Anxiety Disorders: Cummings JL

Apostolova LG, Cummings JL. · Department of Neurology, David Geffen School of Medicine, UCLA, USA. · Dement Geriatr Cogn Disord. · Pubmed #18087152 No free full text.

Abstract: BACKGROUND: Mild cognitive impairment (MCI) is an etiologically heterogeneous condition that is characterized by cognitive changes without impairment of activities of daily living and insufficient to represent dementia. MCI is an important risk state for dementia. Neuropsychiatric symptoms may be present in MCI. METHODS: We executed a PubMed search for articles on the neuropsychiatric manifestations in MCI and reviewed their findings. RESULTS: Behavioral abnormalities are reported in 35-75% of MCI patients with the most common being depression, apathy, anxiety and irritability. The observed variability in symptom prevalence can be explained by the different sampling methods, MCI diagnostic criteria and behavioral instruments used. There is a compelling body of evidence that MCI patients with behavioral features are more prone to develop Alzheimer's disease (AD) than patients without these features. CONCLUSIONS: Neuropsychiatric symptoms are common features of MCI. The behavioral changes observed in MCI are similar to those of AD and may help identify the subgroup of MCI patients with prodromal AD. Large prospective longitudinal studies would greatly contribute to our understanding of the epidemiology, diagnostic and prognostic value of the neuropsychiatric features in MCI.

Royall DR, Lauterbach EC, Cummings JL, Reeve A, Rummans TA, Kaufer DI, LaFrance WC, Coffey CE. · The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #12426407 links to  free full text

Abstract: This report reviews the state of the literature and opportunities for research related to "executive control function" (ECF). ECF has recently been separated from the specific cognitive domains (memory, language, and praxis) traditionally used to assess patients. ECF impairment has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. No single putative ECF measure can yet serve as a "gold standard." This and other obstacles to assessment of ECF are reviewed. ECF impairment and related frontal system lesions and metabolic disturbances have been detected in many psychiatric and medical disorders and are strongly associated with functional outcomes, disability, and specific problem behaviors. The prevalence and severity of ECF deficits in many disorders remain to be determined, and treatment has been attempted in only a few disorders. Much more research in these areas is necessary.

Rummans TA, Lauterbach EC, Coffey CE, Royall DR, Cummings JL, Salloway S, Duffy J, Kaufer D. · Mayo Clinic, Rochester, MN 55905, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #10333990 links to  free full text

Abstract: Psychiatric disorders frequently compound the disability and complicate the management of neurologic conditions. These disorders result in increased morbidity for the person afflicted, stress for the caregiver, and financial burden. This study reviews the randomized double-blind placebo-controlled pharmacologic treatment trials of psychosis, depression, anxiety, and agitation in neurologic conditions from 1966 to 1998. Ten studies involving psychosis, 13 involving depression, and 20 involving anxiety-agitation meeting the committee's criteria were identified. Relatively few randomized double-blind placebo-controlled pharmacologic treatment trials of psychiatric disorders complicating neurologic disease have been conducted. These trials do not strongly support one specific pharmacologic approach to treatment. Further study of newer psychotropic agents, augmentation strategies, and novel use of other agents may help improve the treatment of psychiatric disorders observed in patients with neurologic disease.

Cummings JL, Nadel A, Masterman D, Cyrus PA. · Reed Neurological Research Center, University of California at Los Angeles, 90095-1769, USA. · J Geriatr Psychiatry Neurol. · Pubmed #11419566 No free full text.

Abstract: Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.

Cummings JL, Jeste DV. · Departments of Neurology and Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles. · Psychopharmacol Bull. · Pubmed #18227780 No free full text.

Abstract: Background: Neuropsychiatric symptoms are common in many neurologic diseases. Psychosis, depression, agitation, anxiety, irritability, and apathy occur in degenerative, traumatic, vascular, and demyelinating brain diseases. Design: Regulatory policies regarding approval of psychotropic agents for treatment of neuropsychiatric symptoms in neurologic disorders are reviewed. Results: Psychotropic agents previously received broad labeling such as treatment for psychosis or depression. Food and Drug Administration (FDA) policy now requires that labeling be limited to the population included in clinical trials providing the basis for the application. When applying for approval for use of psychotropic agents in neurologic disorders, pharmaceutical companies will be required to demonstrate efficacy in the neurologic disease of interest. Definitions of specific neuropsychiatric symptoms in neurologic diseases are required for study design. Approval will depend on demonstrating efficacy in two independent, randomized, controlled trials with symptom-focused and global outcome measures. Labeling for treatment of a nonspecific symptom (eg, agitation) can be approved if efficacy is demonstrated across several neurologic diseases. Conclusion: Patients with neurologic diseases may have dosage ranges, side effects, or response profiles of psychotropic agents that differ from those of patients with idiopathic psychiatric disorders. FDA policy now requires demonstration of efficacy, safety, and tolerability of psychotropic agents within neurologic disorders, allowing clinicians to make more rational choices regarding treatment options.

Tsang SW, Vinters HV, Cummings JL, Wong PT, Chen CP, Lai MK. · Dementia Research Laboratory, Department of Clinical Research, Singapore General Hospital, Singapore. · Neurobiol Aging. · Pubmed #17433503 No free full text.

Abstract: Glutamatergic deficits are established neuropathological features of Alzheimer's disease (AD) and are known to correlate with cognitive impairments. In contrast, the role of glutamatergic alterations in behavioral and psychological symptoms of dementia (BPSD) is unclear. There is considerable preclinical evidence for the importance of glycine recognition sites (GlyRS) of N-methyl-D-aspartate (NMDA) receptors in the regulation of anxiety behaviors. This study aimed to correlate several glutamatergic measures with chronic anxiety in AD. Twenty-one AD patients assessed by the Neuropsychiatric Inventory (NPI) were divided into low anxiety (LA) and high anxiety (HA) subgroups. GlyRS and NMDA channel were measured by brain homogenate binding with [(3)H]MDL105,519 and [(3)H]MK-801, respectively. Densities of NMDA receptor NR2A, NR2B and alternate spliced NR1 subunits were quantified by immunoblotting. We found that the binding affinity to GlyRS was significantly higher in HA compared to LA, and this higher GlyRS affinity correlated with selective reduction of NR2A density as well as with elevated anxiety scores. Our observations suggest a novel mechanism whereby subunit specific changes in the NMDA receptor complex may be linked to chronic anxiety in AD via effects on GlyRS function. We propose that NR2A and GlyRS should be further assessed as novel targets of behavioral pharmacotherapy in AD.

Cummings JL, Raman R, Ernstrom K, Salmon D, Ferris SH, Anonymous00338. · Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1769, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135808 No free full text.

Abstract: 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.

Ortiz F, Fitten LJ, Cummings JL, Hwang S, Fonseca M. · The Neuropsychiatry Research Memory Clinic, Olive View-UCLA Medical Center, Sylmar, CA 91342, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #16948291 No free full text.

Abstract: The purpose of this study was to characterize and compare neuropsychiatric symptoms in a sample of 367 community-dwelling subjects: 70 Hispanics and 230 non-Hispanic white patients with Alzheimer's disease, and 22 Hispanics and 45 non-Hispanic white healthy age-matched controls. Neuropsychiatric symptoms were common among all patients with Alzheimer's disease. In the Alzheimer's disease groups, Hispanic subjects presented to the initial assessment with more symptoms than non-Hispanic white subjects did. In comparison to the non-Hispanic white population, the proportion of Hispanics with neuropsychiatric and behavioral symptoms was higher. These findings have implications for differential sociocultural presentations of Alzheimer's disease among ethnic/racial groups.

Aarsland D, Brønnick K, Ehrt U, De Deyn PP, Tekin S, Emre M, Cummings JL. · Centre for Clinical Neuroscience Research, Stavanger University Hospital, Stavanger, Norway. · J Neurol Neurosurg Psychiatry. · Pubmed #16820421 No free full text.

Abstract: OBJECTIVE: To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson's disease (PDD). METHODS: 537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed. RESULTS: 89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score > or = 4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson's disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson's Disease Rating Scale and care giver distress scores. CONCLUSION: Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.

Shin IS, Carter M, Masterman D, Fairbanks L, Cummings JL. · Department of Psychiatry, Chonnam National University Medical School, Kwangju, Republic of Korea. · Am J Geriatr Psychiatry. · Pubmed #15956266 No free full text.

Abstract: OBJECTIVE: Authors examined the impact of neuropsychiatric symptoms in Alzheimer disease (AD) patients' and caregivers' quality of life (QOL) and assessed the relationship of caregiver distress to neuropsychiatric symptoms and caregiver QOL. METHODS: Sixty-two patients with probable or possible AD and their caregivers participated. Neuropsychiatric symptoms of patients were assessed with the Neuropsychiatric Inventory (NPI). QOL of both patients and caregivers was assessed using the QOL-Alzheimer's Disease (QOL-AD) scale. Each patient and caregiver completed patient QOL ratings; caregivers also completed caregiver QOL assessments. RESULTS: Caregiver QOL-AD was negatively correlated with agitation/aggression, anxiety, disinhibition, irritability/lability, and total NPI score. Patient QOL on both patient and caregiver ratings was negatively correlated with depression. Patient-reported QOL-AD ratings at different levels of cognitive functioning were not correlated with caregiver-reported ratings. The lack of relationship between patient and caregiver assessments of patient QOL was evident in both mildly and moderately affected patients. Caregiver QOL was negatively correlated with distress related to agitation/aggression, disinhibition, irritability/lability, and total NPI distress. CONCLUSION: Neuropsychiatric symptoms of AD patients adversely affect both patient and caregiver QOL. These results suggest that identifying and treating neuropsychiatric symptoms in AD may improve both patient and caregiver QOL.

Hwang TJ, Masterman DL, Ortiz F, Fairbanks LA, Cummings JL. · Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA. · Alzheimer Dis Assoc Disord. · Pubmed #15195459 No free full text.

Abstract: Mild cognitive impairment (MCI) has emerged as an identifiable condition and in many cases is a transitional state preceding diagnosable Alzheimer disease (AD). Neurobiological and neuroimaging characteristics of amnestic-type MCI have been investigated, but few comprehensive neuropsychiatric studies have been reported. The aim of this preliminary study was to define the neuropsychiatric features of the amnestic-type MCI and compare them with those of mild AD and normal controls. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in three age and education comparable groups, i.e., 28 MCI, 124 mild AD, and 50 normal subjects. Individual subscores of the 10 NPI symptoms and total NPI scores were compared between the MCI patients and the other 2 groups. The results of this preliminary investigation showed that MCI patients frequently manifested neuropsychiatric symptoms. The most common symptoms in the MCI group were dysphoria (39%), apathy (39%), irritability (29%), and anxiety (25%). There were significant differences in apathy, dysphoria, irritability, anxiety, agitation, and aberrant motor behavior between the MCI and control groups; in contrast, only delusions were significantly less common in MCI compared with mild AD. There was a significant difference between the MCI and control groups on total NPI scores (p = 0.001), but not between the MCI and mild AD groups (p = 0.304). Amnestic MCI is associated with significant neuropsychiatric symptoms, especially mood disturbances and apathy. Psychotic symptoms are significantly more common in the early stage of AD than in MCI. These results are derived from a limited clinical sample and require confirmation in longitudinal community-based investigations.

Ringman JM, Diaz-Olavarrieta C, Rodriguez Y, Fairbanks L, Cummings JL. · Department of Neurology, UC Irvine School of Medicine, Irvine, California, USA. · Neuropsychiatry Neuropsychol Behav Neurol. · Pubmed #12050472 No free full text.

Abstract: 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.

Kulisevsky J, Litvan I, Berthier ML, Pascual-Sedano B, Paulsen JS, Cummings JL. · Movement Disorders Unit, Department of Neurology, Sant Pau Hospital, Autonomous University of Barcelona, Spain. · Mov Disord. · Pubmed #11748741 No free full text.

Abstract: The role of the basal ganglia in conditions with co-occurring movement disorders and neuropsychiatric symptoms is not well known. It has been hypothesized that hyperkinesia -disinhibited behaviors and hypokinesia-inhibited behaviors result from an imbalance between the direct and indirect striatal output pathways, and that differential involvement of these pathways could account for the concurrent abnormalities in movement and behavior observed in these disorders. This study aimed to evaluate whether the pattern and the extent of the neuropsychiatric manifestations of patients with GTS, a hyperkinetic movement disorder of basal ganglia origin, differs from that of patients with other basal ganglia hyperkinetic (e.g., HD) or hypokinetic (e.g., PSP) movement disorders, and to determine whether patients with GTS show a greater frequency of hyperactive behaviors (e.g., agitation, irritability, euphoria, or anxiety) than PSP patients, and are comparable to patients with HD. The Neuropsychiatric Inventory (NPI), a scale with established validity and reliability, was administered to 26 patients with GTS (mean age, 30.2 +/- 2.2 years), and the results were compared with that of 29 patients with HD (mean age, 43.8 +/- 2 years) and 34 with PSP (mean +/- S.D. age, 66.6 +/- 1.2 years). There was no difference between the groups in the total NPI scores. However, there was a double dissociation in behaviors: patients with hyperkinetic disorders (HD and GTS) exhibited significantly more agitation, irritability, anxiety, euphoria, and hyperkinesia, whereas hypokinetic patients (PSP) exhibited more apathy. Patients with GTS showed greater scores than HD patients in all those scores differentiating HD and GTS from PSP patients (e.g., agitation, irritability, anxiety and euphoria), and were differentiated in a logistic regression analysis from both HD and PSP patients in having significantly more anxiety. We found that patients with GTS manifested predominantly hyperactive behaviors similar but more pronounced than those presented by patients with HD, while those with PSP manifested hypoactive behaviors. Based on our findings and the proposed models of basal ganglia dysfunction in these disorders, we suggest that the hyperactive behaviors in GTS are comparable to those observed in HD, being both secondary to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation of these circuits. Abnormalities of other brain structures (e.g., amygdala, brainstem nuclei) may account for the significantly higher anxiety scores differentiating GTS from HD patients.

Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL. · Department of Psychiatry, The University of Iowa, 2880 JPP, 200 Hawkins Drive, Iowa City, IA 52242, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #11511702 links to  free full text

Abstract: OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease and have been considered its presenting manifestation. Research characterising these symptoms in Huntington's disease is variable, however, encumbered by limitations within and across studies. Gaining a better understanding of neuropsychiatric symptoms is essential, as these symptoms have implications for disease management, prognosis, and quality of life for patients and caregivers. METHOD: Fifty two patients with Huntington's disease were administered standardised measures of cognition, psychiatric symptoms, and motor abnormalities. Patient caregivers were administered the neuropsychiatric inventory. RESULTS: Ninety eight per cent of the patients exhibited neuropsychiatric symptoms, the most prevalent being dysphoria, agitation, irritability, apathy, and anxiety. Symptoms ranged from mild to severe and were unrelated to dementia and chorea. CONCLUSIONS: Neuropsychiatric symptoms are prevalent in Huntington's disease and are relatively independent of cognitive and motor aspects of the disease. Hypothesised links between neuropsychiatric symptoms of Huntington's disease and frontal-striatal circuitry were explored. Findings indicate that dimensional measures of neuropsychiatric symptoms are essential to capture the full range of pathology in Huntington's disease and are vital to include in a comprehensive assessment of the disease.

Fuh JL, Liu CK, Mega MS, Wang SJ, Cummings JL. · Neurological Institute, Veterans General Hospital-Taipei, National Yang-Ming University Schools of Medicine, Taiwan. · Int Psychogeriatr. · Pubmed #11352329 No free full text.

Abstract: OBJECTIVES: To evaluate the applicability of the Chinese version of the Neuropsychiatric Inventory Scale (NPI), and to explore the neuropsychiatric manifestations of Taiwanese patients with Alzheimer's disease (AD) and caregiver distress. METHOD: The Mini-Mental State Examination (MMSE) was administered to 95 patients with AD, and their caregivers were interviewed with the NPI. To assess the test-retest reliability of the Chinese version of the NPI, 86 caregivers underwent a second NPI 3 weeks later. RESULTS: The Cronbach's alpha coefficient of the Chinese version of the NPI was .76. The test-retest reliabilities of frequency, severity, and caregiver burden scores were significantly correlated; overall correlations were .85 for frequency (p < .001), .82 for severity (p < .001), and .79 (p < .001) for distress. Factor analysis was carried out, and three groups, "mood and psychosis," "psychomotor regulation," and "social engagement," were found. Aberrant motor behavior was the most frequently recorded behavior; euphoria was the least. There was no significant correlation between the patient's MMSE and the caregiver distress score, except for aberrant motor activity (r = -.23, p = .03). The symptoms most frequently reported to be severely distressing to caregivers were aberrant motor activity, anxiety, agitation, and delusions. CONCLUSIONS: These results indicate that the NPI is a reliable tool to assess behavioral disturbance and caregiver distress in Taiwanese AD patients. These findings also confirm the high prevalence of psychopathology among AD patients and the marked distress produced by many of these behaviors.

Wood S, Cummings JL, Hsu MA, Barclay T, Wheatley MV, Yarema KT, Schnelle JF. · Department of Psychology, Scripps College, Claremont, California 91711-3948, USA. · Am J Geriatr Psychiatry. · Pubmed #10648298 No free full text.

Abstract: The authors assessed the validity of the nursing home version of the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), comparing the responses of certified nurses' aides (CNAs) and licensed vocational nurses (LVNs) with research observations. Correlations were significant but moderate for all of the domains of the NPI-NH (delusions, hallucinations, agitation/aggression, depression, apathy, disinhibition, euphoria, irritability/lability, and aberrant motor disturbances) except anxiety and appetite disturbance. The LVNs' ratings showed consistently higher correlations with the researchers' behavioral observations than did the CNAs', but were moderate and generally better for residents with high levels of neuropsychiatric symptoms, thus, caution should be used with any untrained rater in the nursing home setting. The NPI-NH used by non-research staff can be useful in identifying residents with significant neuropsychiatric disturbances, but may be limited as an instrument for tracking behavioral changes.

Mega MS, Masterman DM, O'Connor SM, Barclay TR, Cummings JL. · Laboratory of Neuro Imaging, Alzheimer's Disease Research Center, University of California, Los Angeles, School of Medicine, 90095-1769, USA. · Arch Neurol. · Pubmed #10555660 links to  free full text

Abstract: BACKGROUND: Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources. OBJECTIVE: To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride. METHODS: Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (> or =4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change), or nonresponder (> or =4-point total NPI score increase, indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response. RESULTS: Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04), depression (P = .006), anxiety (P = .02), apathy (P = .003), disinhibition (P = .02), and irritability (P<.001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 for responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group. CONCLUSIONS: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.

Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, Cummings JL. · Section of Geriatric Psychiatry, Rogaland Psychiatric Hospital, Stavanger, Norway. · J Neurol Neurosurg Psychiatry. · Pubmed #10486397 links to  free full text

Abstract: OBJECTIVES: Disturbances of cognition and emotion are common in patients with Parkinson's disease. Most previous studies of psychopathology in Parkinson's disease have focused on a single psychiatric diagnosis or condition. The objective of this study was to describe the range of neuropsychiatric symptoms in a representative sample of patients with Parkinson's disease. METHODS: The sample of 139 patients was drawn from an epidemiological study of Parkinson's disease in Rogaland county, Norway, and represented 93% of those who had survived during the 4 years since the initial assessment. The diagnosis of Parkinson's disease was based on published criteria. Neuropsychiatric symptoms were assessed using the neuropsychiatric inventory, a caregiver based structured interview, which assesses severity and frequency of 10 psychiatric symptoms present during the past month. RESULTS: At least one psychiatric symptom was reported in 61% of the sample. The most common behaviours were depression (38%) and hallucinations (27%), and the least common symptoms were euphoria and disinhibition. The highest mean scores were found for depression, apathy, and hallucinations. Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor, and apathy and anxiety constituted another factor. Psychiatric symptoms were more common among patients living in nursing homes compared with home dwelling patients, and correlated with stage of disease and cognitive impairment, but not with age or duration of disease. No relation to left or right sided parkinsonism was found. CONCLUSION: This study emphasises the importance of psychiatric symptoms in Parkinson's disease, which were present in most patients. Clinicians should focus on the emotional and cognitive disturbances in addition to the motor manifestations of the disease.