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PubMedDate not supplied

ADCS Prevention Instrument Project: behavioral measures in primary prevention trials.

BACKGROUND: There is an urgent need for the development of inexpensive, reliable, and valid instruments that can be used in large-scale primary prevention trials of compounds aimed at ameliorating progression from normal aging to mild cognitive impairment or Alzheimer disease. The Alzheimer's Disease Cooperative Study launched a Prevention Instrument Project to develop such methodologies. Behavioral changes are common in diseases causing dementia and may occur prior to a point when cognitive changes are sufficiently severe to allow diagnosis of a dementia syndrome. Experimental behavioral measures were included in the protocol to examine this hypothesis. METHODS: Six hundred forty-four individuals with CDR 0 or 0.5 were randomly assigned to receive a brief in-clinic behavioral assessment or telephonic administration of the same assessment. The questions were asked to the individual and their research partner. The Prevention Instrument Project included behavioral measures of depression, anxiety, irritability, and apathy. RESULTS: All measures demonstrated acceptable test-retest reliability at 3-month intervals except for the single-item depression screen by the subjects' research partner. Behavioral changes are significantly more common among patients with Clinical Dementia Rating (CDR) scores of 0.5 compared with CDR scores of 0. Behavioral alterations including irritability, anxiety, and apathy are more common among ethnic minorities than among the White population. Depression, irritability, anxiety, and apathy are significantly correlated with each other. CONCLUSIONS: Behavioral changes are common among those with mild degrees of cognitive compromise (CDR 0.5). Telephonic assessment of behavioral changes is feasible. The predictive value of these alterations for progression to Alzheimer disease or other dementias will be assessed longitudinally.

Activities of Daily Living↗

PubMed1992

Influences of prolonged bed rest and cognitive impairment on nursing home residents.

Seventy nursing home residents with and 87 without cerebrovascular diseases (CVD) were examined by the modified Stockton Geriatric Rating Scale (modified SGRS) which measures four aspects of impairments; physical disability, socially irritating behavior, communication failure and apathy. They were divided into 3 subgroups according to walking ability; prolonged bed rest, walking with aids and walking by themselves in both groups. Physical disability of mental decline was significantly aggravated more than that of normal intelligence in all the subgroups. Although communication failure and apathy of mental decline had deteriorated more than those of normal intelligence in prolonged bed rest in residents without CVD, apathy of the former had deteriorated more than that of the latter in walking by themselves in residents with CVD.

Aged↗

PubMed2005

Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients.

In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimer's disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms.

Affective Symptoms↗

PubMed2005

Neuropsychiatric symptoms in patients with multiple sclerosis.

OBJECTIVE: To explore the range of psychiatric symptoms in patients with multiple sclerosis (MS) and their association with neurological disability. METHOD: Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties, western Norway, were included. Psychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI). Patients with systemic lupus erythematosus (SLE) served as controls. RESULTS: Eighty-six of 93 eligible MS patients were included, and 80% showed at least one psychiatric symptom. The most frequent symptoms were depression (59%), sleep disturbance (48%), irritability/emotional lability (42%), and apathy (31%). Depression was associated with higher disability score. MS patients showed significantly higher NPI irritability score (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01) than SLE patients. CONCLUSION: Neuropsychiatric symptoms occur frequently in patients with MS. Irritability and apathy are independent of disability and chronic disease and represent unique disease manifestations.

Adult↗

PubMed2006

Impact of behavioural problems on spousal caregivers: a comparison between Alzheimer's disease and frontotemporal dementia.

BACKGROUND: Behavioural changes are a key factor in distinguishing frontotemporal dementia (FTD) from Alzheimer's disease (AD), however, little is known about the impact of these changes on caregivers. The aim of this study was to compare caregivers' distress related to behavioural symptoms of AD and FTD. METHODS: 47 spouse caregivers of consecutively referred patients with AD and 27 spouse caregivers of patients with FTD participated in this study. Behavioural disturbances in the patient and caregivers' emotional reactions were measured with the Neuropsychiatric Inventory. RESULTS: Patients with FTD had significantly higher levels of agitation, apathy, disinhibition and aberrant motor behaviour than did patients with AD. High distress scores were found for disinhibition, depression and apathy in caregivers of FTD patients whereas caregivers of AD patients reported patient apathy, depression and anxiety as being severely distressing. Higher mean distress scores were found for disinhibition in the FTD group. Furthermore, caregivers of FTD patients reported higher levels of general burden, and felt less competent than AD caregivers. CONCLUSIONS: Caregivers of FTD patients were overall more distressed by the behaviour of their partners than were the caregivers of AD patients. Findings from this study underscore the importance of differentiating between diagnostic groups and specific behavioural domains when focusing on caregiver reactions to problem behaviour.

Aged↗

PubMedDate not supplied

The paramedian diencephalic syndrome: a dynamic phenomenon.

The paramedian diencephalic syndrome is characterized by a clinical triad: hypersomnolent apathy, amnesic syndrome, and impaired vertical gaze. We studied 4 cases with computed tomography evidence of bilateral diencephalic infarctions. Each case began abruptly with hypersomnolent apathy followed by fluctuations from appropriate affect, full orientation, and alertness to labile mood, confabulation, and apathy. Speech varied from hypophonia to normal; handwriting varied from legible script to gross scrawl. Psychological testing revealed poor learning and recall, with low performance scores. In 3 patients the predominant abnormality was in downward gaze.

Affective Symptoms↗

PubMed2005

Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials.

OBJECTIVE: The authors explored the effect of galantamine on behavioral symptoms in Alzheimer disease (AD). METHODS: Data were pooled from 2,033 subjects with mild-to-moderate AD who had participated in one of three randomized, double-blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects included in this post hoc analysis had received treatment with either placebo (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg. Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations; 2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition, elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant motor behavior. RESULTS: At endpoint, mean changes from baseline in NPI scores were significantly different between galantamine-treated subjects and placebo-treated subjects, favoring galantamine for several measures: total NPI, individual domains of agitation/aggression, anxiety, disinhibition, and aberrant motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was small. CONCLUSIONS: In this pooled sample of more than 2,000 subjects with mild-to-moderate AD, those who received galantamine therapy experienced modestly better, but statistically significant, outcomes in their behavioral symptoms than placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and aberrant motor behaviors may represent a specific group of cholinergic-responsive behavioral symptoms.

Aged↗

PubMed2005

Specificity of symptoms of depression in Alzheimer disease: a longitudinal analysis.

OBJECTIVE: Authors examined the temporal stability of symptoms of major and minor depression and apathy in dementia. METHODS: A consecutive sample of 65 patients with Alzheimer disease (AD) and depression at baseline evaluation received a follow-up psychiatric assessment that included the Structured Clinical Interview for DSM-IV and the Hamilton Rating Scale for Depression an average of 17 months later. RESULTS: Half of the sample had no depression at follow-up, and showed a significant improvement in sadness, guilt, suicidal ideation, disruption in sleep, loss of interest, loss of energy, thoughts of death, social withdrawal, psychomotor changes, changes in appetite/weight, and symptoms of anxiety. No significant changes were found on scores of irritability or apathy. CONCLUSIONS: The study demonstrates the specificity of depressive symptoms in AD and suggests that apathy and depression are different behavioral domains.

Aged↗

PubMed2001

Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease.

Positron emission tomography was used to evaluate 3 Alzheimer's disease (AD) patients: 1 with major depression, 1 with emotional lability, and 1 with apathy. Compared with 5 non-mood-disordered AD patients, the patient with depression had diminished relative regional cerebral blood flow (rel-CBF) in the anterior cingulate and superior temporal cortices, bilaterally. This patient also showed diminished rel-CBF in the left dorsolateral prefrontal and right medial temporal and parietal cortices. The patient with emotional lability had diminished rel-CBF in the anterior cingulate and dorsolateral prefrontal cortices, bilaterally, and left basal ganglia. The patient with apathy had diminished rel-CBF in the basal ganglia and dorsolateral prefrontal cortex, bilaterally. Results are consistent with the hypothesis of a common frontal-temporal-subcortical substrate (e.g., involving aminergic nuclei) in the etiology of depression in AD. Frontal-subcortical dysfunction may also be associated with emotional lability and apathy in AD, although these may be related to a greater involvement of frontal-basal ganglia circuits.

Affect↗

PubMed2006

A comparison of depressive mood of older adults in a community, nursing homes, and a geriatric hospital: factor analysis of Geriatric Depression Scale.

The Geriatric Depression Scale (GDS)-15 was used in 607 adults aged 65+ years living in a community, nursing homes, and a general hospital to explore characteristics of depressive mood in different care settings. Factor analysis of GDS-15 extracted 4 factors labeled unhappiness, apathy and anxiety, loss of hope and morale, and energy loss. The scale scores labeled unhappiness, apathy and anxiety, and loss of hope and morale were negatively correlated with the Barthel Index and the Mini-Mental State Examination scores. The results classified the depressive patterns into 2 types, one fitting the nursing home residents and the other fitting the hospital patients. The dominant factors of the nursing-home type were unhappiness and loss of hope and morale, and the hospital type was highly related with apathy and anxiety. The results indicate an extended utility of the GDS-15 for a deeper understanding of depressive mood in various care settings.

Activities of Daily Living↗

PubMed2005

Effects of home massage rehabilitation therapy for the bed-ridden elderly: a pilot trial with a three-month follow-up.

OBJECTIVES: To assess the effects of home massage rehabilitation therapy on the bed-ridden elderly. DESIGN: Alternatively allocated trial. SETTING: Subjects' homes, three home nursing stations, 13 visit care stations and one day service centre in Aichi prefecture, Japan. SUBJECTS: Bed-ridden patients who were 65 years and above, no dementia, stable general condition, and receiving no rehabilitation therapy. INTERVENTION: Thirty-minute sessions of home massage rehabilitation therapy by a massage practitioner 2 or 3 days a week for three consecutive months or usual care. MAIN MEASUREMENTS: Barthel Index (BI), Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score. RESULTS: Fifty-three subjects were recruited, 26 in the home massage rehabilitation group (HMG) and 27 in the routine care group without massage (RCG). The protocol was completed for 40 subjects, 22 in the HMG and 18 in the RCG. There were no significant differences between the baseline characteristics of both groups; age, presence of spouse, diseases associated with disabilities and use of day care rehabilitation (p = 0.76, 0.36, 0.94 and 0.71, respectively). The total BI score of the HMG (15.27+/-4.51) at baseline was nonsignificantly lower (p= 0.03) than those of the RCG (11.44+/-5.90). Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score of both groups at baseline were matched (p = 0.12, 0.32 and 0.89, respectively). There were no statistical differences between the intergroup changes over time in BI, Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score (p = 0.35, 0.08, 0.70 and 0.55, respectively). CONCLUSION: Home massage rehabilitation therapy did not show a positive effect on the bed-ridden elderly, either mentally or physically. We would require large-size trials to determine whether it is effective.

Activities of Daily Living↗

PubMed1996

The spectrum of behavioral changes in Alzheimer's disease.

We investigated the range of behavioral abnormalities in patients with Alzheimer's disease (AD) compared with normal age-matched control subjects. The range of behavioral disturbances manifested and the relationship between specific abnormalities with the level of cognitive impairment have not been established. Fifty consecutive outpatients with mild (n = 17), moderate (n = 20), and severe (n = 13) AD and 40 age-matched normal controls were evaluated for behavioral abnormalities occurring in the month preceding the interview. The caregivers of the patients and the spouses of the control subjects were interviewed with the Neuropsychiatric Inventory (NPI). The frequency and severity of the following 10 behaviors were assessed: delusions, hallucinations, agitation, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor behavior. Correlations among these 10 behaviors and their relationship with cognitive impairment were also investigated. Eighty-eight percent of AD patients had measurable behavioral changes. All 10 behaviors were significantly increased in the AD patients compared with normal subjects. The most common behavior was apathy, which was exhibited by 72% of patients, followed by agitation (60%), anxiety (48%), irritability (42%), dysphoria and aberrant motor behavior (both 38%), disinhibition (36%), delusions (22%), and hallucinations (10%). Agitation, dysphoria, apathy, and aberrant motor behavior were significantly correlated wit cognitive impairment.

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PubMed1996

Neuropsychiatric aspects of progressive supranuclear palsy.

Administering the Neuropsychiatric Inventory (NPI), we examined the behavioral symptoms of 22 patients with progressive supranuclear palsy (PSP), 50 patients with Alzheimer's disease, and 40 controls. PSP patients exhibited apathy (91%), disinhibition (36%), dysphoria (18%) and anxiety (18%), but rarely (< 9%) irritability, abnormal motor behaviors, or agitation. Apathy in PSP was significantly associated with executive dysfunction. The presence of high apathy and low agitation and anxiety scale scores correctly identified the PSP patients 85% of the time. Evaluating the behavioral abnormalities of patients with neurodegenerative disorders will aid diagnosis and facilitate management.

Aged↗

PubMed1999

Mechanisms underlying diminished novelty-seeking behavior in patients with probable Alzheimer's disease.

OBJECTIVE: To better understand apathy and disengagement in patients with Alzheimer's disease (AD), the authors investigated possible behavioral mechanisms underlying diminished novelty-seeking activity in patients with probable AD. BACKGROUND: Apathy and disengagement have been shown to be the most common behavioral changes associated with AD. METHOD: Patients and age-matched normal controls had their eye movements recorded while pairs of line drawings pitting an incongruous figure against a congruous figure were shown on a screen for 12 seconds. Characteristics of a subset of AD patients who were indifferent to novel visual stimuli as measured by exploratory eye movements were compared to those of a subset of AD patients who were attracted to novel stimuli to a degree similar to that of normal controls. RESULTS: The indifferent patients were judged by informants, who completed a personality questionnaire, to exhibit a greater degree of apathy. The two AD groups did not differ in overall dementia severity or performance on a Saccade-to-Target Task that required shifts of attention and gaze. In a separate task, the indifferent patients were able to accurately identify the more novel stimuli in 97.5% of trials. Normal control subjects exhibited a strong bias toward processing novel stimuli, directing a higher proportion of their first fixations and dwell time to the incongruous stimuli whether the analysis was run for 3, 6, or 12 seconds of viewing. Indifferent patients did not direct their initial fixation toward novel stimuli and distributed their looking time evenly between incongruous and congruous stimuli throughout all measured intervals. CONCLUSIONS: The results suggest that the indifference to novelty observed in some patients with probable AD cannot simply be attributed to global cognitive decline, more elementary attentional deficits, more rapid habituation of response to novel stimuli, or an inability to discriminate upon demand between stimuli of varying degrees of novelty. It is more likely that their behavior reflects a disruption, by AD pathology, of neural systems that modulate behavioral engagement and maintain attentional bias toward novel events in the environment.

Aged↗

PubMed2000

The acute behavioral syndrome of anterior thalamic infarction: a prospective study of 12 cases.

Using systematic investigations, including neurological and neuropsychological examinations and computed tomography and magnetic resonance imaging analyzed on anatomical maps, we prospectively studied 12 patients (age range, 63+/-19 years) with an isolated anterior thalamic infarct. They had acute, severe, perseverative behavior, which was apparent in thinking, speech, and all memory and executive tasks, combined with increased sensitivity to interference. They also showed superimposition of mental activities normally processed sequentially (e.g., giving biographical information while working on a calculation test), which we called palipsychism (from the Greek palin [again] and the Greek psyche [soul]). In addition, all 12 patients (8 with a left-sided infarct, 4 with a right-sided infarct) had word-finding difficulties, 7 of 12 with impaired naming, 8 of 12 with dysarthria, and 5 of 12 with hypophonia. Comprehension, repetition, written abilities, and reasoning were consistently preserved, but apathy was usual. All patients had anterograde memory impairment, with a delayed recall deficit, primarily verbal in left-sided infarcts and visuospatial in right-sided infarcts. Dysexecutive features such as difficulty in programming motor sequences were always present. Visual neglect or topographic disorientation was found in 3 patients. Magnetic resonance imaging emphasized involvement of the anterior group of thalamic nuclei, the mamillothalamic tract, and the anterior part of the internal medullary lamina, with structural sparing of the dorsomedial and ventrolateral nuclei. Sequential follow-up examinations showed spectacular improvement within a few months, with the only significant persisting abnormalities being memory dysfunction and apathy. The acute behavioral syndrome of anterior thalamic infarction is dominated by palipsychism, which corresponds to an overlap of sequential cognitive processes in two or more domains. Its association with severe perseverative behavior with increased sensitivity to interference, anterograde memory retrieval deficit, intrusions, naming difficulties with dysarthria and hypophonia, and apathy is suggestive of this type of infarct.

Anterior Thalamic Nuclei↗

PubMed2002

The prevalence and correlates of neuropsychiatric symptoms in a population with Parkinson's disease in Mexico.

OBJECTIVE: To study the incidence of behavioral abnormalities in patients with Parkinson's disease (PD) and extend them to a Mexican population. BACKGROUND: Reports from the US and Europe suggest depression, anxiety, and apathy occur with increased frequency in PD, but data on the occurrence of neuropsychiatric symptoms in patients with PD in Latin America are lacking. METHODS: The investigators performed a cross-sectional survey of psychiatric symptoms and cognitive status in 40 patients with PD and 83 controls in Mexico City. RESULTS: Results were compared between groups and correlations sought between symptoms and disease variables. Patients with PD had a higher rate of dysphoria, anxiety, and apathy (p < 0.001). Within the patients with PD, there was a positive correlation between disease severity (rho = 0.496), age (rho = 0.340), and degree of self-rated depression. CONCLUSIONS: This study confirmed the observation previously described in other PD populations of increased rates of dysphoria, anxiety, and apathy in Mexican patients with PD. We found no relation between disease duration, severity, cognitive impairment, and neuropsychiatric symptoms as measured on the Neuropsychiatric Inventory, possibly a result of the relative lack of advanced cases in our population.

Aged↗

PubMed2004

[Depression and dementia].

Data from the literature devoted to the relationships between dementia and depression are controversial on account of numerous methodological biases (community studies or from neurological or psychiatric departments), categorical versus dimensional approaches and variability of assessment tools for depression, aim of the study (depression versus dementia or versus Alzheimer's disease, AD). The difficulty to discriminate depression from AD is largely overestimated due to the confusion between depression, depressive symptomatology and apathy. The distinction is greatly facilitated by taking into account the qualitative differences of the memory deficits and cerebral imagery. Distinction of depression from frontotemporal or subcortical dementias could be much more difficult. Relationships between depression and AD are controversial. Most reports of depression as a risk factor for AD in the subsequent years, actually describe depressed symptomatology linked to apathy in preclinical AD. However, some studies found a relationship between AD and depression occurring more than 10 years before the onset of AD symptomatology, suggesting some common risk factors. The so-called symptoms of depression in AD are more related to apathy and affective disturbances than to dysphoria. The frequency of major depressive episode (MDE), greatly varies according to studies, but the frequency of suicide is low. Depression in dementia is related to neurobiological factors as well as to psychological mechanisms. Therefore, its treatment should associate antidepressant drugs and psychological support directed to the patient and family.

Aged↗

PubMed2005

Disorders of motivation, sexual conduct, and sleep in Parkinson's disease.

Apathy and fatigue, sexual disturbances, mania, sleep disturbances, personality changes, pathologic gambling, and addiction to antiparkinson agents occur in patients with PD and may pose considerable stress on the patients themselves and their caregivers. With the exception of apathy and fatigue, little is known regarding the prevalence of these symptoms in patients with PD. The pathophysiologic mechanisms are unknown, although disturbances of the mesolimbic and mesocortical dopaminergic pathways are probably involved. Antiparkinsonian drugs or surgery seem to be the main etiologic factors for sexual disturbance, hypomania, addiction, and pathologic gambling, whereas hypodopaminergic states may contribute to symptoms such as apathy, fatigue, RBD, and possibly personality changes. Although some placebo-controlled trials have been published recently, no established treatments are currently available for these symptoms (85) (see Table 5-2), and thus future clinical trials are needed.

Animals↗