Alzheimer Disease: Aarsland D

McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M, Anonymous00346. · Institute for Ageing and Health, University of Newcastle upon Tyne, UK. · Neurology. · Pubmed #16237129 No free full text.

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Aarsland D, Londos E, Ballard C. · The Norwegian Centre for Parkinson's Disease, Stavanger University Hospital, Norway and Institute of Clinical Medicine, University of Bergen, Norway. · Int Psychogeriatr. · Pubmed #19173762 No free full text.

This publication has no abstract.

Aarsland D, Kurz M, Beyer M, Bronnick K, Piepenstock Nore S, Ballard C. · Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Dement Geriatr Cogn Disord. · Pubmed #18204253 No free full text.

Abstract: BACKGROUND: The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD). METHOD: We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. RESULTS: The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. CONCLUSION: Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Rongve A, Aarsland D. · Haugesund County Hospital, Haugesund, Norway University of Bergen, Bergen, Norway. · Drugs Aging. · Pubmed #17067184 No free full text.

Abstract: Parkinson's disease dementia (PDD) ultimately develops in about 80% of patients with Parkinson's disease (PD), and cross-sectional studies have found that some 30% of these patients will experience neuropsychiatric symptoms, such as visual hallucinations and psychosis. The most consistently reported risk factors for dementia in PD are age, severe parkinsonism and mild cognitive impairment. In PDD, both subcortical cognitive and cortical cognitive profiles are described. Specific disorders of sleep, such as rapid eye movement sleep behaviour disorder, excessive daytime sleepiness and sleep attacks, occur frequently. Alzheimer and Lewy body pathology coexist, but the Lewy body pathology in limbic and cortical areas seems to be the main cause of dementia. Neurochemical changes in the biogenic amines and acetylcholine are common, and magnetic resonance imaging studies have shown cortical atrophy in wide cortical areas, including the hippocampus. All PD patients should be screened for mild cognitive impairment and dementia. A large randomised clinical trial showed that the cholinesterase inhibitor rivastigmine has desirable effects on cognition and neuropsychiatric symptoms in PDD patients. Atypical antipsychotic agents may improve psychosis in PDD, but the evidence for this is poor and adverse effects from such therapy are common and may be severe. Non-pharmacological interventions can also be effective but require further study.

Aarsland D, Sharp S, Ballard C. · Centre for Clinical Neuroscience Research, Stavanger University Hospital, PO Box 1163, 4095 Stavanger, Norway. · Curr Neurol Neurosci Rep. · Pubmed #16131417 No free full text.

Abstract: Psychiatric and behavioral symptoms are common in all types of dementia and have important consequences for patients, caregivers, and society. This paper reviews recent studies of the etiology and management of these symptoms. Genetic and neurochemical studies indicate that cholinergic, serotonergic, and dopaminergic systems may influence the risk of psychiatric symptoms in patients with dementia. There is still no consensus regarding the management of such symptoms. Controlled studies of psychosocial interventions, usually performed in the nursing home setting, report encouraging results. Atypical antipsychotics may be effective in some cases but have a high risk of adverse events. There is emerging evidence that cholinesterase inhibitors may reduce and prevent such symptoms. More studies are needed to clarify the role of cholinergic and other psychotropic agents as well as nonpharmacologic interventions for psychiatric and behavioral symptoms in patients with dementia.

McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O'Brien J, Playfer J, Reid W, Anonymous00116. · Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #14693108 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second commonest cause of neurodegenerative dementia in older people. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. DLB has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's disease. Here we review the current state of scientific knowledge on DLB. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other common types of dementia. Severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality. Treatment with cholinesterase inhibitors is well tolerated by most patients and substantially improves cognitive and neuropsychiatric symptoms. Clear guidance on the management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life.

Skjerve A, Holsten F, Aarsland D, Bjorvatn B, Nygaard HA, Johansen IM. · Olaviken Treatment Center, University of Bergen, Bergen, Norway. · Psychiatry Clin Neurosci. · Pubmed #15298644 No free full text.

Abstract: Ten elderly subjects with severe dementia were given bright light (5000-8000 lux) for 45 min each morning for 4 weeks. Two rating scales of behavioral symptoms in dementia were used as outcome measures: Cohen-Mansfield Agitation Inventory (CMAI) and Behavior Pathology In Alzheimer's Disease Rating Scale (BEHAVE-AD), a scale for sleep-wake disturbances, and actigraphy to monitor activity rhythm. Behavioral symptoms improved with treatment. No changes in sleep-wake measures were found. There was an advance of the activity rhythm acrophase during treatment. These results suggest that short-time bright light improves behavioral symptoms and aspects of activity rhythm disturbances even in severely demented subjects.

Jones RW, Soininen H, Hager K, Aarsland D, Passmore P, Murthy A, Zhang R, Bahra R. · Research Institute for the Care of the Elderly, St Martin's Hospital, Bath, UK. · Int J Geriatr Psychiatry. · Pubmed #14716700 No free full text.

Abstract: OBJECTIVES: To compare directly, in the same patient cohort, the ease of use and tolerability of donepezil and galantamine in the treatment of Alzheimer's disease (AD), and investigate the effects of both treatments on cognition and activities of daily living (ADL). METHODS: Patients with mild to moderate AD from 14 European centres were randomised to receive open-label donepezil (up to 10 mg once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to the approved product labelling. Physicians and caregivers completed questionnaires rating satisfaction with treatment/ease of use in daily practice. Secondary assessments were the ADAS-cog, the MMSE, and the DAD scale to assess ADL. Tolerability was evaluated by reporting adverse events (AEs). RESULTS: Both physicians and caregivers reported significantly greater overall satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n = 56) at weeks 4, 12, and endpoint (week 12 LOCF; all p-values <0.05). Significantly greater improvements in cognition were also observed for donepezil versus galantamine on the ADAS-cog at Week 12 and endpoint (p-values <0.05). ADL improved significantly in the donepezil group compared with the galantamine group at weeks 4, 12, and endpoint (p-values <0.05). Most AEs were mild to moderate, however, 46% galantamine-treated patients reported gastrointestinal AEs vs 25% donepezil patients. CONCLUSIONS: Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in this direct comparative trial. Both treatments were well tolerated, with more gastrointestinal AEs reported for galantamine vs donepezil.

Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosén E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttilä T, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K. · Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. · JAMA. · Pubmed #19622817 No free full text.

Abstract: CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.

Aarsland D, Brønnick K, Larsen JP, Tysnes OB, Alves G, Anonymous00046. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO 8100, N-4068 Stavanger, Norway. · Neurology. · Pubmed #19020293 No free full text.

Abstract: BACKGROUND: Little is known regarding the cognitive impairment in subjects with early, drug-naïve Parkinson disease (PD). The aim of this study was to explore the proportion with mild cognitive impairment (MCI) and subtypes in an incidence cohort of untreated PD in Southern and Western Norway. METHODS: A total of 196 non-demented, drug-naive patients who were recruited after an extensive search of all new cases of PD in the area and 201 healthy control subjects completed a battery of neuropsychological tests of verbal memory, visuospatial, and attentional-executive functioning. Subjects were classified as MCI if the age- and education-corrected z-score was falling 1.5 standard deviations below the mean for at least one of the cognitive domains. RESULTS: The PD group was more impaired on all neuropsychological tests than controls, but the effect sizes were small. The largest effect size was found for verbal memory. A total of 18.9% of the patients with PD were classified as MCI, with a relative risk of 2.1 (1.2-3.6) in PD compared to the control group. Patients with PD with and without MCI did not differ significantly regarding demographic and motor features. Among PD-MCI patients, nearly two-thirds had a non-amnestic MCI subtype, and one third had an amnestic MCI subtype. CONCLUSIONS: The findings demonstrate a twofold increase in the proportion with cognitive impairment in subjects with early, untreated Parkinson disease (PD) compared to controls. This has implications for diagnosis and management of PD. AD = Alzheimer disease; aMCI-MD = amnestic multiple-domain MCI; aMCI-SD = amnestic single-domain MCI; CVLT-2 = California Verbal Learning Test II; IQCode = Informant Questionnaire on Cognitive decline in the elderly; MADRS = Montgomery and Aasberg Depression Rating Scale; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; naMCI-MD = non-amnestic multiple-domain MCI; naMCI-SD = non-amnestic single-domain MCI; PD = Parkinson disease; RR = relative risks; UPDRS = Unified Parkinson's Disease Rating Scale; VOSP = Visual Object and Space Perception Battery.

Aarsland D, Rongve A, Nore SP, Skogseth R, Skulstad S, Ehrt U, Hoprekstad D, Ballard C. · Department of Old Age Psychiatry, Stavanger University Hospital, Bergen, Norway. · Dement Geriatr Cogn Disord. · Pubmed #18974647 No free full text.

Abstract: OBJECTIVE: To find the proportion of dementia with Lewy bodies (DLB) in a referral cohort of patients with a first-time diagnosis of mild dementia. BACKGROUND: The proportion of DLB among the dementia sufferers is not known and the clinical consensus criteria have low sensitivity. We employed the revised DLB criteria to study the proportion with DLB in a community sample of patients with mild dementia. METHODS: From March 2005 to March 2007, we included 196 patients from referrals to all geriatric medicine, old age psychiatry and neurology outpatient clinics in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. RESULTS: 65% had Alzheimer dementia, 20% DLB (16% probable DLB), 5.6% vascular dementia, 5.6% Parkinson disease with dementia, 2.0% frontotemporal dementia and 1.5% alcoholic dementia. There were no significant differences in the proportion with DLB according to age bands and dementia severity groups. The revised criteria for a clinical diagnosis of DLB increased the proportion of probable DLB by 25% compared to the previous criteria. CONCLUSION: DLB is common in patients with mild dementia, and is the second most common type of dementia. The introduction of new clinical criteria for DLB leads to an increase in the proportion diagnosed with probable DLB.

Skogseth R, Mulugeta E, Jones E, Ballard C, Rongve A, Nore S, Alves G, Aarsland D. · Institute of Clinical Medicine, School of Medicine, University of Bergen, Bergen, Norway. · Dement Geriatr Cogn Disord. · Pubmed #18536520 No free full text.

Abstract: BACKGROUND: The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer's disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer's disease. METHODS: The levels of the 42-amino-acid form of beta-amyloid (A beta(1-42)), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. RESULTS: Our result shows that apathy is significantly correlated with tau and p-tau but not with A beta(1-42). There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid A beta(1-42), tau or p-tau concentrations. CONCLUSION: Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer's disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.

Beyer MK, Larsen JP, Aarsland D. · Department of Radiology, Stavanger University Hospital, Stavanger, Norway. · Neurology. · Pubmed #17709706 No free full text.

Abstract: BACKGROUND: The nosologic relationship between dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) is continuously being debated. We conducted a study using voxel-based morphometry (VBM) to explore the pattern of cortical atrophy in DLB and PDD. METHODS: Seventy-four patients and healthy elderly were imaged (healthy elderly n = 20, PDD n = 15, DLB n = 18, and Alzheimer dementia [AD] n = 21).Three dimensional T1-weighted MRI were acquired, and images analyzed using VBM. The following diagnostic criteria were used: criteria proposed by the third report of the DLB Consortium for DLB, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Diseases Association criteria for AD, and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for dementia in PDD. RESULTS: Overall dementia severity was similar in the dementia groups. We found more pronounced cortical atrophy in DLB than in PDD in the temporal, parietal, and occipital lobes. Patients with AD had reduced gray matter concentrations in the temporal lobes bilaterally, including the amygdala, compared to PDD. Compared to DLB, the AD group had temporal and frontal lobe atrophy. CONCLUSION: We found that despite a similar severity of dementia, patients with dementia with Lewy bodies (DLB) had more cortical atrophy than patients with Parkinson disease with dementia (PDD), indicating different brain substrates underlying dementia in the two syndromes. Together with previous studies reporting subtle clinical and neurobiologic differences between DLB and PDD, our findings support the hypothesis that PDD and DLB are not identical entities, but rather represent two subtypes of a spectrum of Lewy body disease.

Bronnick K, Emre M, Lane R, Tekin S, Aarsland D. · Norwegian Centre for Movement Disorders, Stavanger University Hospital, Helse Stavanger, Norway. · J Neurol Neurosurg Psychiatry. · Pubmed #17287236 No free full text.

Abstract: OBJECTIVE: To compare the profile of cognitive impairment in Alzheimer's disease (AD) with dementia associated with Parkinson's disease (PDD). METHODS: Neuropsychological assessment was performed in 488 patients with PDD and 488 patients with AD using the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Logistic regression analysis was used to investigate whether the diagnosis could be accurately predicted from the cognitive profile. Additionally, the cognitive profiles were compared with a normative group using standardised effect sizes (Cohen's d). RESULTS: Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7%. Poor performance of the AD patients on the orientation test in ADAS-cog best discriminated between the groups, followed by poor performance of the PDD patients on the attentional task in MMSE. Both groups showed memory impairment, AD patients performing worse than PDD patients. CONCLUSION: The cognitive profile in PDD differs significantly from that in AD. Performance on tests of orientation and attention are best in differentiating the groups.

Gotti C, Moretti M, Bohr I, Ziabreva I, Vailati S, Longhi R, Riganti L, Gaimarri A, McKeith IG, Perry RH, Aarsland D, Larsen JP, Sher E, Beattie R, Clementi F, Court JA. · CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Italy. · Neurobiol Dis. · Pubmed #16759874 No free full text.

Abstract: Antibodies raised against human alpha2-6 and beta2-4 nicotinic receptor subunits were utilized to fractionate (3)H-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained alpha4 and beta2 subunits. In normal cortex, 10% of binding was also associated with alpha2 subunits, whereas in the striatum, contributions by alpha6 (17%) and beta3 (23%) were observed. Minimal binding (< or =5%) was associated with alpha3. In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was associated with reductions in alpha4 (50%, P < 0.01) and beta2 (30-38%, P < 0.05). In Parkinson's disease and dementia with Lewy bodies, striatal deficits in alpha6 (91 and 59% respectively, P < 0.01) and beta3 (72 and 75%, P < 0.05) tended to be greater than for alpha4 and beta2 (50-58%, P < 0.05). This study demonstrates distinct combinations of subunits contributing to heteromeric nicotinic receptor binding in the human brain that are area/pathway specific and differentially affected by neurodegeneration.

Janvin CC, Larsen JP, Salmon DP, Galasko D, Hugdahl K, Aarsland D. · Stavanger University Hospital, Section of Geriatric Psychiatry, Stavanger, Norway. · Mov Disord. · Pubmed #16211595 No free full text.

Abstract: We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.

Aarsland D, Perry R, Larsen JP, McKeith IG, O'Brien JT, Perry EK, Burn D, Ballard CG. · Section of Geriatric Psychiatry, Central Hospital, Rogaland, Stavanger, Norway. · J Clin Psychiatry. · Pubmed #15889951 No free full text.

Abstract: BACKGROUND: Severe sensitivity to neuroleptic agents is a major clinical problem in dementia with Lewy bodies (DLB), but has not been determined in Parkinson's disease (PD) and PD with dementia (PDD). METHOD: Severe neuroleptic sensitivity reactions (NSRs) were evaluated according to an operationalized definition blind to clinical and neuropathologic diagnoses in prospectively studied patients exposed to neuroleptics from 2 centers. The study was conducted from June 1995 to May 2003. RESULTS: Ninety-four patients were included (15 with DLB, 36 with PDD, 26 with PD, 17 with Alzheimer's disease, all diagnosed with various operational criteria). Severe NSR only occurred in patients with Lewy body disease: DLB (8 [53%]), PDD (14 [39%]), and PD (7 [27%]), but did not occur in Alzheimer's disease (p = .006). Severe NSR was not associated with other clinical or demographic features. In DLB, severe NSR was not associated with neuropathologic indices (Consortium to Establish a Registry for Alzheimer's Disease staging, Braak staging, or cortical distribution of Lewy bodies). CONCLUSIONS: An operationalized evaluation of severe NSR blind to diagnosis confirmed the high prevalence in DLB and identified high frequencies in Parkinson's disease and PDD with important implications for clinical practice.

Perry E, Ziabreva I, Perry R, Aarsland D, Ballard C. · Newcastle General Hospital, MRC Bldg., Westgate Rd., Newcastle upon Tyne, NE4 6BE, UK. · Neurology. · Pubmed #15642917 No free full text.

Abstract: Choline acetyltransferase in temporal cortex was evaluated as a marker of cholinergic function in autopsied dementia cases (9 vascular dementia [VaD] cases, 12 "mixed" VaD and Alzheimer disease [AD] cases, 10 AD cases, 12 control subjects). Patients with AD (t = 2.5, p = 0.02) and "mixed" VaD and AD (t = 3.8, p = 0.001) had greater cholinergic deficits than age-matched control subjects and patients with "pure" VaD. The absence of cholinergic deficits in "pure" VaD may be relevant to the pharmacologic treatment of these patients.

Aarsland D, Andersen K, Larsen JP, Perry R, Wentzel-Larsen T, Lolk A, Kragh-Sørensen P. · Section of Geriatric Psychiatry, Central Hospital of Rogaland, Stavanger, N-4095 Hillevåg, Norway. · Arch Neurol. · Pubmed #15596611 links to  free full text

Abstract: OBJECTIVES: To measure the rate and predictors of change on the Mini-Mental State Examination in patients with Parkinson disease (PD) and to compare that change with the Mini-Mental State Examination changes of patients with Alzheimer disease and nondemented subjects. PATIENTS: Patients with PD were drawn from a community-based cohort in Rogaland County, Norway. Those who were without cognitive impairment at disease onset and participated in 1 or more assessments after visit 1 were included and examined after 4 years (visit 2) and 8 years (visit 3). Motor, cognitive, and psychiatric symptoms were rated using standardized scales at visit 1. Two population-based cohorts of patients with Alzheimer disease and nondemented control subjects were included for comparison. Data were analyzed using a mixed-effects model. RESULTS: One hundred twenty-nine PD patients (57% women) were included. The mean (SD) Mini-Mental State Examination score at visit 1 was 27.3 (5.7). The mean annual decline in score from visit 1 to visit 3 was 1.1 (95% confidence interval, 0.8 to 1.3; 3.9% change from visit 1). Patients with PD and dementia (n = 49) had an annual decline from visit 1 to visit 2 of 2.3 (95% confidence interval, 2.1 to 2.5; 9.1% change from visit 1), compared with 2.6 (95% confidence interval, 2.3 to 2.8; 10.6% change from visit 1) in the patients with Alzheimer disease (n = 34) (mean annual decline among patients with PD and dementia vs patients with Alzheimer disease, not significant). The change in score for nondemented PD patients (n = 80) was small and similar to that for nondemented control subjects (n = 1621). Old age, hallucinations, and more severe motor symptoms (rigidity and motor scores mediated by nondopaminergic lesions) at visit 1 were significantly associated with a more rapid cognitive decline in patients with PD. CONCLUSIONS: The mean annual decline on the Mini-Mental State Examination for PD patients was 1 point. However, a marked variation was found. In patients with PD and dementia, the mean annual decline was 2.3, which was similar to the decline observed in patients with Alzheimer disease.

O'Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, Aarsland D, McKeith IG. · Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, England. j.t.o' · Arch Neurol. · Pubmed #15210531 links to  free full text

Abstract: BACKGROUND: Dementia with Lewy bodies (DLB) is a common form of late-life dementia that can be difficult to differentiate from other disorders, especially Alzheimer disease (AD), during life. At autopsy the striatal dopaminergic transporter is reduced. OBJECTIVES: To examine the extent and pattern of dopamine transporter loss using iodine I 123-radiolabeled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) with single-photon emission computed tomography (SPECT) in DLBs compared with other dementias and to assess its potential to enhance a differential diagnosis. DESIGN: Cohort study comparing FP-CIT with criterion standard of consensus clinical diagnosis. SETTING: General hospital. PARTICIPANTS: One hundred sixty-four older subjects (33 healthy older control subjects, 34 with NINCDS/ADRDA [National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association]-confirmed AD, 23 with consensus guideline-confirmed DLB, 38 with United Kingdom's Parkinson Disease Society Brain Bank-confirmed Parkinson disease [PD], and 36 with PD and dementia). INTERVENTIONS: Injection of (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane with SPECT scan performed at 4 hours. MAIN OUTCOME MEASURES: Visual ratings of scans and region of interest analysis. RESULTS: Significant reductions (P<.001) in FP-CIT binding occurred in the caudate and anterior and posterior putamens in subjects with DLB compared with subjects with AD and controls. Transporter loss in DLBs was of similar magnitude to that seen in PD, but with a flatter rostrocaudal (caudate-putamen) gradient (P =.001), while the greatest loss in all 3 areas was seen in those who had PD and dementia. Both region of interest analysis and visual ratings provided good separation between DLBs and AD (region of interest: sensitivity, 78%; specificity, 94%; positive predictive value, 90%) but not among subjects with DLB, PD, and PD with dementia. CONCLUSIONS: Dopamine transporter loss can be detected in vivo using FP-CIT SPECT in DLB. Further studies, especially of subjects with DLB without PD, are required to fully establish use in clinical practice.

Cormack F, Aarsland D, Ballard C, Tovée MJ. · Psychology Department, The Henry Wellcome Building For Neuroecology, Framlington Place, Newcastle University, Newcastle Upon Tyne, UK. · Int J Geriatr Psychiatry. · Pubmed #15065231 No free full text.

Abstract: OBJECTIVES: Early and accurate diagnosis of Dementia with Lewy Bodies (DLB) to allow the appropriate clinical treatment is a priority, given reports of severe neuroleptic sensitivity and a preferential response to cholinesterase inhibitors in these patients. There have been suggestions that constructional apraxia is prevalent in DLB, and may provide a sensitive marker of the disease. METHODS: This study examined the pentagon drawings of 100 DLB patients, 50 Alzheimer's disease (AD) patients, 81 Parkinson's disease (PD) patients of whom 36 suffered from dementia (PDD). Performance on this task was correlated with cognitive performance on the MMSE and CAMCOG scales. RESULTS: Patients with DLB were found to draw significantly worse pentagons than those with AD or PD, but not those with PDD. Drawing scores were significantly correlated with MMSE scores for the AD and PDD groups but not those with DLB. More detailed analysis of the neuropsychological correlates of constructional performance for patients with AD and DLB, revealed that those with AD showed a broad cognitive basis to their impairment, in DLB drawing was linked only to perception and praxis. CONCLUSIONS: This study has suggests that DLB subjects show an impairment of pentagon copying that is dissociable from more global cognitive impairments, whereas PD patients are relatively unimpaired on pentagon copying and AD and PDD patients show a linkage of their impairment in copying with more global cognitive deficits.

Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP. · Section of Geriatric Psychiatry, Psychiatric Clinic, Central Hospital of Rogaland, Stavanger, and School of Medicine, University of Bergen, Norway. · J Neurol Neurosurg Psychiatry. · Pubmed #12933921 links to  free full text

Abstract: BACKGROUND: The relation between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unknown. OBJECTIVES: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer's disease). DESIGN: Survey of cognitive features. SETTING: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. PATIENTS: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer's disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. MAIN OUTCOME MEASURES: Dementia rating scale subscores corrected for age. RESULTS: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer's disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). CONCLUSIONS: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer's disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer's disease.

Thommessen B, Aarsland D, Braekhus A, Oksengaard AR, Engedal K, Laake K. · Department of Geriatric Medicine, Ullevaal Hospital, Oslo, Norway. · Int J Geriatr Psychiatry. · Pubmed #11802235 No free full text.

Abstract: OBJECTIVE: To characterize the psychosocial burden on spouses living with the elderly suffering from mild dementia, stroke and Parkinson's disease, and to identify patient characteristics associated with it. Materials and methods Data on patient-spouse couples came from three studies of patients with stroke (36 couples), mild dementia (92 couples) and Parkinson's disease (58 couples). The psychosocial burden was recorded by the 15-item Relatives' Stress Scale (RSS). A factor analysis of this instrument produced a one-factor solution (CFI = 0.98) consisting of eight items with good face validity and acceptable reliability within each diagnostic group (Cronbach's alpha range 0.66-0.69). Covariates of this factor were identified using structural equation modeling (SEM) by regression on patient's age, gender, cognitive function (MMSE), activities of daily living (ADL) and depressive symptoms (MADRS). RESULTS: Disorganization of household routines, difficulties with going away for holidays, restrictions on social life, and the disturbances of sleep were the most frequently reported problems in all three groups. According to the mean sumscore on the RSS, the perceived psychosocial burden was similar across the diagnostic groups. In the final SEM model, a lower cognitive function of the patient was associated with a higher psychosocial burden on the spouses of patients with stroke (beta = -1.3, p = 0.01) and Parkinson's disease (beta = -0.89, p < 0.01), while in the dementia group, only an insignificant trend was demonstrated. In the dementia group, a significantly higher burden was identified on female spouses (beta = -0.56, p = 0.04). A heavier burden of care was also associated with depressive symptoms in the patients with Parkinson's disease. In neither group did the final model disclose any effect of ADL function on the spouse's psychosocial burden. CONCLUSION: Spouses caring for patients with dementia, stroke and Parkinson's disease perceive a similar type and level of psychosocial burden, independent of the disease. The cognitive functioning of the patient is a particularly important factor in this, especially when caring for patients with stroke or Parkinson's disease.

Aarsland D, Cummings JL, Larsen JP. · Section of Geriatric Psychiatry, Rogaland Psychiatric Hospital, PO 1163 Hillevåg, 4095 Stavanger, Norway. · Int J Geriatr Psychiatry. · Pubmed #11241724 No free full text.

Abstract: 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 Copyright 2001 John Wiley & Sons, Ltd.