Multiple system atrophy presenting with language impairment.
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Humans↗
Biomedical subjects
J L Cummings
Publications and source records attributed to J L Cummings.
Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress.
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.
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Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia.
OBJECTIVE: To explore the neuropsychiatric manifestations in patients with Alzheimer's disease (AD) and cortical and subcortical vascular dementia (VaD). METHODS: We investigated consecutive patients with dementia. All the participants received brain computed tomography. The diagnosis of dementia was confirmed by clinical criteria and the imaging findings. Only patients with probable AD, and subcortical and cortical VaD were included. The Mini Mental State Examination (MMSE) was used to evaluate global cognitive function, and the Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. RESULTS: Of the 536 participants with dementia, 320 (59.7%) had AD, 161 (30%) had subcortical VaD, 35 (6.4%) had cortical VaD, and 16 (2.9%) had mixed cortical and subcortical VaD. Cortical VaD patients had the highest mean composite NPI scores in all domains and AD patients had the lowest composite scores in most domains. The mean composite scores of the apathy and sleep disturbance domains in patients with cortical VaD were significantly higher than those in the patients with AD after controlling for years of education and MMSE score (p < 0.01). CONCLUSIONS: There were few differences among the patients with AD, subcortical VaD and cortical VaD. The most consistent differences were the high sleep disturbance scores in those with cortical VaD.
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Cholinesterase inhibitors for treatment of dementia associated with Parkinson's disease.
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Cholinesterase Inhibitors↗
[Neuropsychiatric Inventory-Nursing Home version (NPI-NH): Spanish validation].
INTRODUCTION: The Neuropsychiatric Inventory-Nursing Home version (NPI-NH) is a screening instrument to be used by the nursing staff to evaluate neuropsychiatric symptoms in dementia patients in the nursing home setting. The aim of the present study was to validate the NPI-NH in Spanish. METHODS: We assessed the validity of the NPI-NH in 80 patients who were also nursing home residents, comparing the responses of nursing home staff on the NPI-NH with that filled out by the external observer. We developed a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and both NPI-NH. We determined the concurrent validity of the domains "depression" and "agitation/aggression" of the NPI-NH with the Cohen-Mansfield Agitation Inventory (IAACM, Spanish version) and the Hamilton Depression Rating Scale (HDRS). RESULTS: Among the totals of the NPI-NH of the nursing staff and the NPI-Q, the convergent validity was r = 0.536 and r = 0.669 for the occupational disruptiveness scale (distress in NPI-Q). The Pearson correlation index between the NPI-Q and NPI-NH of the observations was r = 0.342. The convergent validity between the NPINH of the nursing home staff and NPI-NH of the observers with the Pearson correlation index was r = 0.274. CONCLUSIONS: The NPI-NH Spanish version offers the possibility to use a screening tool for detecting neuropsychiatric symptoms in dementia patients in the nursing home setting. It should be administered by adequately trained staff to avoid limitations in the evolutive control of behavioral changes.
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Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.
OBJECTIVES: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer's disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. METHODS: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer's Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. RESULTS: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. CONCLUSION: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.
Activities of Daily Living↗
Possible association of the tau H1/H1 genotype with primary progressive aphasia.
The authors screened for tau gene mutations and polymorphisms to determine whether genetic variation at or near the tau locus contributes to the development of primary progressive aphasia (PPA). No mutations were detected in 25 patients with PPA. However, a significant overrepresentation of the tau H1/H1 genotype, also found in progressive supranuclear palsy and corticobasal degeneration, was found in the PPA group. Whether tau haplotypes have a primary causal role or whether they affect the topology of neurodegeneration remains to be determined.
Adult↗
Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD.
OBJECTIVE: To assess the ability of the current diagnostic criteria for frontotemporal lobar degeneration (FTLD) to differentiate FTLD from AD. METHODS: Thirty cases with autopsy-proven FTLD and 30 cases of AD, matched for Mini-Mental State Examination score, were identified from the clinical databases of three dementia subspecialty centers, and their charts were reviewed for the presence of clinical features described in the current criteria for FTLD. The proportion of patients with each clinical feature at the first clinical presentation was compared across groups. RESULTS: A significantly larger proportion of patients with FTLD showed behavioral abnormalities, particularly social and personal conduct disorders and emotional blunting, than patients with AD. Few differences in language features were seen between the groups, and many of the language features detailed in the criteria were found in only a small proportion of patients. In both groups, many patients showed neuropsychological abnormalities, except for perceptual difficulties, which were present in many patients with AD but only in a few patients with FTLD. Extrapyramidal motor symptoms were more likely to be present in FTLD. Logistic regression revealed that five features-social conduct disorders, hyperorality, akinesia, absence of amnesia, and the absence of a perceptual disorder-correctly classified 93% of patients with FTLD and 97% of patients with AD. CONCLUSION: A combination of behavioral, neuropsychological, and physical findings is most useful in distinguishing FTLD from AD. Future studies should be directed at establishing more objective methods of identifying these clinical features.
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Endogenous estradiol in elderly individuals: cognitive and noncognitive associations.
OBJECTIVE: To investigate an association between endogenous estradiol (E(2)) levels and cognition and behavior in elderly individuals. PATIENTS: We studied 135 community-based men and women aged 52 to 85 years in urban Bangkok, Thailand; 72 had dementia and 63 did not. MATERIALS AND METHODS: Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria after appropriate investigations. Blood samples for assay were collected in the morning after 6 hours of fasting. Levels of E(2) were measured by radioimmunoassay (double antibody technique). The Thai version of the Mini-Mental State Examination was used to assess cognition; the Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms; and the Functional Assessment Questionnaire was used to assess instrumental activities of daily living. RESULTS: There was no correlation between age and level of E(2) in either men or women. Individuals with lower estrogen levels had more behavioral disturbances (men: r = -0.467, n = 45; P =.001; women: r = -0.384, n = 90; P<.001) and worse cognition (men: r = 0.316, n = 45; P =.03; women: r = 0.243, n = 90; P =.02) and function (men: r = -0.417, n = 45; P =.004; women: r = -0.437, n = 90; P<.001). The threshold level of endogenous E(2) in elderly individuals for the risk of developing dementia was less than 15 pg/mL (<55 pmol/L) in men and less than 1 pg/mL (<4 pmol/L) in women. CONCLUSION: Lower E(2) levels are correlated with poor cognitive, behavioral, and functional status in older individuals.
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Neuropsychiatric symptoms of Alzheimer's disease differ in Chinese and American patients.
BACKGROUND: The prevalence of Alzheimer's disease is similar across ethnic groups. To our knowledge, no comparison of behavioral symptoms has been addressed. OBJECTIVE: This cross-sectional, retrospective, descriptive study compares neuropsychiatric symptoms of Chinese subjects with Alzheimer's disease (AD) at tertiary care centers in Taiwan and Hong Kong against Caucasian subjects in Los Angeles, California. We compared the frequency and severity of symptoms and caregiver responses to neuropsychiatric symptoms of AD using the Neuropsychiatric Inventory (NPI). We hypothesized that Chinese patients do not seek care unless they have high severity of neuropsychiatric symptoms and that Caucasian Americans do not wait for behavioral disturbances to develop before coming to medical attention. RESULTS: The Caucasian sample had the highest mean educational level and mildest Clinical Dementia Rating (CDR) scale distributions of all four groups. Older age and lower educational levels contributed to higher CDR scale scores, which in turn correlated with higher total NPI scores. Only one of the Chinese samples had a higher frequency of severe neuropsychiatric symptoms than the Caucasian sample. Chinese caregivers reported anxiety and delusions more frequently (58.1%) than Caucasians (37.3% and 39.6%; chi(2), p < 0.01 and p < 0.05, respectively). Caucasians reported appetite changes (47.3%) and apathy (59.2%) more frequently than the Chinese samples (chi(2), p < 0.05 and p < 0.01, respectively). Caregivers at all four centers were distressed by behaviors qualified as severe. CONCLUSION: We found support for our hypothesis, in that Chinese subjects presented during a more severe stage of dementia than American subjects, but the delay in seeking care could not be correlated with significant differences in neuropsychiatric profiles of the demented subjects. Other barriers to dementia care warrant investigation.
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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.
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Depression in Parkinson's disease.
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Depressive Disorder↗
A transcultural study of agitation in dementia.
Agitation is one of the most troublesome behaviors in demented patients. It is etiologically heterogeneous and has varied associated behaviors. To explore the transcultural differences in the manifestation of agitation, we evaluated 50 consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy, and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE). In a focused analysis, only patients with composite NPI scores > 2 for agitation were selected, with similar levels of disease severity as measured by the MMSE, from the three groups (n = 15 per group) to evaluate culturally specific correlates of agitation. Agitated Taiwanese had significantly more hallucinations than either Italian or American patients. Agitated Italian patients had significantly more apathy than both Taiwanese and American patients. Cultural factors may influence the manifestation of agitation more than a common underlying neuropathology. Management strategies targeting unique behavioral instigators of agitation may be specific for different ethnic groups.
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Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.
CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.
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Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review) [RETIRED]. Report of the Quality Standards Subcommittee of the American Academy of Neurology.
OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.
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Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.
OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.
Dementia↗
Practice parameter: management of dementia (an evidence-based review) [RETIRED]. Report of the Quality Standards Subcommittee of the American Academy of Neurology.
OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).
Dementia↗
Neuropsychiatric differences between Parkinson's disease with dementia and Alzheimer's disease.
OBJECTIVE: To compare the profile of neuropsychiatric symptoms in patients with Parkinson's disease with dementia (PDD) and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional survey of a population-based sample of patients with PDD and AD patients matched for age, sex, and Mini-Mental State Examination (MMSE) score. METHOD: Patients were diagnosed according to published criteria for PD and AD. The diagnosis of dementia in PD was made according to DSM-III-R, and was based on clinical interview of the patient and a relative, psychometric testing (including MMSE, Dementia Rating Scale and tests assessing memory, executive functions and visuospatial functioning) and physical examination. The Neuropsychiatric Inventory (NPI) was administered to all patients. RESULTS: One or more psychiatric symptoms was reported in 95% of AD and 83% of PDD patients. Hallucinations were more severe in PD patients, while aberrant motor behavior, agitation, disinhibition, irritability, euphoria, and apathy were more severe in AD. In PDD, apathy was more common in mild Hoehn and Yahr stages, while delusions increased with more severe motor and cognitive disturbances. In PDD, only delusions correlated with the MMSE score. CONCLUSIONS: Neuropsychiatric symptoms are common and severe in patients with PDD, with important implications for the management of these patients. AD and PDD patients have different neuropsychiatric profiles, suggesting different underlying mechanisms. Cognitive impairment, psychopathology, and motor features progress independently in PDD patients
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