioural disturbances, also termed neuropsychiatric symptoms, are a frequent clinical feature of dementia in Alzheimer's disease (AD). Many AD patients receive treatment with cholinesterase inhibitors (ChEIs). This review examines the evidence for behavioural effects of the four ChEIs that have been approved for the treatment of mild to moderate AD. A systematic search of the MEDLINE and EMBASE databases and the Cochrane Library was conducted to identify clinical trials that had a randomised, placebo-controlled design. Studies were included in this review if they enrolled patients who had received a diagnosis of probable AD, involved at least one ChEI, and used an appropriate instrument for the assessment of behavioural disturbances. Fourteen studies that matched the selection criteria were identified in the literature. A statistically significant difference between active treatment and placebo with regard to behavioural symptoms was observed in three of the 14 studies. Treatment effects varied between 2.0 and 6.2 points on the Neuropsychiatric Inventory. ChEIs have moderate effects when used as a blanket treatment for the cluster of behavioural disturbances in AD. With regard to the limitations of the available trials, and in view of the risks that are associated with the use of atypical antipsychotics, the potential of ChEIs for the management of specific neuropsychiatric symptoms in patients with AD should be explored in further studies.

Treatment of behavioural, cognitive and circadian rest-activity cycle disturbances in Alzheimer's disease: haloperidol vs. quetiapine

This 5-wk, open-label, comparative study investigated the effects of quetiapine and haloperidol on behavioural, cognitive and circadian rest-activity cycle disturbances in patients with Alzheimer's disease (AD). Out of a total of 30 patients enrolled in the study, there were 22 completers, 11 in the quetiapine group (mean age 81.9+/-1.8 yr, mean baseline MMSE 19.9+/-1.3, mean dose 125 mg) and 11 in the haloperidol group (mean age 82.3+/-2.5 yr, mean baseline MMSE 18.1+/-1.3, mean dose 1.9 mg). As shown in the Neuropsychiatric Inventory, both medications reduced delusion and agitation, whereas quetiapine additionally improved depression and anxiety. Haloperidol worsened aberrant motor behaviour and caused extrapyramidal symptoms. In the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery which assessed cognitive parameters, quetiapine improved word recall; significant interaction terms revealed differences between quetiapine and haloperidol in word-list memory and constructional praxis. According to the Nurses' Observation Scale for Geriatric Patients (NOSGER) quetiapine improved instrumental activities of daily living. Actimetry documented the circadian rest-activity cycle before and after treatment. Sleep analysis revealed that patients receiving quetiapine had shorter wake bouts during the night, whereas patients receiving haloperidol had fewer though longer immobile phases. The study provides evidence that quetiapine at a moderate dose may be efficacious in treating behavioural disturbances in AD, with better tolerability than haloperidol.

Sleep disturbance in mild to moderate Alzheimer's disease

Background and purpose To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. Patients and methods Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. Results The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD ‘aggressiveness’ ( P=0.009) and ‘global rating’ ( P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. Conclusions Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.

P.5.029 Characteristic pattern of platelet phospholipases A2 and D disturbances in Alzheimer's disease

P.5.029 Characteristic pattern of platelet phospholipases A2 and D disturbances in Alzheimer's disease