Shoulder Joint Range of Motion Related to Dementia.

INTRODUCTION: Dementia is caused by various diseases, including Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLB). We often encounter patients with dementia who have limited shoulder joint range of motion (ROM), especially those with behavioral and psychological symptoms of dementia (BPSD). But the relationship between the diseases of dementia and restricted shoulder joint ROM is currently unclear. METHODS: We examined cognitive function and shoulder joint ROM in 234 new outpatients at 7 memory clinics in Japan. We assessed cognitive function using the Mini-Mental State Examination (MMSE) and Revised Hasegawa Dementia Scale (HDS-R) and BPSD using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Patients were categorized by dementia diagnosis (ADD, DLB, other dementia, and control). Right, left, and total shoulder joint ROM was assessed using validated the Japanese Orthopaedic Association (JOA) score. RESULTS: We found significant associations of lower right, left, and total shoulder joint ROM scores with male sex, advanced age, higher NPI-Q score, lower HDS-R, and MMSE scores. Little difference was found between right and left shoulder joint ROM scores. Restricted shoulder joint ROM was related to serial 7, verbal frequency domain scores on the HDS-R and repeat score on the MMSE. It was also related to the hallucinations, irritability/lability and nighttime disturbances scores on the NPI-Q. Furthermore, the dementia groups, especially the DLB group, showed worse shoulder joint ROM than the control group. CONCLUSIONS: Dementia was significantly related to restricted shoulder joint ROM. Maintaining communication and social interaction may help maintain shoulder joint ROM.

Application of the mild behavioral impairment checklist in Chinese patients with the behavioral variant of frontotemporal dementia.

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. RESULTS: The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. CONCLUSION: The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.

Difference of Cerebrospinal Fluid Biomarkers and Neuropsychiatric Symptoms Profiles among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient.

The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-ß42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer's Coordinating Center's Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-ß42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer's disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-ß at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aß-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aß-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer's patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.

BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study.

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.

Neuropsychiatric symptoms after moderate-to-severe traumatic brain injury in Vietnam: Assessment, prevalence, and impact on caregivers.

OBJECTIVE: Neuropsychiatric symptoms (NPSs) after moderate-to-severe traumatic brain injury (TBI) have been well documented in WEIRD (Western, educated, industrialized, rich, and democratic) populations. In non-WEIRD populations, such as Vietnam, however, patients with TBI clinically remain uninvestigated with potential neuropsychiatric disorders, limiting on-time critical interventions. This study aims to (1) adapt the Vietnamese Neuropsychiatric Inventory (V-NPI), (2) examine NPSs after moderate-to-severe TBI and (3) evaluate their impact on caregiver burden and well-being in Vietnam. METHOD: Caregivers of seventy-five patients with TBI completed the V-NPI, and other behavior, mood, and caregiver burden scales. RESULTS: Our findings demonstrated good internal consistency, convergent validity, and structural validity of the V-NPI. Caregivers reported that 78.7% of patients with TBI had at least three symptoms and 16.0% had more than seven. Behavioral and mood symptoms were more prevalent (ranging from 44.00% to 82.67% and from 46.67% to 66.67%, respectively) and severe in the TBI group. Importantly, NPSs in patients with TBI uniquely predicted 55.95% and 33.98% of caregiver burden and psychological well-being, respectively. CONCLUSION: This study reveals the first evidence for the presence and severity of NPSs after TBI in Vietnam, highlighting an urgent need for greater awareness and clinical assessment of these symptoms in clinical practice. The adapted V-NPI can serve as a useful tool to facilitate such assessments and interventions. In addition, given the significant impact of NPS on caregiver burden and well-being, psychosocial support for caregivers should be established.

Neuropsychiatric symptoms and their neural correlates in individuals with mild cognitive impairment.

OBJECTIVES: Neuropsychiatric symptoms are common in subjects with MCI and associated with higher risk of progression to AD. The cognitive and neuroanatomical correlates of neuropsychiatric symptoms in MCI have not been fully elucidated. In this study, we sought to evaluate the association between neuropsychiatric symptoms, cognitive function, regional tau deposition, and brain volumes in MCI subjects. METHODS: A total of 233 MCI and 305 healthy comparisons were selected from the ADNI-3 cohort. All the subjects underwent a comprehensive neuropsychological assessment, volumetric MR brain scan, and Flortaucipir PET for in vivo assessment of regional tau deposition. Prevalence of neuropsychiatric symptoms was evaluated by means of the NPI questionnaire. Multivariate analyses of variance were used to detect differences in cognitive and imaging markers in MCI subjects with and without neuropsychiatric symptoms. RESULTS: 61.4% MCI subjects showed at least one neuropsychiatric symptom, with the most prevalent ones being depression (26.1%), irritability (23.6%), and sleep disturbances (23.6%). There was a significant effect of neuropsychiatric symptoms on cognitive tests of frontal and executive functions. MCI subjects with neuropsychiatric symptoms showed reduced brain volumes in the orbitofrontal and posterior cingulate cortices, while no effects were detected on regional tau deposition. Posterior cingulate cortex volume was the only predictor of global neuropsychiatric burden in this MCI population. CONCLUSIONS: Neuropsychiatric symptoms occur early in the AD trajectory and are mainly related to defects of control executive abilities and to the reduction of gray matter volume in the orbitofrontal and posterior cingulate cortices. A better understanding of the cognitive and neuroanatomical mechanisms of neuropsychiatric symptoms in MCI could help develop more targeted and efficacious treatment alternatives.

Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project).

BACKGROUND: Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. OBJECTIVE: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. METHODS: A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. RESULTS: Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4-5, and stages GDS 6-7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). CONCLUSIONS: The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.

Neuropsychiatric outcomes and caregiver distress in primary progressive aphasia.

BACKGROUND: In this study, we aimed to outline the neuropsychiatric consequences of primary progressive aphasia (PPA) and to understand how neuropsychiatric symptomatology affects distress in caregivers. METHODS: The Neuropsychiatric Inventory (NPI) including the distress index (NPI-Distress) was used. Additional information about the caregiver burden was obtained using Zarit Burden Interview (ZBI). NPI, NPI-Distress, and ZBI data from 17 patients with a clinical diagnosis of PPA were compared with 10 stroke aphasia patients. Neuropsychiatric symptomatology was investigated based on three clusters; Mood, Frontal/Comportmental, and Psychotic/Disruptive. Additionally, the Activities of Daily Living Questionnaire (ADLQ) was used to outline the functional impairment. Twelve healthy controls were included to compare the neurocognitive test scores with PPA and stroke aphasia groups. RESULTS: A greater number of neuropsychiatric symptoms were observed in the PPA group compared to the stroke aphasia group. The number of symptoms in Mood, and Frontal/Comportmental clusters were greater than the number of symptoms in Psychotic/Disruptive clusters in the PPA group, whereas no significant relationship between the number of symptoms and symptom clusters was found in the stroke aphasia group. In the PPA group, a strong correlation was found between the NPI-Frequency × Severity scores and the NPI-Distress scores. Moreover, the NPI-Distress scores in the PPA group strongly correlated with the ZBI scores. Scores for anxiety, irritability/lability, and apathy had a stronger correlation with the NPI-Distress scores compared to the other NPI symptoms. The Communication subscale was the most impaired domain in the PPA group. Travel, and Employment and Recreation subscales showed greater functional impairment in the stroke aphasia group compared to the PPA group. CONCLUSIONS: Neuropsychiatric symptoms in PPA in our study were more frequent than previously reported. Furthermore, the distress index of the NPI was not only correlated with the severity of the neuropsychiatric symptoms but also reflected the overall burden on the caregivers in the PPA group.

Agitation in Cognitive Disorders: Use of the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS) to Evaluate International Psychogeriatric Association Definition.

OBJECTIVE: Consensus-based definition of agitation by the International Psychogeriatric Association (IPA) has not been evaluated in community-based samples who are not preselected for behavioral disturbances. Here, we use a well-characterized cohort of community-dwelling older adults with cognitive impairment to assess the IPA criteria associated with agitation to evaluate the construction of this diagnostic entity. METHODS: We used the National Alzheimer Coordinating Center Unified Data Set (NACC-UDS) to construct the IPA consensus-based provisional definition of agitation in cognitive impairment (N = 19,424). We used clinician diagnosis of agitation as a gold standard in those with mild cognitive impairment and dementia and used the Neuropsychiatric Inventory-Questionnaire to define agitation symptoms and standardized assessments of function (including the Functional Assessment Scale and Clinical Dementia Rating Scale Sum of Boxes) to assess "excess disability." We also examined patterns of psychiatric comorbidities to determine if they were consistent with IPA criteria. RESULTS: There was agreement between the selected NPI measure of agitation and clinician judgment (sensitivity = 0.79, specificity = 0.69, Cohen's Kappa = 0.304). More than 84% of those with clinician judgment of agitation and 74% of those meeting the scale-based definition of agitation demonstrated excess social/functional disability. Comorbid psychiatric symptoms were present in 38% of the sample without agitation and higher in those with agitation by either definition. CONCLUSION: Agitation ranges between 15% and 48% in those with cognitive impairment. The pattern of level of excess disability and the presence of comorbid psychiatric symptoms is consistent with the profile of published definitions.

Neuropsychiatric Inventory Questionnaire Associated with Cognitive Function, Age, and Duration of Education in Patients with Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common cognitive disease, and behavioral and psychological symptoms of dementia (BPSD) can place a heavy burden on families. The presence of these symptoms related to AD is commonly assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). This study sought to clarify the relationship between scores on the 12-domain NPI-Q and individual factors in patients with AD. METHODS: Participants were 218 new outpatients with AD at five memory clinics. Cognitive function was assessed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We examined which individual factors were associated with the total NPI-Q score and the number of domains. We also examined which domains were associated with the factors identified. RESULTS: A higher total NPI score was significantly associated with lower scores on both cognitive assessments and a longer duration of education. Exhibiting symptoms on a greater number of domains was significantly associated with lower scores on both cognitive assessments, longer duration of education, and advanced age. The nighttime disturbances domain was significantly associated with lower scores on both cognitive assessments and advanced age. The delusions domain was significantly associated with lower education. CONCLUSIONS: BPSD may appear more easily with reduced quality of life and ongoing dissatisfaction. Effective individualized services are important for patients with AD, and therefore, we should account for age, cognitive function, and duration of education in the services provided.

Managing Behavioral and Psychological Symptoms of Dementia (BPSD) in the Era of Boxed Warnings.

PURPOSE OF REVIEW: To provide a comprehensive overview on the evaluation and management of behavioral and psychological symptoms of dementia (BPSD) using evidence from literature. RECENT FINDINGS: Evidence indicates efficacy for some non-pharmacological techniques including education of caregivers and cognitive stimulation therapy and pharmacological agents like antidepressant and antipsychotics for the management of BPSD. The use of antipsychotics has generated controversy due to the recognition of their serious adverse effect profile including the risk of cerebrovascular adverse events and death. BPSD is associated with worsening of cognition and function among individuals with dementia, greater caregiver burden, more frequent institutionalization, overall poorer quality of life, and greater cost of caring for these individuals. Future management strategies for BPSD should include the use of technology for the provision of non-pharmacological interventions and the judicious use of cannabinoids and interventional procedures like ECT for the management of refractory symptoms.

Biweekly fluctuations of neuropsychiatric symptoms according to the Neuropsychiatric Inventory: Erratic symptoms or scores?

OBJECTIVES: This study investigates the stability of neuropsychiatric symptoms (NPS) assessed biweekly using the Neuropsychiatric Inventory (NPI) in a memory clinic population during a 6 week period. METHODS: Twenty-three spousal caregivers (mean [SD] age = 69.7 [8.8], 82.6% female) of 23 patients (43.5% had dementia) completed all assessments. The NPI was assessed four times during 6 weeks. We examined whether NPI domains were present during all four assessments, studied within-person variation for each NPI domain, and calculated Spearman's correlations between subsequent time-points. Furthermore, we associated repeated NPI assessments with repeated measures of caregiver burden to examine the clinical impact of changes in NPI scores over time. RESULTS: The course of NPS was highly irregular according to the NPI, with only 35.8% of the NPI domains that were present at baseline persisted during all 6 weeks. We observed large within-person variation in the presence of individual NPI domains (61.3%, range 37.5%-83.9%) and inconsistent correlations between NPI assessments (e.g., range rs  = 0.20-0.57 for agitation, range rs  = 0.29-0.59 for anxiety). Higher NPI total scores were related to higher caregiver burden (rs  = 0.60, p < 0.001), but changes in NPI total scores were unrelated to changes in caregiver burden (rs  = 0.16, p = 0.20). CONCLUSIONS: We observed strong fluctuations in NPI scores within very short time windows raising the question whether this represents erratic symptoms and/or scores. Further studies are needed to investigate the origins of these fluctuations.

Neuropsychiatric symptoms and subsyndromes in patients with different stages of dementia in primary care follow-up (NeDEM project): a cross-sectional study.

BACKGROUND: The objective was to describe the prevalence and intensity of neuropsychiatric symptoms (NPSs) isolated and grouped into subsyndromes in patients with dementia in primary care (PC) to analyse their distribution based on stages of dementia and the relationship between them and the intensity of symptoms. METHODS: Design: Cross-sectional study. SETTING AND POPULATION: Patients with dementia, not institutionalized, in a PC follow-up. VARIABLES: Sociodemographic and clinical variables. Assessment instruments: The frequency and intensity of NPSs were measured with the Neuropsychiatric Inventory (NPI), and the stages of dementia with the Global Deterioration Scale (GDS). STATISTICAL ANALYSIS: The number of NPSs per patient, the mean NPI value, and the prevalence and intensity of NPSs isolated and grouped into subsyndromes were calculated, as were their 95% confidence intervals (CIs). The analyses were performed on an overall basis and by GDS scores. To analyse the association between the NPI and GDS scores, multivariate analysis was performed with a generalized linear model. RESULTS: Overall, 98.4% (95% CI 94.5;99.8) of the patients presented some type of NPS, with an average of five symptoms per patient. The most frequent symptoms were apathy [69.8% (95% CI 61.1;77.5)], agitation [55.8% (95% CI 46.8;64.5)] and irritability [48.8% (95% CI 39.9;57.8)]. The more intense NPSs were apathy [NPI 3.2 (95% CI 2.5;3.8)] and agitation [NPI 3.2 (95% CI 2.5;4.0)]. For subsyndromes, hyperactivity predominated [86.0% (95% CI 78.8;91.5)], followed by apathy [77.5% (95% CI 69.3;84.4]). By phase of dementia, the most common isolated symptom was apathy (60.7-75.0%). Affective symptoms and irritability predominated in the initial stages, and psychotic symptoms predominated in advanced stages. The mean NPI score was 24.9 (95% CI 21.5;28.4) and increased from 15.6 (95% CI 8.2;23.1) for GDS 3 to 28.9 (95% CI 12.6;45.1) for GDS 7. Patients with in the most advanced stages of dementia presented an NPI score 7.6 (95% CI 6.8;8.3) points higher than the score for mild dementia with adjustment for the other variables. CONCLUSIONS: A high prevalence of NPSs was found among patients with dementia treated in PC. Symptoms change and increase in intensity as the disease progresses. Scales such as the NPI allow these symptoms to be identified, which may facilitate more stage-appropriate management.

The effects of caregiver characteristics on behavioral and psychological symptoms of dementia of patients with dementia.

OBJECTIVE: To determine the association between caregiver characteristics and behavioral and psychological symptoms of dementia (BPSD) in patients with dementia (PWD) in a Taiwanese community-dwelling population. METHODS: This cross-sectional study was conducted using the data of 190 patients with Alzheimer's disease/dementia and 190 informal matched caregivers in Taiwan. BPSD were examined using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Correlation and regression analyses were used to explore associations between caregiver characteristics and the presence, severity, and distress of NPI-Q items. RESULTS: Only spouse primary caregiver was positively associated with presence of delusions in PWD. Caregiver education was positively correlated to severity of hallucinations, agitation/aggression, and apathy/indifference in PWD, while child primary caregiver was positively related to severity of disinhibition in PWD but negatively related to severity of anxiety in PWD. Spouse primary caregiver was positively related to severity of anxiety and appetite/eating in PWD while sole primary caregiver was positively related to severity of anxiety and nighttime behaviors in PWD. Caregiver education was positively correlated to distress of agitation/aggression in caregivers while child primary caregiver was positively related to distress of disinhibition in caregivers. Spouse primary caregiver was positively related to distress of anxiety and appetite/eating in caregivers while spouse caregiver was positively related to distress of nighttime behaviors in caregivers. CONCLUSIONS: Caregiver education, child and spouse primary caregiver were relevant to severity of PWD and distress of caregivers of BPSD. It is suggested that healthcare professionals provide caregivers with proper individualized interventions based on these results to enhance caring quality.Key pointsCaregiver education was positively correlated to severity of hallucinations, agitation/aggression, and apathy/indifference, and distress of agitation/aggression.Child primary caregiver was positively related to severity and distress of disinhibition but negatively related to severity of anxiety.Spouse primary caregiver was positively related to severity and distress of anxiety and appetite/eating, and distress of nighttime behaviors.

Most families tend to realize progress of Alzheimer's disease when behavioural and psychological symptoms are obvious.

BACKGROUND: Alzheimer's disease (AD) is a common cognitive disease that can progress at an accelerating rate. Even with early diagnosis, the families might not recognize AD progressing unless behavioural and psychological symptoms of dementia (BPSD) develop. In many cases, discrepancies could exist between family-assessed AD stage and diagnosed AD stage. This study explored such discrepancies and potential clinical implications. METHODS: Participants were 161 new outpatients with AD or mild cognitive impairment at four memory clinics whose AD stage was diagnosed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We classified patients into four groups according to AD severity. Family members completed the Functional Assessment Staging (FAST) scale during an interview. We then assigned patients to three groups according to discrepancies between family-assessed and diagnosed AD stage. Families also completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), which assesses 12 neuropsychiatric domains, in order to examine the presence of BPSD in relation to AD stage. RESULTS: Most families (74%-80%) assessed patients as having milder AD than the diagnosed stage. NPI-Q scores and duration of education significantly affected discrepancies with HDS-R and MMSE scores. The NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance significantly affected family-assessed FAST. Families of patients with more years of education assessed the AD stage as more advanced than the diagnosed stage. Surprisingly, living together did not significantly affect the discrepancy. CONCLUSIONS: Most families assessed AD as milder than the clinically diagnosed AD stage. In addition, high NPI-Q scores and more years of school education significantly affected the discrepancy. Family-assessed FAST was significantly affected by the NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance. These results suggest that obvious BPSD are significant factors for Japanese families to recognize AD progress.

Don't Bother Trying, They Won't Do It! Effect of Responsive Behaviors on the Montessori Assessment System.

OBJECTIVES: The Montessori Assessment System (MAS) is an assessment tool that aims at assessing preserved abilities in persons with moderate to severe dementia and to serve as basis for person-centered interventions. As responsive behaviors are highly frequent in this population, we assessed their possible influence on the MAS administration and results. METHODS: 193 persons with a diagnosis of dementia in the moderate to severe stages living in nursing homes completed the MAS. Responsive behaviors were assessed by the Neuropsychiatric Inventory (NPI). RESULTS: The NPI scores were heterogeneous, but responsive behaviors were present for at least 5 NPI domains in more than 50% of the participants. While NPI scores had weak relationships with MAS completion time and total score, primarily for the hallucinations, euphoria, and aberrant motor behaviors domains, a large majority of the participants fully completed the MAS. CONCLUSIONS: The presence of responsive behaviors as assessed by the NPI does not limit MAS administration, despite minor influence on MAS score and completion time. CLINICAL IMPLICATIONS: The MAS may be applied to persons with moderate to severe dementia presenting responsive behaviors. Assessment of preserved abilities can greatly improve the design of person-centered care plans in this population.

Measuring Apathy in Alzheimer's Disease in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): A Comparison of Instruments.

BACKGROUND: Diagnostic criteria for apathy have been published but have yet to be evaluated in the context of clinical trials. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) operationalized the diagnostic criteria for apathy (DCA) into a clinician-rated questionnaire informed by interviews with the patient and caregiver. OBJECTIVE: The goal of the present study was to compare the classification of apathy using the DCA with that using the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale in ADMET 2. Comparisons between NPI-Apathy and Dementia Apathy Interview Rating (DAIR) scale, and DCA and DAIR were also explored. METHODS: ADMET 2 is a randomized, double-blind, placebo-controlled phase III trial examining the effects of 20 mg/day methylphenidate on symptoms of apathy over 6 months in patients with mild to moderate Alzheimer's disease (AD). Participants scoring at least 4 on the NPI-Apathy were recruited. This analysis focuses on cross-sectional correlations between baseline apathy scale scores using cross-tabulation. RESULTS: Of 180 participants, the median age was 76.5 years and they were predominantly white (92.8%) and male (66.1%). The mean (±standard deviation) scores were 7.7 ± 2.4 on the NPI-apathy, and 1.9 ± 0.5 on the DAIR. Of those with NPI-defined apathy, 169 (93.9%, 95% confidence interval [CI] 89.3%-96.9%) met DCA diagnostic criteria. The DCA and DAIR overlapped on apathy diagnosis for 169 participants (93.9%, 95% CI 89.3%-96.9%). CONCLUSION: The measurements used for the assessment of apathy in patients with AD had a high degree of overlap with the DCA. The NPI-apathy cut-off used to determine apathy in ADMET 2 selects those likely to meet DCA criteria.

Trajectories of depression symptoms over time differ by APOE4 genotype in older adults with type 2 diabetes.

OBJECTIVES: The APOE-ε4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-ε4 genotype in older adults with T2D. METHODS: Participants (n = 754 [13.1% APOE-ε4 carrier]s) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of ε4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). RESULTS: Participants' mean age was 71.37 (SD = 4.5); 38.2% female. In comparison to non-carriers, APOE-ε4 carriers had lower mean GDS scores (ß = -0.46, p = 0.018) and lower NPI-depression scores (ß = -0.170, p = 0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (ß = -0.005, p = 0.252) or NPI-depression (ß = -0.001, p = 0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. CONCLUSIONS: In older adults with T2D, APOE-ε4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression.

Neuropsychiatric profiles in mild cognitive impairment with Lewy bodies.

OBJECTIVES: To compare the neuropsychiatric symptoms (NPS) of patients with mild cognitive impairment with Lewy bodies (MCI-LB) with those with mild cognitive impairment due to Alzheimer's disease (MCI-AD). METHOD: Subjects with probable MCI-LB (n = 53), MCI-AD (n = 60), dementia with Lewy bodies (DLB) (n = 97) and AD (n = 202) were recruited. All were older than 60 years. Neuropsychiatric profiles were evaluated by the Neuropsychiatric Inventory (NPI). The Lewy Body Neuropsychiatric Supportive Symptom Count (LBNSSC) was used to assess give supportive clinical features of DLB (systematized delusions, hallucinations in non-visual modalities, apathy, anxiety, and depression). RESULTS: Compared with MCI-AD, those with MCI-LB had higher total NPI scores on prevalence and severity, as were prevalence and severity in visual hallucinations and rapid eye movement sleep behavior disorder (RBD). The MCI-LB group had a higher LBNSSC than did the MCI-AD group. Compared with 20% of those with MCI-AD, 41.5% of those with MCI-LB had two or more supportive NPS, (likelihood ratio = 2.08, p = 0.013). MCI-LB subjects showed a high prevalence in apathy, depression, and appetite/eating disorders items. CONCLUSION: The NPI is a useful tool to detect NPS in those with MCI-LB. The MCI-LB group had a higher prevalence of core features (visual hallucinations and RBD) and a higher LBNSSC than the MCI-AD group. These features could help to differentiate MCI-LB and MCI-AD.

Mortality in patients with behavioural and psychological symptoms of dementia: a registry-based study.

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are common in patients with dementia. In the elderly population, comorbidities frequently coexist with dementia and mortality in dementia is high. The aim of this study was to investigate the impact of BPSD on mortality in severe dementia. METHODS: This study of 11,448 individuals was based on linked information from the Swedish BPSD registry, the National Patient Register and the Cause of Death register. BPSD was assessed with the Neuropsychiatric Inventory (NPI). Cox proportional hazards regressions were performed for survival analysis. To study different degrees of BPSD, data was categorized into groups: no (NPI, 0 points), mild (NPI, 1-3 points on ≥1 item), moderate (NPI, 4-8 points on ≥1 item) and severe (NPI, 9-12 points on ≥1 item) BPSD based on the highest score on any of the BPSD assessed (NPI items). RESULTS: The presence of moderate or severe BPSD was associated with a stepwise increased risk of mortality (hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.08-1.60 and HR 1.74; 95% CI 1.44-2.12, respectively) compared with individuals with no BPSD. In addition, there was an association between total NPI score and mortality (HR 1.01; 95% CI 1.007-1.010). The results remained significant after multivariable adjustment for age, sex, dementia diagnosis, medication, previous myocardial infarction, hip fracture and stroke. CONCLUSIONS: The results show a stepwise increase in mortality risk with increased BPSD, highlighting the importance of adequate management of BPSD to reduce mortality in dementia.