Alzheimer Disease: Alexopoulos GS

Alexopoulos GS. · No affiliation provided · Am J Psychiatry. · Pubmed #18593780 links to  free full text

This publication has no abstract.

Alexopoulos GS. · No affiliation provided · Am J Psychiatry. · Pubmed #12727680 links to  free full text

This publication has no abstract.

Alexopoulos GS, Jeste DV, Chung H, Carpenter D, Ross R, Docherty JP. · No affiliation provided · Postgrad Med. · Pubmed #17203561 No free full text.

Abstract: OBJECTIVES: New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998. While only 2 cholinesterase inhibitors, donepezil and tacrine, were available in 1998, 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants. However, there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments. We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia. METHODS: Based on a literature review, a 61-question survey was developed with 1,225 options. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, the experts were asked to write in answers. The survey was sent to 50 North American experts on dementia, 100% of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. Based on the 95% confidence interval around the mean, we assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option. Guidelines indicating preferred treatment strategies were then developed for selected clinical situations. RESULTS: For patients at risk for dementia, the experts recommended control of hypertension and diabetes. They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia. Cholinesterase inhibitors were an option for patients with mild cognitive impairment (i.e., at risk for Alzheimer's dementia [AD]). To slow cognitive impairment in mild/moderate AD, the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and galantamine were the preferred cholinesterase inhibitors. The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate (NMDA) antagonist (e.g., memantine) if a patient with mild/moderate dementia has an inadequate response to monotherapy. Control of hypertension and diabetes was the treatment of choice, in patients with mild/moderate vascular or mixed AD/vascular dementia, with aspirin another first-line option. Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia. Among nonpharmacological interventions for mild/moderate dementia, the experts recommended caregiver education, supportive therapy for caregivers, referral to day treatment, exercise programs, and respite care. For moderate/severe AD or mixed AD/vascular dementia, the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor. For moderate/severe vascular or mixed AD/vascular dementia, they recommended control of hypertension and diabetes. The experts' ratings underscore the importance of nonpharmacological strategies aimed at reducing caregiver burden in more severe dementia. Management of agitation and other behavioral disturbances was another focus of this study. The experts recommended using an atypical antipsychotic for agitation associated with delirium, psychosis, aggression, or anger. They would also consider divalproex to manage anger with a risk of physical aggression. Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia. Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety. Trazodone was recommended for insomnia. The experts also gave recommendations concerning dosage levels, duration of treatment, and choice of medications for patients with different complicating conditions. CONCLUSIONS: The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances. Within the limits of expert opinion and with the expectation that new research data will take precedence, these guidelines may provide direction for clinicians offering care to patients with dementia.

Olin JT, Schneider LS, Katz IR, Meyers BS, Alexopoulos GS, Breitner JC, Bruce ML, Caine ED, Cummings JL, Devanand DP, Krishnan KR, Lyketsos CG, Lyness JM, Rabins PV, Reynolds CF, Rovner BW, Steffens DC, Tariot PN, Lebowitz BD. · Adult and Geriatric Treatment and Preventive Interventions Research Branch, National Institute of Mental Health, Bethesda, MD 20892-9635, USA. · Am J Geriatr Psychiatry. · Pubmed #11925273 No free full text.

Abstract: The authors, a group of investigators with extensive research and clinical experience related to both late-life depression and Alzheimer disease (AD), propose provisional affective and behavioral inclusion and exclusion diagnostic criteria for Depression of AD.

Kiosses DN, Klimstra S, Murphy C, Alexopoulos GS. · Weil College of Medicine, Cornell University, Ithaca, NY, USA. · Am J Geriatr Psychiatry. · Pubmed #11481135 No free full text.

Abstract: The authors studied 126 elderly patients without dementia and with unipolar major depression. Impairment in instrumental activities of daily living (IADLs) was significantly associated with age (P<0.0001), gender (P<0.001), medical burden (P=0.013), severity of depression (P=0.01), initiation/perseveration (IP; P=0.035), and IP x depression (P=0.029). Depression was associated with IADL impairment mainly in patients with impaired IP. Among the cognitive impairments, IP-only contributed significantly to IADL impairment, whereas attention, construction, conceptualization, and memory did not. Attention to executive function and disability may guide clinical management and lead to development of innovative pharmacological and behavioral interventions.

Kiosses DN, Alexopoulos GS, Murphy C. · Weill Medical College of Cornell University, USA. · Int J Geriatr Psychiatry. · Pubmed #11113977 No free full text.

Abstract: OBJECTIVE: To examine whether symptoms of striatofrontal dysfunction contribute to disability in geriatric depression. DESIGN: Cross-sectional evaluation of the relationship of specific cognitive impairments, psychomotor retardation, severity of depression, and medical burden to impairment of instrumental activities of daily living. SETTING: Inpatient and outpatient services of a psychiatric university hospital located in a suburban metropolitan area.Patients. One hundred and fifty elderly psychiatric inpatients and outpatients with major depression and cognitive function ranging from normal to moderate dementia. MEASURES: Psychomotor retardation was evaluated with the Hamilton retardation item and executive dysfunction was assessed with the initiation/perseveration (IP) domain of the Dementia Rating Scale. Disability, severity of depression and medical burden were assessed with the Instrumental Activities of Daily Living Index of the Multilevel Assessment Instrument, the Hamilton Depression Rating Scale and the Cumulative Illness Rating Scale-Geriatric, respectively. RESULTS: In the entire sample (N = 150) and in the non-demented subjects (N = 101), stepwise regression analyses revealed that IP and psychomotor retardation were associated with IADL impairment. Additionally, a 'striatofrontal component', which consisted of IP and psychomotor retardation was also significantly associated with IADL impairment in the whole sample, as well as in the non-demented patients. CONCLUSION: Clinical symptoms and neuropsychological findings associated with striatofrontal dysfunction contribute to disability in depressed elderly patients.