A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

Attenuation of neuropsychiatric symptoms and caregiver burden in Alzheimer's disease by motor intervention: a controlled trial

OBJECTIVE: To analyze the effects of motor intervention on the neuropsychiatric symptoms of Alzheimer's disease and on the caregivers' burden. DESIGN: This is a controlled trial evaluating the effects of a motor intervention program on the neuropsychiatric symptoms. SETTING: The intervention was performed on community patients from two university centers specializing in physical exercise for the elderly. SUBJECTS: Patients with Alzheimer's disease were divided into two groups: sixteen received the motor intervention and sixteen controls (five controls were excluded because of clinical intercurrences). INTERVENTIONS: Aerobic exercises (flexibility, strength, and agility) and functional balance exercises were conducted over six months for 60 minutes three times per week. MAIN MEASURES: Psychopathological features of patients were evaluated with the Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Caregivers were evaluated using the Neuropsychiatric Inventory-Distress and Burden Interview. A two-way analysis of variance (ANOVA) was applied to observe interactions (pre- vs. post-intervention; participants vs. controls). RESULTS: Patients from the intervention presented a significant reduction in neuropsychiatric conditions when compared to controls (Neuropsychiatric Inventory: F: 11.12; p = 0.01; Cornell Depression scale: F: 11.97; p = 0.01). The burden and stress of caregivers responsible for patients who participated in the intervention significantly decreased when compared to caregivers responsible for controls (Neuropsychiatric Inventory-Distress: F: 9.37; p = 0.01; Burden Interview: F: 11.28; p = 0.01). CONCLUSIONS: Aerobic exercise was associated with a reduction in the neuropsychiatric symptoms and contributed to attenuate the caregivers' burden. However, the researchers were not blinded to the patient's intervention status, which constitutes an important limitation of this study.

The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): Reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia

Background: Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages). Methods: Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity. Results: Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains. Conclusion: Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies. Copyright © 2010 International Psychogeriatric Association.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or resting-state analysis, may help to clarify this issue. Using such approaches, alterations in the default-mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting-state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default-mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. © 2013 Wiley Periodicals, Inc.

Neuropsychiatric symptoms in the prodromal stages of dementia

Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.

Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer's disease patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Examining carer stress in dementia: the role of subtype diagnosis and neuropsychiatric symptoms

INTRODUCTION: Caring for people with dementia incurs significant stress for carers. Stress has been related to the duration of caring role, the number of weekly hours provided and severity of cognitive impairment. What remains less clear is the impact of neuropsychiatric symptoms and subtype of dementia on carer stress and this study aimed to examine these. METHODS: Dementia carers were recruited for people with a range of dementia subtypes. Carers were interviewed using the Neuropsychiatric Inventory with the Carer Distress Scale. Cognitive fluctuations were assessed using the Dementia Cognitive Fluctuations Scale. All patients were also examined with The Cambridge Assessment for mental disorders in the elderly. RESULTS: Dementia diagnostic subtype, the presence of cognitive fluctuations and some neuropsychiatric symptoms (psychosis and mood disturbance) did predict carer stress (all at p < 0.01) but age, gender and severity of cognitive impairment did not (all p > 0.33). Carers of people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) experienced more stress than those caring for patients with Alzheimer's disease and vascular dementia. Carer stress was associated with higher levels of psychosis, mood disturbances, daytime sleep and cognitive fluctuations in the person with dementia. CONCLUSIONS: This study identified the significant impact on carers of providing care for people with DLB and PDD dementia subtypes and also highlighted the significant impact of providing care for patients with high levels of psychosis, mood disturbances and cognitive fluctuations.

Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Physical activity attenuates neuropsychiatric disturbances and caregiver burden in patients with dementia

INTRODUCTION: A significant benefit from physical activity has recently been described in some patients who suffer from neurodegenerative diseases. OBJECTIVE: To assess the effects of physical activity on neuropsychiatric disturbances in demented patients and on the mental burden of their caregivers. METHODS: Assisted by a public geriatric psychiatry clinical unit, we studied 59 patients with dementia. Patients were divided into three groups according to their diagnosis and level of physical activity. Data were assessed through a semi-structured interview. Patients were evaluated with the Neuropsychiatric Inventory, the Mini-Sleep Questionnaire and the Baecke Questionnaire. The data were statistically analyzed using the Mann-Whitney U test and linear regression, with the level of significance set at 5%. RESULTS: Patients with Alzheimer's or vascular dementia who engaged in physical activity had fewer neuropsychiatric symptoms than those who did not. When compared to the control group, the caregivers of patients with vascular dementia who engaged in physical activity had a reduced burden. CONCLUSION: The regular practice of physical activity seems to contribute to a reduction in neuropsychiatric symptoms in dementia patients and to attenuate the burden of the caregivers of those patients.