Group and individual cognitive therapies in Alzheimer's disease: the ETNA3 randomized trial.

BACKGROUND: Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care. METHODS: This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization. RESULTS: No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced. CONCLUSIONS: These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.

Apathy in Neurodegenerative Diseases: Recommendations on the Design of Clinical Trials.

Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical trial setting due to practical and conceptual barriers. Principal challenges include a paucity of data regarding apathy in these disorders, an absence of established diagnostic criteria, the presence of confounding factors (eg, coexisting depression), use of concomitant medications, and an absence of a gold-standard apathy assessment scale. Based on a literature search and ongoing collaboration among the authors, we present recommendations for the design of future clinical trials of apathy, suggesting Alzheimer disease and Parkinson disease as models with relevance across a wider array of neuropsychiatric disorders. Recommendations address clarification of the targeted study population (apathy diagnosis and severity at baseline), confounding factors (mood/cognition, behavior, and treatment), outcome measures, study duration, use of comparators and considerations around environment, and the role of the caregiver and patient assent. This review contributes to the search for an optimal approach to study treatment of apathy in neuropsychiatric disorders.

Phenotyping apathy in individuals with Alzheimer disease using functional principal component analysis.

OBJECTIVES: To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD). DESIGN: Examination of ad libitum 24-hour ambulatory gross motor activity patterns. SETTING: Community-dwelling, outpatient. PARTICIPANTS: Ninety-two individuals with AD, 35 of whom had apathy. MEASUREMENTS: Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA). RESULTS: Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test). CONCLUSIONS: There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

Validation of the Brazilian version of the apathy inventory.

BACKGROUND: Apathy is a frequent neuropsychiatric condition in neurodegenerative disorders, depression, and often in mild cognitive impairment. The Apathy Inventory (AI) is a reliable instrument for improving the accuracy of the apathy diagnosis. The aim was to establish the validity of the Apathy Inventory for the Brazilian community. METHODS: We established the concurrent validity, internal consistency, inter-rater reliability, and the sensitivity and specificity of AI for the Brazilian community in a cohort of 175 individuals with Alzheimer's disease, Parkinson's disease, depression, mild cognitive impairment, and healthy controls. The three dimensions of the AI (emotional blunting, lack of initiative, and lack of interest) were compared with the Apathy domain of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C) in an independent scheme. RESULTS: The analyses demonstrated high correlation coefficients in AI's individual dimensions and in AI-total score (F = 0.965). Concerning the NPI-C/Apathy domain, intra-class correlation coefficients were also high (F = 0.977). Concurrent validity was high according to both raters on AI dimensions × NPI-C/Apathy domain and regarding total score (rater 1: rho = 0.956 vs. rater 2: rho = 0.970). The internal consistency of the AI was also high concerning the AI's individual dimensions and total score (rater 1: 0.945 vs. rater 2: 0.958). CONCLUSION: We observed high internal consistency, high concurrent validity, and inter-rater reliability of the Apathy Inventory. In addition, we found that its sensitivity and specificity were high. We suggest that the Brazilian version of the Apathy Inventory would be an appropriate instrument to identify the apathy syndrome in Brazilian patients.

Decreased daytime motor activity associated with apathy in Alzheimer disease: an actigraphic study.

OBJECTIVE: Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy. METHODS: One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups. RESULTS: Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Examination = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Examination = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups. CONCLUSIONS: Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

AMPA workshop on challenges faced by investigators conducting Alzheimer's disease clinical trials.

The recruitment and retention of patients are among the greatest challenges currently being faced by researchers who conduct Alzheimer's disease (AD) clinical trials. To discuss these challenges and other major issues associated with clinical research in AD, an international workshop was organized by the Association Monégasque pour la recherche sur la Maladie d'Alzheimer at Monte Carlo, Monaco, in February 2010, with the participation of leading research experts in the field of Alzheimer's. Key topics discussed were as follows: (1) the selection, recruitment, and retention of clinical trial subjects; (2) international co-operation among researchers; and (3) patient rights and informed consent for participants in clinical trials. This article highlights some of the challenges faced by investigators when conducting clinical trials in AD, and it also offers some recommendations aimed at overcoming these challenges.

Importance of lack of interest in patients with mild cognitive impairment.

OBJECTIVE: Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. DESIGN: Longitudinal study. SETTING: Fourteen French memory clinics. PARTICIPANTS: Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. MEASUREMENTS: The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. RESULTS: After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. CONCLUSIONS: Lack of interest, a mild behavioral sign, could be an indicator of potential decline in MCI patients and underlines the importance of checking the cognitive status of these patients.

Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium. Part II.

BACKGROUND/AIMS: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia. METHODS: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender. RESULTS: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes 'hyperactivity', 'psychosis', 'affective symptoms' and 'apathy' across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively. CONCLUSION: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity.

Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I.

BACKGROUND/AIMS: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). METHODS: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. RESULTS: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. CONCLUSION: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.

Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease: a one-year follow-up study.

OBJECTIVE: To evaluate the relation between apathy and development of dementia in patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI were enrolled. Apathy was assessed with the Apathy Inventory (IA). Neuropsychiatric evaluation also included the Goldberg anxiety scale and the Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point considered after a 1-year follow-up was the development of dementia of Alzheimer type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at least one symptom of apathy among the 216 included in analysis. After a 1-year follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13 (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients. At the 1-year follow-up, patients developing DAT had a significantly higher frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%). CONCLUSION: Taking into account that apathy is one of the most frequently observed neuropsychiatric symptoms in MCI and in DAT the present study suggests that patients with MCI and apathy should be more closely observed.

Associations between Neuropsychiatric Symptoms and Cerebral Amyloid Deposition in Cognitively Impaired Elderly People.

BACKGROUND: Neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD), affect the majority of patients with dementia, and result in a greater cognitive and functional impairment. OBJECTIVE: To investigate associations between BPSD and amyloid cerebral deposition as measured by 18F-Florbetapir-PET quantitative uptake in elderly subjects with and without cognitive impairment. METHODS: Participants with cognitive impairment [mild cognitive impairment (MCI) or Alzheimer's disease (AD)] and healthy controls (HC) from the ADNI cohort (Alzheimer Disease Neuroimaging Initiative) who underwent an 18F-florbetapir PET scan between May 2010 and March 2014 were included. Clinical assessments included the Clinical Dementia Rating, the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Freesurfer software was used to extract PET counts based on T1-based structural ROI (frontal, cingulate, parietal, and temporal). Spearman's partial correlation scores between BPSD severity and regional amyloid uptake were calculated. RESULTS: Data for 657 participants [age = 72.6 (7.19); MMSE = 27.4 (2.67)] were analyzed, including 230 HC [age = 73.1 (6.02); MMSE = 29 (1.21)], 308 MCI [age = 71.5 (7.44); MMSE = 28.0 (1.75)], and 119 AD subjects [age = 74.7 (8.05); MMSE = 23.1 (2.08)]. Considering all diagnostic groups together, positive significant correlations were found between anxiety and 18F-florbetapir uptake in the frontal (r = 0.102; p = 0.009), cingulate (r = 0.083; p = 0.034), and global cerebral uptake (r = 0.099; p = 0.011); between irritability and frontal (r = 0.089; p = 0.023), cingulate (r = 0.085; p = 0.030), parietal (r = 0.087; p = 0.025), and global cerebral uptake (r = 0.093; p = 0.017); in the MCI subgroup, between anxiety and frontal (r = 0.126; p = 0.03) and global uptake (r = 0.14; p = 0.013); in the AD subgroup, between irritability and parietal uptake (r = 0.201; p = 0.03). CONCLUSION: Anxiety and irritability are associated with greater amyloid deposition in the neurodegenerative process leading to AD.

Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer disease consortium.

Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer's disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient's lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer's Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.

'Kitchen and cooking,' a serious game for mild cognitive impairment and Alzheimer's disease: a pilot study.

Recently there has been a growing interest in employing serious games (SGs) for the assessment and rehabilitation of elderly people with mild cognitive impairment (MCI), Alzheimer's disease (AD), and related disorders. In the present study we examined the acceptability of 'Kitchen and cooking' - a SG developed in the context of the EU project VERVE (http://www.verveconsortium.eu/) - in these populations. In this game a cooking plot is employed to assess and stimulate executive functions (such as planning abilities) and praxis. The game is installed on a tablet, to be flexibly employed at home and in nursing homes. Twenty one elderly participants (9 MCI and 12 AD, including 14 outpatients and 7 patients living in nursing homes, as well as 11 apathetic and 10 non-apathetic) took part in a 1-month trail, including a clinical and neuropsychological assessment, and 4-week training where the participants were free to play as long as they wanted on a personal tablet. During the training, participants met once a week with a clinician in order to fill in self-report questionnaires assessing their overall game experience (including acceptability, motivation, and perceived emotions). The results of the self reports and of the data concerning game performance (e.g., time spent playing, number of errors, etc) confirm the overall acceptability of Kitchen and cooking for both patients with MCI and patients with AD and related disorders, and the utility to employ it for training purposes. Interestingly, the results confirm that the game is adapted also to apathetic patients.

Brain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors.

UNLABELLED: Transient cognitive and behavioral stabilization of patients with Alzheimer's disease (AD) is the main goal of long-term acetylcholinesterase inhibitor (AChEI) therapy, but response to treatment is variable and, indeed, only some of the patients are stabilized. This is usually assessed by means of clinical and neuropsychologic scales, whereas functional neuroimaging could allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. The aim of this study was to evaluate brain perfusion changes by SPECT in AD patients during chronic AChEI therapy in relation to their cognitive evolution. METHODS: Forty-seven consecutive outpatients with mild-to-moderate probable AD (as defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders [4th edition criteria] and a score of > or =15 on the Mini-Mental State Examination [MMSE]) were enrolled in 2 centers over a 1-y period and underwent SPECT with 99mTc-hexamethylpropyleneamine oxime at the time of enrollment (t(0)). All of them started AChEI therapy. Nine patients were lost at follow-up, and drugs were withdrawn from 3 patients. Of the remaining 35 patients, who received regular AChEI therapy (donepezil, 5 or 10 mg/d; rivastigmine, 6 or 9 mg/d) throughout the observation period, only the 31 patients receiving donepezil were considered to avoid the possible confounding effect of different drugs. The 31 patients completed the study and a second SPECT examination was performed 15.0 +/- 3.0 mo later (t(1)). They were divided into stabilized (17 patients) and nonstabilized (14 patients) subgroups on the basis of the minimum expected annual rate of decline of the MMSE score, derived from a meta-analysis of the literature. SPECT data were analyzed by means of statistical parametric mapping. RESULTS: At baseline, the stabilized and nonstabilized patients were comparable for age, sex distribution, education, MMSE scores, memory impairment (selective reminding test [SRT]), apolipoprotein E genotype, AChEI dose regimen, and SPECT findings. The SRT scores decreased significantly (P < 0.01) in the nonstabilized subgroup but not in the stabilized subgroup. No significant difference was found between the baseline and repeated SPECT data in the stabilized subgroup. In contrast, in the nonstabilized subgroup a significant perfusion reduction was found in the frontal, temporal, and parietal superficial cortex and in the occipital precuneus in the right hemisphere and in the frontal and mesial temporal cortex in the left hemisphere. On repeated SPECT, regional cerebral blood flow was significantly lower in a left frontal region in the nonstabilized group than in the stabilized group. CONCLUSION: The regional cerebral blood flow decreases in several cortical regions in AD patients with cognitive deterioration despite long-term AChEI therapy, similar to that observed in untreated patients, whereas it remains stable in AD patients with stabilized cognitive performance during therapy.

Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis.

Alzheimer's disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.

Actigraphic motor activity in mild cognitive impairment patients carrying out short functional activity tasks: comparison between mild cognitive impairment with and without depressive symptoms.

BACKGROUND: Individuals with mild cognitive impairment (MCI) may exhibit changes in motor activity in conducting their activities of daily living. Depression, one of the most frequent neuropsychiatric symptoms, might affect motor activity in MCI. OBJECTIVE: To assess motor activity in MCI subjects carrying out short functional activity tasks using ambulatory actigraphy. Secondly, we sought to investigate the influence of depressive symptoms on motor activity. METHODS: 20 MCI and 14 healthy subjects carried out a 30-minute standardized scenario while wearing a chest actigraph. The protocol consisted of directed activities (execution of motor tasks), semi-directed activities (execution of Instrumental Activities of Daily Living, IADL), and undirected 'free' activities. Several common assessment scales (GDS, MADRS, and NPI) were used to diagnose depression. RESULTS: MCI subjects had significantly reduced mean motor activity while carrying out directed and semi-directed activities, compared to healthy control subjects. No difference was found in motor activity between MCI subjects with or without depression. CONCLUSION: Actigraphic measurement of motor activity during the evaluation of IADLs and motor tasks is a potential objective tool in detecting early changes in MCI. Depressive symptoms seem not to be associated with motor activity in MCI subjects.

Recommendations for the use of Serious Games in people with Alzheimer's Disease, related disorders and frailty.

Alzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority.

Imaging correlates of apathy and depression in Parkinson's disease.

Though the core symptoms of Parkinson's disease (PD) are motor-related, a majority of patients also have neuropsychiatric symptoms concerning mood, behavior and cognition. Apathy and depression are considered among the most frequent ones, and have a negative impact on global functioning and quality of life. Recent neuroimaging studies have provided specific findings related with these symptoms. Depression in PD has been specifically associated with morphological and functional changes in prefrontal cortex, cingulate and thalamus, as with 5-HT transmission reduction in posterior cingulated and amygdala-hippocampus complex. Apathy has received less attention, but has been related with gray matter volume reductions or functional deficits in many regions, as anterior and posterior cingulate and dorsolateral or inferior frontal gyrus. Some of these deficits may be also related with a more pronounced reduction in striatal dopamine transmission. As neuroimaging studies give more arguments to the mechanisms of these symptoms, they also stimulate research for a better individualization of specific affective dimensions in Parkinson's disease.

Relationship between apathy and sleep disturbance in mild and moderate Alzheimer's disease: an actigraphic study.

Apathy is the most frequently reported neuropsychiatric symptom across all stages of Alzheimer's disease (AD). Both apathy and sleep disorders are known to have independent negative effects on the quality of life in individuals with AD. The aim of this study was to assess the relationship between apathy and sleep/wake patterns in individuals with AD using ambulatory actigraphy. One hundred and three non-institutionalized individuals with AD wore a wrist actigraph continuously over seven consecutive 24-h periods. Apathy was assessed using the Neuropsychiatric Inventory. Daytime mean motor activity (dMMA) was calculated from daytime wrist actigraphy data. Actigraphic parameters of sleep included total sleep time (TST), wake after sleep onset (WASO), time in bed (TIB), WASO normalized by TIB, sleep latency, and nighttime mean motor activity (nMMA). Among the 103 individuals with AD (aged 76.9 ± 7.2 years; MMSE = 21.4 ± 4.3), those with apathy had significantly lower dMMA, higher WASO (both raw and normalized), and spent more time in bed during the night than those without apathy. Sleep latency, nMMA and TST did not differ significantly between the two subgroups. To our knowledge, this study is the first to identify a relationship between apathy and sleep disturbance in those with mild or moderate AD: apathy was associated with increased TIB during the night and more WASO. These results suggest that AD patients with apathy have less consolidated nocturnal sleep than those without apathy.