Grouping and trajectories of neuropsychiatric symptoms in patients with Alzheimer's disease. Part II: two-year patient trajectories

Behavioral and psychological symptoms of dementia (BPSD) are characterized by fluctuations in their frequency and severity as well as by differences in the concurrent presentation of different symptoms. The goal of the current study was to identify groups of patients with Alzheimer's disease (AD) that had similar trajectories in the expression of BPSD. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild or moderate severity. The Neuropsychiatric Inventory (NPI) was administered every 6 months to the patient's caregiver. To classify patients according to changes in the frequency and severity of BPSD, growth mixture models were fitted to the applied to the grouping of NPI subscales in the following three categories: psychotic syndrome (hallucinations and delusions), affective syndrome (depression, anxiety, irritability, and agitation), and behavioral syndrome (disinhibition, euphoria, apathy, and aberrant motor behavior). The sample population consisted of 491 patients (70.9% women) that had an average age of 75.2 years (SD=6.6). Different trajectory patterns were identified based on differences in changes over the time in the frequency (stable, increasing, decreasing, or fluctuating in course) and severity (low, moderate, or elevated severity) for psychotic syndrome, emotional syndrome, and behavior syndrome. Patients with AD display a high degree of variability in the evolutionary course of BPSD. It is possible to identify groups of patients with similar evolutionary trajectories in terms of changes in the frequency and severity of BPSD.     

Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease

Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome and/or a “risk factor” of neurodegenerative diseases. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer's disease (AD) and Parkinson's disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.     

Depressive symptoms in patients with Alzheimer's disease

OBJECTIVES: A comparison was made between the depressive symptom profiles of thirty patients with Alzheimer's disease (AD) who did not have co-existing depression and thirty patients with major depression who did not have co-existing dementia. The main objective was to identify symptoms common to both disorders and those which may be able to differentiate AD from major depression. METHOD: A sample of patients suffering from either AD (n = 30) or major depression (n = 30) were recruited from a specialist old age psychiatry service. Depressive symptoms were profiled using the Hamilton Depression Rating Scale (HDRS), the Cornell Scale for Depression in Dementia (CSDD) and the Geriatric Depression Scale (GDS). RESULTS: Depressive symptoms were present in AD in the absence of coexistent major depression. Certain depressive symptoms from all the three scales such as sadness, diurnal variation in mood and early or late insomnia were able to differentiate the two disorders with almost 90% accuracy while symptoms such as irritability, retardation and weight loss were common to both and were unable to differentiate the two. CONCLUSION: Depressive symptoms occur in AD when co-existing depression is ruled out. Their recognition has implications for the diagnosis of major depression in these patients.     

Effect of neuropsychiatric symptoms of Alzheimer's disease on Chinese and American caregivers.

BACKGROUND: In Chinese culture, extended family support, acceptance of age-related cognitive changes and filial tradition of caring for elders may decrease caregiver burden and distress in the context of dementia. OBJECTIVE: To study cross-regional and cross-cultural differences in symptom-related caregiver distress due to the behavioral problems of Chinese and American patients with Alzheimer's disease. METHOD: Caregivers of patients with Alzheimer's disease at Taipei Veterans General Hospital, Taiwan (n = 89), Chinese University of Hong Kong (n = 31) and the UCLA Alzheimer's Disease Research Center, Los Angeles, California (n = 169) reported the neuropsychiatric symptoms of patients and their corresponding distress on the Neuropsychiatric Inventory. RESULT: Presence or absence of distress due to the neuropsychiatric symptoms of the patients with Alzheimer's disease was assessed. The three centers differed significantly in the proportions of caregivers with distress caused by depression (p < 0.05) and apathy (p < 0.001). UCLA had higher proportions of caregivers with depression-related distress than Taipei. UCLA caregivers were also more stressed by apathy than caregivers in Taipei and Hong Kong. Logistic regression further supported the findings that depression-related and apathy-related caregiver distress differed between Chinese and American caregivers (p < 0.05). CONCLUSIONS: The results were surprising, in that American and Chinese (Taipei and Hong Kong) caregivers exhibited similar distress or lack of distress in response to delusions, hallucinations, agitation, anxiety, euphoria, disinhibition, irritability, aberrant motor behavior, sleep and appetite symptoms of Alzheimer's disease patients. Chinese caregivers were less affected by depression and apathy in patients with Alzheimer's disease than Caucasian caregivers.     

Neurobehavioral and neuropsychiatric symptoms in Alzheimer's disease: characteristics and treatment

Neuropsychiatric symptoms are common in Alzheimer's disease. Personality changes, mood disturbance, and psychosis are frequently seen and may coexist in the same patient. Neuropsychiatric symptoms may signal the onset of disease and often fluctuate and recur. These symptoms are associated with a more rapid cognitive and functional decline that can lead to institutionalization. Cholinergic therapy, disease-modifying therapy, and psychotropic medications can improve these symptoms.     

Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer's disease, part I: symptom clusters

Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in Alzheimer's disease (AD) and affect more than 80% of patients over the course of AD. The goal of this study was to establish a model for grouping the symptoms of BPSD into clinical syndromes. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild to moderate severity. The Neuropsychiatric Inventory (NPI) was administered to the patients' caregivers every 6 months. BPSD were grouped using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of the NPI scores of each assessment. The sample population consisted of 491 patients (70.9% women) with an average age of 75.2 years (SD=6.6). The five EFA suggested that there was a stable three-factor structure. According to the results of the EFA, three models of symptom grouping were adjusted using CFA methodology. The CFA model that satisfactorily grouped the NPI scores into three factors included a psychotic syndrome (hallucinations, delusions), an affective syndrome (depression, anxiety, irritability, agitation) and a behavior syndrome (euphoria, disinhibition, apathy, aberrant motor behavior). Based on our findings, we propose a model for grouping the BDSD in which there are core nuclear syndromes (psychotic and affective) as well as an unspecified behavior syndrome comprising satellite symptoms that may be related to the presence of the nuclear syndromes.     

5-HT2A T102C receptor polymorphism and neuropsychiatric symptoms in Alzheimer's disease

OBJECTIVE: To investigate the association between 5-HT(2A) receptor polymorphism and neuropsychiatric (NP) symptoms in Chinese elderly with Alzheimer's disease (AD). METHODS: This case-control study evaluated Chinese subjects with AD first presented to an university affiliated psychogeriatric clinic. Eighty-seven subjects with NINCDS-ADRDA diagnosis for probable and possible AD were recruited consecutively from the psychogeriatric clinics of the Prince of Wales Hospital in Hong Kong. 5-HT(2A) receptor polymorphisms were examined by polymerase chain reaction (PCR), enzyme digestion and gel electrophoresis. NP symptoms were assessed by the Chinese version of the Neuropsychiatric Inventory (NPI). RESULTS: The genotype frequencies were significantly different in subjects with regards to the presentation of delusions, aggression, aberrant motor behavior and apathy (Pearson Chi Squares, p < 0.05). If only homozygote states were included, there were significantly fewer subjects of CC genotype with delusion (Pearson chi square, p < 0.05). CONCLUSIONS: Specific NP symptoms in AD were significantly associated with 5-HT(2A) receptor polymorphisms. Possible ethnic differences in the behavioral expression of 5-HT(2A) receptor polymorphisms are worthy of further exploration.     

Facial expression in Alzheimer's disease: impact of cognitive deficits and neuropsychiatric symptoms

In Alzheimer's disease (AD), nonverbal aspects of communication become increasingly important in caregiver-patient interactions when the ability to communicate verbally is fading with progression of the disease. We therefore investigated the impact of cognitive deficits and neuropsychiatric symptoms, particularly apathy, on facial expression in AD. While overall neuropsychiatric symptoms were not associated with facial expression, apathy exhibited substantial correlations, even after controlling for cognitive deficits. Moreover, apathy appeared to moderate the influence of cognitive deficits: without considering apathy, cognitive deficits were associated with less specific facial expressions. After controlling for apathy, cognitive decline was related to increased facial expressiveness. In conclusion, apathetic symptoms appear to be specifically associated with facial expression in AD and thus could contribute to a disregard for patients' needs in everyday life.     

History of major depression is associated with neuropsychiatric symptoms but not systemic inflammation in a cross-sectional study in obese patients

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship.A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m²) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants.Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only.Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity.     

Innovations: geriatric psychiatry: diagnosis and treatment of neuropsychiatric symptoms in Alzheimer's disease

The authors review research on the treatment of behavioral disturbances and psychiatric symptoms of patients with dementia, including pharmacological treatment with antipsychotics, antidepressants, cholinesterase inhibitors, and other psychotropic drugs. They conclude that although these medications have some beneficial effects, no intervention is currently able to eradicate behavioral disturbances and psychiatric symptoms of demented patients. Research suggests that multiple interventions for an individual patient are likely to replace the use of a single treatment. Such interventions include caregiver training and support, antipsychotics, antidepressants, and cholinesterase inhibitors, along with other drugs developed for the treatment of Alzheimer's disease.     

Longitudinal cognitive changes in patients with early Parkinson's disease and neuropsychiatric symptoms

Aims

In this study, we aimed to investigate the effect of neuropsychiatric symptoms (NPS) on the rate of cognitive decline for both global cognition and specific cognitive domains in a cohort of patients from the Parkinson's Progression Markers Initiative (PPMI).

Method

Prospectively longitudinal data were obtained from the PPMI cohort. NPS, including depression, anxiety, apathy, psychosis, impulse control disorders (ICDs), and cognition ability, were evaluated by a series of questionnaires. Linear mixed-effects models were used to investigate the relationship between NPS and the rate of cognitive decline. Generalized estimating equations (GEEs) were used to investigate the relationship between NPS and the occurrence of mild cognitive impairment (MCI).

Results

In total, 423 patients with Parkinson's disease (PD) were recruited at baseline and 395, 378, 366, 346, and 315 participants were followed up at 1, 2, 3, 4, and 5 years, respectively. Depression, anxiety, apathy, and psychosis were associated with global cognitive decline. Except for those with ICDs, patients with psychosis, depression, anxiety, and apathy were more likely to meet the criteria for MCI. Patients with depression and anxiety showed a progressive decline in four major cognitive domains. Apathy and ICDs were separately associated with a progressive decline in processing speed-attention and memory, respectively.

Conclusions

Neuropsychiatric symptoms, including psychosis, depression, anxiety, and apathy, could be used to predict future cognitive decline in patients with PD.     

Antipsychotic drug use and associations with neuropsychiatric symptoms in persons with impaired cognition: a cross-sectional study

Background: Neuropsychiatric symptoms (NPS) in cognitive disorders impair quality of life, increase caregiver stress, and may lead to earlier institutionalization and death. The objective of this study was to investigate the use of antipsychotics among persons with cognitive impairment in home care and residential care, and its associations with NPS and personal characteristics.

Methods: Data were collected in the South Savo Hospital District area with 105 000 inhabitants, where 66 of 68 institutions providing long-term residential care and 20 of 21 municipal home care producers joined the study. Nurses recorded the current use of drugs, the activities of daily living (ADL), prevalence of diagnosed dementia, and assessed the cognitive status and the prevalence of recent NPS based on the item list of the Neuropsychiatric Inventory (NPI).

Results: The study population was 1909 persons with cognitive impairment, and 1188 of them lived in residential care. Antipsychotics were used by 563 (29.5%) persons in the whole study population. In residential care 448 (37.7%) used antipsychotics and the corresponding figure in home care was 115 (15.9%). In the multivariate analysis, the antipsychotic use was associated with living in residential care, benzodiazepine use, and with NPS symptoms agitation/aggression (OR =1.70, 95% CI =1.16–2.48), disinhibition (OR =2.33, 95% CI =1.31–4.15), hallucinations (OR =2.77, 95% CI =1.69–4.55), and delusions (OR =1.71, 95% CI =1.01–2.91).

Conclusions: Antipsychotic use was common among persons with cognitive impairment. The results suggest that antipsychotics are commonly used to treat hyperactivity and psychotic symptoms, especially in residential care.     

The specificity of depressive symptoms in patients with Alzheimer's disease

OBJECTIVE: This study assessed the specificity of depressive symptoms in patients with Alzheimer's disease and examined the discrepancies between patient and caregiver symptom reports. METHOD: The study group was composed of a series of 233 patients with Alzheimer's disease, 47 patients with depression but without dementia, and 20 healthy comparison subjects; the latter two groups were comparable in age with the patients with Alzheimer's disease. The patients and comparison subjects received a comprehensive psychiatric evaluation, which included administration of the Hamilton Depression Rating Scale and the Structured Clinical Interview for DSM-IV. RESULTS: Patients with Alzheimer's disease with a score of 2 or higher on the "depressed mood" item of the Hamilton depression scale, as scored by their respective caregivers, comprised a group with depressed mood (N=92), whereas patients who scored 0 on this item comprised a group without depressed mood (N=62). A statistical comparison of the scores on the remaining Hamilton depression scale items (2-16) between the Alzheimer's disease patients with and without depressed mood revealed significant differences on all items, except "loss of appetite." However, there were no significant differences on any single Hamilton depression scale item between the Alzheimer's disease patients without depressed mood and the age-comparable healthy comparison subjects. CONCLUSIONS: Depressive symptoms are not widespread among patients with Alzheimer's disease but are significantly related to an underlying depressed mood. Patients with Alzheimer's disease may not be fully aware of the extent of their depressive symptoms.