Alzheimer Disease: Brodaty H

Brodaty H, Dresser R, Eisner M, Erkunjuntti T, Gauthier S, Graham N, Jonker C, Sachs G, Whitehouse P. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10372949 No free full text.

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Whitehouse PJ, Arizaga R, Brodaty H, Gauthier S, Graham N, Green RC, Homma A, Mangone C, Senanarong V, Xu XH. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10485568 No free full text.

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Draper B, Brodaty H, Low LF. · School of Psychiatry, University of NSW, Sydney, Australia. · Int J Geriatr Psychiatry. · Pubmed #16802279 No free full text.

Abstract: BACKGROUND: Previous models of mental health care for older persons have not considered the full spectrum of mental disorders. AIM: To describe a tiered model for comprehensive evidence-based planning of service delivery for mental disorders in late life. METHOD: The model depicts tiers of mental disorders in ascending order of severity and consequent interventions required. RESULTS: Interventions aim both to avert individuals from moving up tiers (prevention) and to move individuals down tiers (treatment). Individuals in the lower tiers have no mental disorders and prevention strategies are targeted at known risk factors. In the middle tiers, individuals with mild-moderate mental disorders will mainly be treated in primary care, often in collaboration with specialist mental health services for older people. Individuals in the top tiers with severe mental disorders usually require institutional care. CONCLUSION: The tiered model provides a basis for planning comprehensive service delivery.

Berman K, Brodaty H. · Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. · CNS Drugs. · Pubmed #15377170 No free full text.

Abstract: In this article, we review the evidence that tocopherol (vitamin E) may have a role to play in the prevention and treatment of Alzheimer's disease and other neurological diseases. The theoretical rationale for the effectiveness of tocopherol as treatment and/or prevention of Alzheimer's disease is based on its antioxidant properties. Results from animal and in vitro studies provide evidence to support use of tocopherol for prevention and treatment of degenerative neurological diseases. Furthermore, several, but not all, epidemiological, cross-sectional, prospective studies indicate that tocopherol may have protective effects in Alzheimer's disease, although dietary and supplemental forms of the vitamin may differ in their efficacy. Mixed results have been obtained from clinical trials. Evidence of the use of tocopherol as a protective measure or as therapy in neurological diseases other than Alzheimer's disease is less compelling. To date, there are no clear-cut answers as to whether tocopherol is worth prescribing, but current clinical practice favours its use in the treatment of Alzheimer's disease.

Brodaty H, Green A. · Academic Department for Old Age Psychiatry, Prince of Wales Hospital, School of Psychiatry, University of New South Wales. · Aust Fam Physician. · Pubmed #12402702 No free full text.

Abstract: BACKGROUND: Dementia not only affects the patient but also those nearest the patient most notably the carer. It is known that caring for a patient with dementia can adversely affect one's psychological, physical, social and financial health. OBJECTIVE: To highlight the needs of the carer of a patient with dementia and suggest means by which general practitioners may provide the necessary support for these carers. DISCUSSION: The GP has a key role in providing support to the carer of the patient with dementia. General practitioners and carers can work as partners in the long term management of dementia thereby reducing the adverse health effects on the carer.

Brodaty H, Ames D, Boundy KL, Hecker J, Snowdon J, Storey E, Yates MW. · School of Psychiatry, University of New South Wales, and Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Sydney. · Med J Aust. · Pubmed #11665948 No free full text.

Abstract: Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women.

Winblad B, Brodaty H, Gauthier S, Morris JC, Orgogozo JM, Rockwood K, Schneider L, Takeda M, Tariot P, Wilkinson D. · Karolinska Institutet, Alzheimer Research Center, Huddinge University Hospital, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #11466744 No free full text.

Abstract: The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.

Monk D, Brodaty H. · Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Sydney, N.S.W., Australia. · Dement Geriatr Cogn Disord. · Pubmed #10629355 No free full text.

Abstract: This review examines the biological rationale for the use of estrogen replacement therapy (ERT) and the evidence for the efficacy of ERT in enhancing cognition, preventing Alzheimer's disease (AD) and treating AD in postmenopausal women. While the biological basis for ERT as a cognition enhancer is strong and multiply mediated, the clinical evidence for its use is not as compelling and must be weighed against possible side effects. Until the results of definitive large trials are available, the use of ERT alone or in combination with other treatments is worthy of consideration.

Brodaty H. · Academic Department of Psychogeriatrics, Prince of Wales Hospital, Randwick, New South Wales, Australia. · Eur Neuropsychopharmacol. · Pubmed #10332934 No free full text.

Abstract: Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized clinically by cognitive and functional deficits and behavioural disturbances. Over the past two decades, the devastating nature of AD has captured the attention of the general and medical communities alike. This is due partly to the increased prevalence of AD and the expansion of the aged population. Furthermore, and perhaps inappropriately, the media have encouraged speculation concerning a 'cure' for AD. Such treatment strategies are in the early stages of pre-clinical investigation and well-designed clinical trials are awaited. Nevertheless, other strategies, aimed at reducing the progression or effects through pharmacological symptomatic therapies and psychosocial interventions have demonstrated some clinical benefit and are now available and practicable. This paper critically evaluates the merits of both currently available and potential future therapeutic strategies according to primary, secondary and tertiary levels of preventative treatment.

Brodaty H, Woodward M, Boundy K, Barnes N. · No affiliation provided · CNS Drugs. · Pubmed #17381186 No free full text.

This publication has no abstract.

Brodaty H, Woodward M, Boundy K, Barnes N, Allen G, Anonymous00121. · Academic Department for Old Age Psychiatry, School of Psychiatry, University of New South Wales and Prince of Wales Hospital, Randwick, NSW, Australia. · CNS Drugs. · Pubmed #17044730 No free full text.

Abstract: OBJECTIVE: To collect descriptive data on the treatment of Alzheimer's disease with galantamine under naturalistic conditions. STUDY DESIGN: This was a prospective, open-label, observational study. PATIENTS: Subjects (n = 345) with mild to moderately severe dementia of the Alzheimer's type were recruited from 48 hospitals in Australia. METHODS: Subjects were enrolled and received treatment with galantamine for 6 months in a clinical practice setting. Subjects were assessed at baseline and 3 and 6 months after starting treatment using the Mini-Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [the latter only if the baseline MMSE score was at least 25]. Subjects were also assessed using an abridged Instrumental Activities of Daily Living (IADL) questionnaire that included questions on using the telephone, ability to travel more than 1km outside the home, taking medications and managing money, and an 11-item behaviour assessment scale that measured aggression, sleep disturbance, disinhibition, personality changes, irritability, depression, agitation, apathy, inertia, hallucinations and aberrant motor behaviour. RESULTS: Of the 345 subjects who were enrolled in the study (intent-to-treat [ITT] population), 229 completed the baseline, 3- and 6-month visits (per-protocol [PP] population). The mean age of the PP population was 78.0 +/- 6.8 years.At 6 months, most PP subjects (70%) showed an increase in MMSE score compared with baseline, with a mean increase in score of 2.0 +/- 3.1 points from a baseline of 20.8 +/- 4.2 points. In the ITT population, 44% of subjects (151/345) showed an increase in MMSE after 6 months. If data were unavailable the patient was classified as a nonresponder. Of the 21 PP patients who were assessed using ADAS-cog, 18 (86%) demonstrated a decrease in the ADAS-cog score, reflecting an improvement in cognition. Of the ITT population, 33% (19/57) had a decreased ADAS-cog score after 6 months.Most PP subjects (86%) were considered responders according to the CIBIC-plus score, with 65% showing some improvement over 6 months of treatment. Of the ITT population, 54% (187/345) showed no deterioration in CIBIC-plus score after 6 months.No deterioration in IADL or behaviour assessments occurred in the majority of PP subjects over 6 months. CONCLUSIONS: In a clinical practice setting, the majority of subjects receiving galantamine who completed the study maintained their ratings of cognition, function, behaviour or global assessment over the 6-month period.

Brodaty H, Corey-Bloom J, Potocnik FC, Truyen L, Gold M, Damaraju CR. · University of New South Wales, Sydney, Australia. · Dement Geriatr Cogn Disord. · Pubmed #15990426 No free full text.

Abstract: The primary objective of this study was to evaluate the efficacy and tolerability of a flexible dosing regimen (16 or 24 mg/day) of galantamine prolonged-release capsule (PRC) compared with placebo in subjects with mild to moderate Alzheimer's disease (AD). This phase III, double-blind, placebo- and active-controlled, parallel-group trial randomized 971 patients to treatment for 6 months. Efficacy endpoints included change in the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scores. Galantamine was associated with significant improvements in the ADAS-cog/11 score but not in the CIBIC-plus or NPI scores. Galantamine PRC was associated with significant improvement in ADCS-ADL scores. Galantamine PRC had similar tolerability and safety profiles compared with twice-daily galantamine, and when administered as a once-daily flexible dosing regimen of 16 or 24 mg/day, was demonstrated to be as safe and effective for the treatment of mild to moderate AD.

Ross AJ, Sachdev PS, Wen W, Valenzuela MJ, Brodaty H. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Neurobiol Aging. · Pubmed #15718046 No free full text.

Abstract: The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.

Kleinman L, Frank L, Ciesla G, Rupnow M, Brodaty H. · MEDTAP International, Inc,, 2601 4th Ave, Seattle, WA 98121, USA. · Health Qual Life Outcomes. · Pubmed #15535887 links to  free full text

Abstract: BACKGROUND: Multiple instruments exist to measure dementia behaviors, but the nursing staff perspective on those behaviors and their level of burden has not been well measured. The goal of this study was to examine the psychometric performance of the Modified Nursing Care Assessment Scale (M-NCAS), a 28-item nurse rating of burden associated with care for institutionalized individuals with dementia. Nurses rate items in terms of extent to which the behavior or characteristic is present ("attitude" domain), and extent to which it is a burden ("strain" domain). METHODS: Data from 282 patients enrolled in a 12-week, double-blind, randomized clinical trial comparing risperidone treatment to placebo was used to evaluate M-NCAS item performance, internal consistency reliability, and construct validity. Empirical subscales were identified via exploratory factor analysis (EFA). RESULTS: Four poorly-performing items were deleted from further analyses. EFA identified 3 "attitude" subscales and 5 "strain" subscales. Cronbach's alphas were 0.65 and above. Correlation with the Cohen-Mansfield Agitation Inventory and the BEHAVE-AD, clinical ratings of dementia behaviors, were low to moderate. CONCLUSION: The M-NCAS provides a valid and reliable means of obtaining care burden ratings from formal caregivers in long-term care, and provides a method for evaluating dementia interventions from the perspective of nursing staff.

Rabinowitz J, Katz IR, De Deyn PP, Brodaty H, Greenspan A, Davidson M. · Bar Ilan University, Ramat Gan, Israel. · J Clin Psychiatry. · Pubmed #15491235 No free full text.

Abstract: OBJECTIVE: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD). METHOD: We conducted a post hoc exploratory analysis of an integrated database from 3 randomized, controlled trials of risperidone versus placebo in treating 1150 nursing home residents with BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). RESULTS: On the CMAI, risperidone was significantly more effective in treating hitting (p = .000), hurt self or other (p = .005), cursing or verbal aggression (p = .000), repetitive sentences or questions (p = .001), scratching (p = .041), general restlessness (p = .001), grabbing onto people (p = .028), constant request for attention (p = .041), pacing and aimless wandering (p = .013), and performing repetitious mannerisms (p = .045). On the BEHAVE-AD, risperidone was significantly more effective in treating physical threats and/or violence (p = .000), verbal outbursts (p = .000), other anxieties (p = .01), agitation (p = .000), tearfulness (p = .03), and nonparanoid delusions (p = .02). CONCLUSIONS: The items from the BEHAVE-AD and CMAI that were improved with risperidone included psychotic, agitated, and aggressive symptoms. These data suggest that risperidone is more effective than placebo in treating a variety of symptoms associated with dementia.

Brodaty H, Ames D, Snowdon J, Woodward M, Kirwan J, Clarnette R, Lee E, Lyons B, Grossman F. · Academic Department for Old Age Psychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia. · J Clin Psychiatry. · Pubmed #12633121 No free full text.

Abstract: BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. METHOD: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. RESULTS: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. CONCLUSION: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.

Ashford JW, Borson S, O'Hara R, Dash P, Frank L, Robert P, Shankle WR, Tierney MC, Brodaty H, Schmitt FA, Kraemer HC, Buschke H. · Stanford / VA Alzheimer Center, Department of Psychiatry, Palo Alto VA Health Care System, Palo Alto, CA, USA. · Alzheimers Dement. · Pubmed #19595860 No free full text.

Abstract: The question of whether to screen for dementia and Alzheimer's disease (AD) has been discussed in many forums throughout the world. Generally, medical advisory groups and policy-making groups have recognized the importance of early diagnosis but have uniformly avoided making recommendations to screen at-risk populations. This presentation reflects the support for reconsidering the importance of screening individuals at risk or above a certain age. In this statement, the majority of the authors support the consideration of dementia risk factors in individuals at age 50, with routine yearly screening after 75. Other authors remain concerned that the benefits of treatments of early disease do not yet support a general screening recommendation. These statements are made to encourage progress toward the development of a consensus regarding the widespread institution of screening policy. Accordingly, members of the worldwide scientific community are invited to add their perspective by contributing short commentaries (1500 words) on this subject.

Ballard CG, Gauthier S, Cummings JL, Brodaty H, Grossberg GT, Robert P, Lyketsos CG. · King's College London, London, UK. · Nat Rev Neurol. · Pubmed #19488082 No free full text.

Abstract: Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Mittelman MS, Brodaty H, Wallen AS, Burns A. · Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. · Am J Geriatr Psychiatry. · Pubmed #18978250 No free full text.

Abstract: OBJECTIVE: To evaluate the effectiveness of a combination of cholinesterase inhibitor therapy for patients with Alzheimer disease (AD) and psychosocial intervention, for their spouse caregivers compared with drug treatment alone in three countries simultaneously. DESIGN: Randomized controlled trial. Structured questionnaires were administered at baseline and at regular follow-up intervals for 24 months by independent raters blind to group assignment. SETTING: Outpatient research clinics in New York City, U.S., Manchester, U.K. and Sydney, Australia. PARTICIPANTS: Volunteer sample of 158 spouse caregivers of community dwelling patients with AD. INTERVENTIONS: Five sessions of individual and family counseling within 3 months of enrollment and continuous availability of ad hoc telephone counseling were provided for half the caregivers. Donepezil was prescribed for all patients. MAIN OUTCOME MEASURE: Depressive symptoms of spouse caregivers measured at intake and follow-up assessments for 24 months using Beck Depression Inventory (revised). RESULTS: Depression scores of caregivers who received counseling decreased over time, whereas the depression scores for caregivers who did not receive counseling increased. The benefit of the psychosocial intervention was significant after controlling for site, gender and country was not accounted for by antidepressant use and increased over 2 years even though the individual and family counseling sessions occurred in the first 3 months. CONCLUSION: Effective counseling and support interventions can reduce symptoms of depression in caregivers when patients are taking donepezil. Harmonized multinational psychosocial interventions are feasible. Combined drug and supportive care approaches to the management of people with AD should be a priority.

Henry JD, Ruffman T, McDonald S, O'Leary MA, Phillips LH, Brodaty H, Rendell PG. · School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia. · Neuropsychologia. · Pubmed #18241898 No free full text.

Abstract: The neural substrates that subserve decoding of different emotional expressions are subject to different rates of degeneration and atrophy in Alzheimer's disease (AD), and there is therefore reason to anticipate that a differentiated profile of affect recognition impairment may emerge. However, it remains unclear whether AD differentially affects the recognition of specific emotions. Further, there is only limited research focused on whether affect recognition deficits in AD generalize to more ecologically valid stimuli. In the present study, relatively mild AD participants (n=24), older controls (n=30) and younger controls (n=30) were administered measures of affect recognition. Significant AD deficits were observed relative to both the younger and older control groups on a measure that involved labeling of static images of facial affect. AD deficits on this measure were observed in relation to all emotions assessed (anger, sadness, happiness, surprise and fear), with the exception of disgust, which was preserved even relative to the younger adult group. The relative preservation of disgust could not be attributed to biases in the choice of labels made, and it is suggested instead that this finding might reflect the relative sparing of the basal ganglia in AD. No significant AD effect was observed for the more ecologically valid measure that involved dynamic displays of facial expressions, in conjunction with paralinguistic and body movement cues, although a trend for greater AD difficulty was observed.

Nash S, Henry JD, McDonald S, Martin I, Brodaty H, Peek-O'Leary MA. · School of Psychology, University of New South Wales, Sydney 2052, Australia. · J Int Neuropsychol Soc. · Pubmed #17942023 No free full text.

Abstract: Individuals with Alzheimer's disease (AD) experience difficulties with socioemotional functioning, and it has been proposed that cognitive disinhibition may be one potential mechanism that contributes to difficulties in this area. To test this possibility, twenty individuals with AD and 20 demographically matched controls were administered self-report measures of depression, emotion regulation and empathy, in addition to a behavioral measure that has proven to be very sensitive to inhibitory failures (the Hayling Sentence Completion Test). Relative to controls AD participants exhibited increased inhibitory failures on the Hayling, and self-reported significantly reduced cognitive empathy, but did not differ with respect to affective empathy, depression or perceived capacity for emotion regulation. Controlling for general cognitive status, in the AD (but not the control) group, reduced cognitive inhibition was associated with lower levels of depression. The theoretical and practical implications of these results are discussed.

Brodaty H, Sachdev P, Berman K, Gibson L, Kemp NM, Cullen B, Burns A. · School of Psychiatry, University of New South Wales, Kensington, Australia. · Aging Ment Health. · Pubmed #17612809 No free full text.

Abstract: The objective of the study is to explore the longitudinal course of patients with Alzheimer's disease (AD) with and without extrapyramidal signs (EPS) taking donepezil. A cohort of 106 community-dwelling patients with probable AD receiving donepezil in Sydney, Australia (n = 52) and Manchester, UK (n = 54) was followed over 12 months. Cognition was measured by the Mini-Mental State Exam (MMSE) and the Alzheimer Disease Assessment Scale-Cognitive test (ADAS-Cog) and function by the Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). A further follow-up at five years was conducted to examine mortality and institutionalisation. At baseline, EPS were correlated with MMSE (r = -0.467, p < 0.01), ADAS-Cog (r = 0.485, p < 0.01) and ADCS-ADL (r = -0.526, p < 0.01) scores. Patients with EPS had lower MMSE (F = 9.95, df = 1, p = 0.002) and ADCS-ADL (F = 9.41, df = 1, p = 0.003) scores than patients without EPS. Over one year no time main effects or time x group interaction effects were observed for either dependent variable. At five years patients with EPS were found to have a hazard of institution or death 2.2 times higher than those without EPS (p = 0.018; 95% CI: 1.2, 4.4). There was a positive association between EPS and cognitive and functional impairment. However, EPS did not predict more rapid cognitive or functional decline of patients taking donepezil or response to donepezil. The presence of EPS was a risk factor both for institutionalisation and for death.

Anderson TM, Sachdev PS, Brodaty H, Trollor JN, Andrews G. · School of Psychiatry, University of New South Wales, the Clinical Research Unit for Anxiety and Depression, Darlinghurst, New South Wales, Australia. · Am J Geriatr Psychiatry. · Pubmed #17545447 No free full text.

Abstract: OBJECTIVE: This article examines the influence of sociodemographic, biological, and health variables on Mini-Mental State Exam (MMSE) performance, and assesses how the diversity of the population should be reflected in the MMSE cutoff scores used for screening. METHODS: The sociodemographic profiles and MMSE scores of adults aged 65-years and over who participated in the Australian National Mental Health and Well-being Survey were assessed (N = 1,792). RESULTS: The regression models showed that older age, education levels, language spoken at home and in country of birth, socioeconomic status (SES), occupation, sex, and presence of a mood disorder made significant and unique contributions to performance on the MMSE. The individual (univariate) influence of each factor ranged from -2.61 to 0.09 points, with non-English speaking background (NESB) making the biggest impact. Based on a MMSE score of < or =23 points, 7.7% of the Australian elderly population screened positive for cognitive impairment that may be indicative of dementia. In those scoring < or =23 points, the multivariate model accounted for 24.61% of the variance. CONCLUSION: Many sociodemographic variables and the presence of a mood disorder influence MMSE performance. Using conventional cutoff scores for screening will lead to a high rate of false positives in older adults (75+ years), those with NESB, and those with low SES, and is insensitive for those with high education. The authors suggest simple rules for the correction of the impact of these variables.

Sachdev PS, Chen X, Joscelyne A, Wen W, Altendorf A, Brodaty H. · School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia. · J Neurol Sci. · Pubmed #17482210 No free full text.

Abstract: BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.

Katz I, de Deyn PP, Mintzer J, Greenspan A, Zhu Y, Brodaty H. · Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA, and Department of Neurology, Memory Clinic, Middelheim Hospital, ZNA, Wilrijk-Antwerp, Belgium. · Int J Geriatr Psychiatry. · Pubmed #17471598 No free full text.

Abstract: BACKGROUND: Dementia typically includes behavioral and psychological symptoms of dementia (BPSD) as well as cognitive decline. Psychosis of Alzheimer's disease (AD) is a specific component of AD, characterized by delusions, misidentifications, and hallucinations. METHODS: This study is a meta-analysis of patients with psychosis of AD from four large placebo-controlled clinical trials of risperidone in dementia. Three trials included patients diagnosed with heterogeneous symptoms of BPSD (those with psychosis of AD were included in this analysis), while one trial included only those diagnosed with psychosis of AD. Efficacy was measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression (CGI). RESULTS: Primary analyses in the psychosis of AD population demonstrated that risperidone significantly improved scores on the BEHAVE-AD Psychosis subscale and CGI scale compared with placebo. Secondary analyses demonstrated that patients with more severe symptoms showed a more pronounced response to treatment with risperidone compared with placebo than those patients with less severe symptoms. Extrapyramidal symptoms and somnolence were more frequent with risperidone than placebo (p=0.04). Cerebrovascular adverse events and all-cause mortality were observed more frequently, although not statistically significantly, with risperidone versus placebo. CONCLUSIONS: This meta-analysis of psychosis of AD showed improvement in psychotic symptoms and general clinical improvement in patients with psychosis of AD treated with risperidone compared with placebo. The benefits of treatment were most significant in patients with severe symptoms. The safety profile of risperidone in this psychosis of AD population was similar to the more general BPSD population.