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AD Patients (ad + patient)

Distribution by Scientific Domains

Medical Sciences	85%
Life Sciences	10%
Chemistry	2%

Distribution within Medical Sciences

Neurology	24%
Dermatology	17%
Allergy & Clinical Immunology	10%
Geriatric Medicine	5%
10 Other Subdomains	20%

Selected Abstracts

Imaging of acetylcholine esterase activity in brainstem nuclei involved in regulation of sleep and wakefulness

EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2007
C. Eggers
Positron emission tomography with 11C- N -methyl-4-piperidyl-acetate (MP4A) was applied in eight healthy volunteers and two patients with mild Alzheimer's disease (AD) to assess acetylcholine esterase (AChE) activity in magnetic resonance imaging-identified brainstem nuclei. Uptake ratios in lateral dorsal tegmental and pedunculopontine nuclei relative to cerebellum yielded reproducible values for the AChE activity in controls and reduced values in AD, more marked in a patient with complaints of disturbed sleep. Cortical AChE activity was related to the extent of cognitive impairment which was more severe in the AD patient without sleep disturbance. This preliminary observational study demonstrates the feasibility to image and assess AChE activity in small nuclei of the brain stem. This approach may be helpful to investigate the interaction of various nuclei in the complex network regulating sleep and wakefulness in representative patient groups with documented sleep disturbance. [source]

Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2007
Bengt Winblad
Abstract Background Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations. Methods A 24-week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double-dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24. Results One thousand and fifty-nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p,,,0.01). Conclusion Caregivers of AD patients preferred the patch to the capsule for drug delivery. Preference for the rivastigmine patch could potentially lead to improved compliance and improved clinical benefits. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Advanced glycation endproducts and pro-inflammatory cytokines in transgenic Tg2576 mice with amyloid plaque pathology

JOURNAL OF NEUROCHEMISTRY, Issue 2 2003
Gerald Münch
Abstract Increased expression and altered processing of the amyloid precursor protein (APP) and generation of ,-amyloid peptides is important in the pathogenesis of amyloid plaques in Alzheimer's disease (AD). Transgenic Tg2576 mice overexpressing the Swedish mutation of human APP exhibit ,-amyloid deposition in the neocortex and limbic areas, accompanied by gliosis and dystrophic neurites. However, murine plaques appear to be less cross-linked and the mice show a lower degree of inflammation and neurodegeneration than AD patients. ,Advanced glycation endproducts (AGEs)', formed by reaction of proteins with reactive sugars or dicarbonyl compounds, are able to cross-link proteins and to activate glial cells, and are thus contributing to plaque stability and plaque-induced inflammation in AD. In this study, we analyze the tissue distribution of AGEs and the pro-inflammatory cytokines IL-1, and TNF-, in 24-month-old Tg2576 mice, and compare the AGE distribution in these mice with a younger age group (13 months old) and a typical Alzheimer's disease patient. Around 70% of the amyloid plaque cores in the 24-month-old mice are devoid of AGEs, which might explain their solubility in physiological buffers. Plaque associated glia, which express IL-1, and TNF-,, contain a significant amount of AGEs, suggesting that plaques, i.e. A, as its major component, can induce intracellular AGE formation and the expression of the cytokines on its own. In the 13-month-old transgenic mice, AGEs staining can neither be detected in plaques nor in glial cells. In contrast, AGEs are present in high amounts in both plaques and glia in the human AD patient. The data obtained in this show interesting differences between the transgenic mouse model and AD patients, which should be considered using the transgenic approach to test therapeutical strategies to eliminate plaques or to attenuate the inflammatory response in AD. [source]

Deterioration of intelligence in methamphetamine-induced psychosis: Comparison with alcohol dependence on WAIS-III

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2010
Shih-Ku Lin md
Aims:, Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration. Methods:, The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 ± 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 ± 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale,Third Edition (WAIS-III). Results:, The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 ± 10.8, 84.3 ± 11.9, 81.9 ± 12.1, 85.5 ± 11.9, 84.7 ± 12.5, 85.4 ± 13.6, and 78.5 ± 12.7 in MIP patients and 90.5 ± 12.0, 95.2 ± 11.3, 86.0 ± 13.7, 95.5 ± 11.0, 87.1 ± 14.5, 96.2 ± 13.1, and 84.5 ± 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was <70 and 13 (38.2%) whose full-scale IQ was <85 and >70, while one AD patient had a full-scale IQ <70 (2.9%) and 10 (22%) had full-scale IQ <85 and >70. Conclusions:, Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients. [source]

,-Amyloid immunization approaches for Alzheimer's disease

DRUG DEVELOPMENT RESEARCH, Issue 2 2002
Bruno P. Imbimbo
Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source]

ORIGINAL INVESTIGATIONS: Different Clinical Features of Aortic Intramural Hematoma Versus Dissection Involving the Descending Thoracic Aorta

ECHOCARDIOGRAPHY, Issue 8 2005
Mariano Falconi M.D.
Objective: The objective of this study is to test the hypothesis that the absence of flow communication in aortic intramural hematoma (IMH) involving the descending aorta may have a different clinical course compared with aortic dissection (AD). Methods: We prospectively evaluated clinical and echocardiographic data in AD (76 patients) and IMH (27 patients) of the descending thoracic aorta. Results: Patients did not differ with regard to age, gender, or clinical presentation. IMH and AD had the same predictors of complications at follow-up: aortic diameter (>5 cm) at diagnosis and persistent back pain. Surgical treatment was more frequently selected in AD (39% vs. 22%, P < 0.01) and AD patients who underwent surgical treatment had higher mortality than those with IMH (36% vs. 17%, P < 0.01). There was no difference in mortality with medical treatment (14% in AD vs. 19% in IMH, P = 0.7). During follow-up, of 23 patients with IMH, 11 (47%) showed complete resolution or regression, 6 (26%) increased the diameter of the descending aorta, and typical AD developed in 3 patients (13%). No changes occurred in 14% of the group. Three-year survival rate did not show significant differences between both groups (82 ± 6% in IMH vs. 75 ± 7% in AD, P = 0.37). Conclusion: IMH of the descending thoracic aorta has a relatively frequent rate of complications at follow-up, including dissection and aneurysm formation. Medical treatment with very frequent imaging and timed elective surgery in cases with complications allows a better patient management. [source]

The 28-amino acid form of an APLP1-derived A,-like peptide is a surrogate marker for A,42 production in the central nervous system

EMBO MOLECULAR MEDICINE, Issue 4 2009
Kanta Yanagida
Abstract Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of amyloid-, (A,42) have been sought because they may aid in the diagnosis of AD and for clarification of disease pathogenesis. Here, we demonstrate that human cerebrospinal fluid (CSF) contains three APLP1-derived A,-like peptides (APL1,) that are generated by ,- and ,-cleavages at a concentration of ,4.5,nM. These novel peptides, APL1,25, APL1,27 and APL1,28, were not deposited in AD brains. Interestingly, most ,-secretase modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate the relative production of A,42 cause a parallel increase in the production of APL1,28 in cultured cells. Moreover, in CSF from patients with pathological mutations in presenilin1 gene, the relative APL1,28 levels are higher than in non-AD controls, while the relative A,42 levels are unchanged or lower. Most strikingly, the relative APL1,28 levels are higher in CSF from sporadic AD patients (regardless of whether they are at mild cognitive impairment or AD stage), than those of non-AD controls. Based on these results, we propose the relative level of APL1,28 in the CSF as a candidate surrogate marker for the relative level of A,42 production in the brain. [source]

BRIEF REPORT: Association between MTHFR 677C-T polymorphism and alcohol dependence according to Lesch and Babor typology

ADDICTION BIOLOGY, Issue 4 2009
Amine Benyamina
ABSTRACT Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management. [source]

Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors

EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010
K. Schultz
Background:, Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods:, CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results:, No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions:, Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias. [source]

CSF biomarker profile and diagnostic value in vascular dementia

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2009
G. P. Paraskevas
Background and purpose:, The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (,T) or hyperphosphorylated at threonin-181(,P-181) form and beta amyloid peptide 1,42 (A,42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. Methods:, The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. Results:, Alzheimer's disease and MD showed increased levels of ,T, ,P and reduced levels of A,42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying ,85% of patients, either in the form of a discriminant function or in the form of the ,T × ,P-181/A,42 formula. Conclusions:, Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice. [source]

Confabulation, but not executive dysfunction discriminate AD from frontotemporal dementia

EUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2004
Z. Nedjam
We examined confabulation and performance on frontal/executive tasks in Alzheimer's disease (AD) patients and patients with a diagnosis of probable frontotemporal dementia (FTD). Twenty-two patients with probable AD, 10 patients with probable FTD and 32 normal control subjects entered the study. Executive functions were assessed with the Modified Card Sorting test; a verbal fluency test; the Cognitive Estimation test; and the Stroop test. Confabulations were assessed with a modified version of the Confabulation Battery. The Confabulation Battery included 10 questions tapping each of the following domains: Episodic Memory (memories of personal past episodes), Semantic Memory (knowledge of famous facts and famous people), and Personal Future (personal plans). The results revealed that both AD patients and FTD patients were clearly and equally impaired on tests of executive functions. Both patients' groups confabulated across the three tasks of the Confabulation Battery, but FTD patients confabulated significantly more than AD patients on Episodic Memory and Personal Future. The results failed to provide any evidence of a correlation between the performance on frontal/executive tasks and the tendency to produce confabulatory reports. According to our results, confabulation, more than a deficit of frontal/executive functions, discriminate between AD and FTD. Therefore, screening for confabulation and, possibly, for other types of memory distortions may constitute a useful additional clinical tool in order to discriminate AD from FTD. [source]

Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patients

EXPERIMENTAL DERMATOLOGY, Issue 3 2008
Yoshiko Mizukawa
Abstract: Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well-recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E-selectin but the epitope generated by fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA,, Fuc-TVII+ ESL+ CLA+ and Fuc-TVII, ESL, CLA+ cells. We therefore asked which subpopulations of skin-homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin-homing T cells with the potent capacity to migrate into the skin by analysing their Fuc-TVII expression and E-selectin binding ability in patients with AD. [source]

Deficient translocation of c-Rel is associated with impaired Th1 cytokine production in T cells from atopic dermatitis patients

EXPERIMENTAL DERMATOLOGY, Issue 1 2005
Karsten Dieckhoff
Abstract:, Decreased production of T helper type 1 (Th1) cytokines, such as interferon-, (IFN-,) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-, and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-,B) transcription factors , p65 or c-Rel , show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-, and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-,. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-,B-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD. [source]

Effect of the lactic acid bacterium Streptococcus thermophilus on stratum corneum ceramide levels and signs and symptoms of atopic dermatitis patients

EXPERIMENTAL DERMATOLOGY, Issue 5 2003
Luisa Di Marzio
Abstract:, A reduced amount of total ceramides could be responsible for functional abnormalities of the skin of atopic dermatitis (AD) patients. The ability of an experimental cream containing sonicated Streptococcus thermophilus to increase skin ceramide levels in healthy subjects has been previously reported. The aim of the present work was to investigate the effects of the topical administration of a S. thermophilus -containing cream on ceramide levels of stratum corneum from AD patients. A 2-week application of the cream, containing a sonicated preparation of the lactic acid bacterium S. thermophilus, in the forearm skin of 11 patients led to a significant and relevant increase of skin ceramide amounts, which could have resulted from the sphingomyelin hydrolysis through the bacterial sphingomyelinase. Moreover, in all patients the topical application of our experimental cream also resulted in the improvement of the signs and symptoms characteristic of AD skin (i.e. erythema, scaling, pruritus). [source]

Sensorimotor network rewiring in mild cognitive impairment and Alzheimer's disease

HUMAN BRAIN MAPPING, Issue 4 2010
Federica Agosta
Abstract This study aimed at elucidating whether (a) brain areas associated with motor function show a change in functional magnetic resonance imaging (fMRI) signal in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), (b) such change is linear over the course of the disease, and (c) fMRI changes in aMCI and AD are driven by hippocampal atrophy, or, conversely, reflect a nonspecific neuronal network rewiring generically associated to brain tissue damage. FMRI during the performance of a simple motor task with the dominant right-hand, and structural MRI (i.e., dual-echo, 3D T1-weighted, and diffusion tensor [DT] MRI sequences) were acquired from 10 AD patients, 15 aMCI patients, and 11 healthy controls. During the simple-motor task, aMCI patients had decreased recruitment of the left (L) inferior frontal gyrus compared to controls, while they showed increased recruitment of L postcentral gyrus and head of L caudate nucleus, and decreased activation of the cingulum compared with AD patients. Effective connectivity was altered between primary sensorimotor cortices (SMC) in aMCI patients vs. controls, and between L SMC, head of L caudate nucleus, and cingulum in AD vs. aMCI patients. Altered fMRI activations and connections were correlated with the hippocampal atrophy in aMCI and with the overall GM microstructural damage in AD. Motor-associated functional cortical changes in aMCI and AD mirror fMRI changes of the cognitive network, suggesting the occurrence of a widespread brain rewiring with increasing structural damage rather than a specific response of cognitive network. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source]

The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patients

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2007
Emanuela Tumini
Abstract Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n,=,321) and non-demented control (n,=,208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Impact of cerebrovascular pathology on behavioural and neuropsychiatric symptoms in patients with Alzheimer's dementia: findings from a retrospective, naturalistic study

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2009
A. Klugman
Summary Aim:, Cerebrovascular disease (CVD) has been associated with depression and a host of neuropsychiatric conditions including dementia. This study assessed the relationship between cerebrovascular findings reported on MRI brain scans and neuropsychiatric symptoms (NPS) and behavioural problems in patients with Alzheimer's disease (AD). Methods:, Medical notes were retrospectively reviewed in patients undergoing brain MRI following referral for cognitive impairment to a memory clinic between January 2004 and June 2008. Patients with AD were graded into four categories of CVD severity based on neuroradiology reports and assessed for behavioural and NPS and activities of daily living using Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS) and Bristol Activities of Daily Living (BADL). Frontal lobe symptoms and parkinsonian features were also evaluated. Results:, Of the initial 232 patients who underwent MRI 72% were diagnosed with AD. 89% of AD patients had CVD findings reported on MRI. Moderate-to-severe CVD was present in 47% of patients. None of the AD patients satisfied a diagnosis of vascular dementia. There was no significant relationship observed between level of MRI CVD findings and scores on NPI (p = 0.57), GDS (p = 0.26) and BADL (p = 0.46). The level of CVD severity did not appear to influence frontal lobe and parkinsonian assessments (p = 0.60). Conclusion:, The contribution of CVD to the pathogenesis of various NPS is still debated. Our study, based on patients diagnosed with AD in a memory clinic setting, suggests that there is no relationship between the extent of CVD pathology and neuropsychiatric and behavioural measures in AD patients. Further prospective quantitative studies are needed to assess the role of CVD, if any, in neuropsychiatric and behavioural symptoms in AD. It is possible that the relatively small pathological contribution of CVD to the development of these symptoms is obscured by the effect of the wider neurodegeneration encountered in AD. [source]

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease: a review

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2009
A. Kurz
Summary Background:, Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia). Objectives:, To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results:, The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%). Conclusion:, The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment. [source]

Prevalence and cognitive impact of cerebrovascular findings in Alzheimer's disease: a retrospective, naturalistic study

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009
N. Tabet
Summary Aims:, Cerebrovascular disease (CVD) is a major risk factor for cognitive decline associated with progression to Alzheimer's disease (AD) and dementia. The objective of this study was to retrospectively assess the prevalence of CVD and its cognitive impact in patients with AD in everyday clinical practice. Methods:, Medical notes were retrospectively reviewed for all individuals who presented at East Sussex Memory Clinic (2004,2008) for investigation of cognitive impairment and had brain magnetic resonance imaging (MRI) as part of their clinical work-up. Global cognitive status was assessed with Mini-Mental State Examination (MMSE) and Cambridge Cognitive Examination. The extent of cerebrovascular abnormalities was qualitatively evaluated with MRI. Results:, Notes were reviewed for 232 patients (109 males, 123 females), mean age 76 years (range 62,93), who underwent MRI. Of these, 167 (72%) patients were diagnosed with AD. CVD was present in 89% of AD patients and 47% of patients had moderate to severe cerebrovascular abnormalities. The majority of patients (57%) had MMSE scores in the 21,26 range, indicative of mild AD. There was a trend towards worse cognitive status in patients with more severe CVD, which did not reach significance. Hachinski Ischaemic score indicated these patients did not have vascular dementia (VaD) (mean ± standard deviation 1.1 ± 1.3). Conclusion:, These findings, based on qualitative MRI, indicate that cerebrovascular pathology is a very common associated feature in patients with mild to moderate AD, without VaD. Although the study suggests that CVD does not contribute to cognitive decline, and is not associated with the development of VaD, a non-significant trend was observed towards worsening cognitive status with increasing severity of CVD. The finding of this trend suggests a need for additional research, especially a prospective quantitative method of assessing CVD, to improve our understanding of how CVD contributes to cognitive impairment in AD. [source]

Current epidemiology of atopic dermatitis in south-eastern Nigeria

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2004
Edith N. Nnoruka MB
Background, Atopic dermatitis (AD) is a common pruritic, eczematous skin disorder that runs a chronic and relapsing course. In Nigeria, it is currently on the increase, particularly amongst infants, and has created cost burdens for families. It occurs in association with a personal or family history of asthma, allergic rhinitis and conjunctivitis. Major and minor criteria exist as guidelines for arriving at a diagnosis of AD, and surveys from Western countries have shown that these features, in particular the minor features, vary with ethnicity and genetic background and can be used to aid diagnosis. African dermatologists have also voiced concern that the much used Hanifin criteria for diagnosis of AD may need some adaptation for use in Africa. Objective, To document the features and disease outcomes of AD seen amongst dermatology hospital patients in Enugu, south-eastern Nigeria, with a view to reflecting current features amongst Nigerian Blacks. Methods, A prospective study of AD patients seen over a 2-year period at a tertiary referral dermatology clinic (University of Nigeria Teaching Hospital, Enugu, Nigeria) was carried out. A total of 1019 patients aged between 4 weeks and 57 years were included in the study. Results, The prevalence of AD was 8.5%, which is much higher than the prevalence of AD reported in various parts of Nigeria 15 years ago. AD occurred before the age of 10 years in 523 (51.3%) patients, whilst 250 (24.5%) had onset after 21 years. The earliest age of onset in infants was in the first 6 weeks of life, and this was found in 129 patients (12.7%). Education and occupation of household heads were the most significant (P < 0.001) factors associated with seeking proper health care for the child's AD. Four hundred and forty-one (43.3%) patients presented with subacute atopic eczema and 326 (32%) patients with severe impeteginized eczema. Four hundred and twenty-five patients (41.7%) had at least one first-degree family member with AD (16.7%), allergic rhinitis (10.3%), asthma (14.6%) and allergic conjunctivitis (2.1%), while 55 (13.3%) of controls had a positive family history (P < 0.01) of allergy. A personal history of AD only, without concomitant respiratory allergies, was seen in 486 (47.7%) patients. The face was affected in 431 (42.3%) patients. Inverse distribution of a flexural rash was observed over the extensor aspect of the joints: the elbow in 502 patients (49.3%), the wrist joint in 183 patients (17.9%) and the knee joints in 354 patients (34.7). The commonly observed minor features included xerosis in 719 patients (71%), papular lichenoid lesions in 547 patients (54.1%), infraorbital folds in 498 patients (49.2%), palmar hyper linearity in 524 patients (51.8%) and raised peripheral blood eosinophils in 519 patients (51%), particularly for those with severe AD. Fissured heels, forehead lichenification, orbital darkening, nail pitting, sand paper-like skin lesions on the elbows/knees/lateral malleolli, knuckle dermatitis of the hands, palmar erythema and pitted keratolysis occurred more uncommonly as minor features. Infective complications were very common and included bacterial infections (folliculitis, impetiginized dermatitis and pyodermas) in 425 (41.7%) patients, fungal infections in 377 (37%) patients, parasitic infections (scabies) in 90 (8.8%) patients and viral infection (herpes simplex and molluscum contagiosum) in 29 (2.9%) patients. Thirteen of these atopics were also HIV positive. Aggravating factors most commonly reported included heat intolerance, excessive sweating, humidity, grass intolerance, thick woollen clothing and drug reactions. Only three patients had food intolerance. Three hundred and ten patients (30.4%) recalled their AD being worse in the hot humid periods and 383 (37.6%) could not recall any periods of relief or remission. Conclusions, The prevalence of AD amongst south-eastern Nigerian Blacks is on the increase, as in other areas, although it is still lower here than in other parts of the world. Many conventional minor features were found, but some occurred less frequently than in other countries, which may be attributed to ethnicity. Further studies will be required to confirm the ethnic differences in these features of AD amongst Nigerians and other Africans, to clarify the features of AD that are peculiar to Africans. [source]

Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2009
Antonia L. Pritchard
Abstract Objective Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. Methods Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. Results Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. Conclusion Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment?

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2009
Hans Debruyne
Abstract Objective To determine the reliability of the 30-item Geriatric Depression Scale (GDS-30) for the screening of depressive symptoms in dementia and mild cognitive impairment (MCI) using the Cornell Scale for Depression in Dementia (CSDD) as the ,gold standard'. Methods Diagnosed according to strictly applied clinical diagnostic criteria, patients with MCI (n,=,156) and probable Alzheimer's disease (AD) (n,=,247) were included. GDS-30, CSDD, Mini Mental State Examination (MMSE) and Global Deterioration Scale were assessed in all patients at inclusion. The AD group was divided in three subgroups: mild AD (MMSE,18) (n,=,117), moderate AD (MMSE<,18 and ,10) (n,=,89) and severe AD (MMSE<10) (n,=,38). Results In MCI patients, moderate but highly significant correlations were found between GDS-30 and CSDD scores (Pearson: r,=,0.565; p,<,0.001). In mildly (r,=,0.294; p,=,0.001), moderately (r,=,0.273; p,=,0.010) and severely (r,=,0.348; p,=,0.032) affected AD patients, only weak correlations between GDS-30 and CSDD scores were calculated. ROC curve analysis showed that sensitivity and specificity values of respectively 95% and 67% were achieved when a GDS-30 cut-off score of 8 was applied in MCI patients. In AD patients, too low sensitivity and specificity values did not allow selecting an optimal cut-off score by means of ROC curve analysis. Conclusion Using the CSDD as ,gold standard', we demonstrated that the GDS-30 is a reliable screening tool for depressive symptoms in MCI but not in AD patients. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Effects of Alzheimer's disease and mild cognitive impairment on driving ability: a controlled clinical study by simulated driving test

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2009
Cristina Frittelli
Abstract Objective To assess the effects of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) on simulated car driving ability. Methods Twenty patients with a probable AD of mild severity (Clinical Dementia Rating, CDR,=,1) were compared with 20 subjects with MCI (CD,=,0.5), and a group of age-matched neurologically normal controls on a driving simulation task. Measures of driving competence included the length of run, the number of infractions (omission of stop at pedestrian crossings, speed limits violation), the number of stops at traffic lights, the mean time to collision, and the number of off-road events. Results in the driving competence measures were correlated with scores obtained from simple visual reaction times and mini-mental state examination (MMSE). Results The patients with mild AD performed significantly worse than MCI subjects and controls on three simulated driving measures, length of run and mean time to collision (p,<,0.001), and number of off-road events (p,<,0.01). MCI subjects had only a significantly shorter time-to-collision than healthy controls (p,<,0.001). Simple visual reaction times were significantly longer (p,<,0.001) in patients with AD, compared to MCI and healthy controls, and showed a borderline significant relation (p,=,0.05) with simulated driving scores. Driving performance in the three groups did not significantly correlate with MMSE score as measure of overall cognitive function. Conclusions Mild AD significantly impaired simulated driving fitness, while MCI limitedly affected driving performance. Unsafe driving behaviour in AD patients was not predicted by MMSE scores. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Clustering and switching in semantic fluency: predictors of the development of Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2008
Ana B. Fagundo
Abstract Objective The aims of the study are twofold: (1) to compare semantic fluency, clustering and switching performance among subjects with memory complaints, patients with Alzheimer Disease (AD), and healthy controls; and (2) to examine the clinical utility of the clustering/switching scoring system in the prediction of incident AD in subjects with memory complaints. Methods A semantic fluency task was used to compare thirty eight subjects with memory complaints, forty two AD patients and twenty five healthy controls on the total number of words generated, clustering and switching performance. Subjects with memory complaints were followed-up for a maximum period of two years and re-evaluated. They remained in the memory complaints group (twenty eight subjects) or were defined as probable AD (ten subjects). Results AD patients generated fewer correct words (p,<,0.001) and showed a reduction in clustering (p,=,0.008) and switching (p,<,0.001). Subjects with memory complaints showed a significant reduction in correct words (p,<,0.001) and clustering performance (p,=,0.008) compare to controls. In the first evaluation, the subgroup of patients who converted to AD at follow up produced less correct words (p,<,0.01) and smaller clusters (p,=,0.007) than the subgroup who did not become demented. There were no differences in switching between these two subgroups. AD development was better predicted by cluster size than by the total number of words generated or by switching. Conclusions Subjects with memory complaints and AD patients have an alteration in both qualitative and quantitative aspects of semantic fluency. A clustering analysis could enhance the reliability of early AD diagnosis. Copyright © 2008 John Wiley & Sons, Ltd. [source]

A 2-year follow-up of 233 very mild (CDR 0.5) Alzheimer's disease patients (REAL. FR cohort)

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2008
Fati Nourhashémi
Abstract Objectives Making an early diagnosis of Alzheimer's Disease (AD) is becoming increasingly important. The Clinical Dementia Rating scale (CDR), a semi-structured interview with patient and caregiver, is a global rating scale designed for use in staging dementia. The primary objective of our study was to examine the evolution of AD in individuals with very mild AD (CDR 0.5) across a 2-year follow up. Methods A cohort of AD patients (n,=,682) living in the community were followed during 2 years in 16 centres of the French AD network. Each subject underwent extensive medical examination including the MMSE and CDR every 6 months. Results Two hundred and thirty-three AD patients were rated CDR 0.5 at baseline (mean MMSE score: 23.15,±,2.57). They were younger and reported an average duration of symptoms of approximately 0.8 years less than patients with CDR,,,1. During the 2-year follow-up, none of the AD CDR 0.5 subjects improved; 65% of them showed an increase in the CDR score. The rate of cognitive decline was similar between the AD CDR 0.5 and CDR,,,1 groups. The ADL decline was more significant in patients with CDR,,,1 at inclusion. Conclusions It is certainly possible to identify AD at a very early stage focusing on intra individual change in cognitive and functional impairment. Criteria with a high sensitivity and specificity for detecting AD at an early stage will help to further develop effective pharmacological and behavioural interventions for delaying the onset and progression of the disease. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Reliability and validity of the Japanese version of the Dysexecutive Questionnaire (DEX) in Alzheimer's disease: validation of a behavioral rating scale to assess dysexecutive symptoms in Japanese patients with Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2007
Yoshihiro Shinagawa
Abstract Background Both executive cognitive dysfunction and behavioral problems contribute to dysexecutive symptoms in daily life. The aim of the present study was to develop a behavior rating scale for assessing dysexecutive symptoms in Japanese patients with AD. Method The Dysexecutive Questionnaire (DEX), devised by Burgess et al. (1998), was used to evaluate 122 Japanese patients with AD. The factor structure, internal consistency, test-retest reliability, and construct validity of the Japanese version of the DEX were then examined. Results The Japanese version of the DEX demonstrated a good internal reliability and a good test,retest reliability. Factor analysis revealed three factors that were named ,apathy', ,hyperactivity' and ,planning and monitoring process of the purposive action'. The ,apathy' factor of the DEX was significantly correlated with the ,apathy' score of the Neuropsychiatric Inventory (NPI), while ,planning and monitoring process' factor of the DEX was significantly correlated with the total score of the Frontal Assessment Battery (FAB) and the ,hyperactivity' factor of the DEX was significantly correlated with the ,aggression', ,euphoria' and ,disinhibition' scores of the NPI. Conclusions The Japanese DEX is a reliable and valid instrument for assessing executive dysfunction conveniently in real life situations of AD patients. While two factors, ,apathy' and ,hyperactivity', were associated with emotional and behavioral changes, the ,planning and monitoring process' was associated with the cognitive executive function in the patients with AD. These findings suggest that both a neuropsychiatric syndrome and cognitive function contribute to the dysexecutive symptoms experienced by AD patients in daily life. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Differences in depression symptoms in patients with Alzheimer's and Parkinson's diseases: evidence from the 15-item Geriatric Depression Scale (GDS-15)

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2007
Daniel Weintraub
Abstract Objective Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations. Method The 15-item Geriatric Depression Scale (GDS-15) was administered as a depression screening instrument to 232,AD patients and 266,PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease-specific associations with individual GDS-15 items, and factor analysis was used to assess GDS-15 factor structure in the two populations. Results Controlling for total GDS-15 score and other covariates, AD patients reported more dissatisfaction with life (p,=,0.03) and memory problems (p,<,0.001), while PD patients reported more fearfulness (p,=,0.01), helplessness (p,<,0.01), a preference to stay at home (p,=,0.02), and diminished energy (p,<,0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts. Conclusions The factor structure of the GDS-15 is similar in AD and PD patients with at most mild stage dementia, but between-group differences on 6 of the GDS-15 items suggests the non-specificity of certain items in the two populations. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease

The diagnostic value of tau protein, ,-amyloid (1,42) and their ratio for the discrimination of alcohol-related cognitive disorders from Alzheimer's disease in the early stages

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2005
Elisabeth Kapaki
Abstract Background Chronic and heavy alcohol abuse or dependence may result in impaired cognition and dementia. The increased risk of Alzheimer's disease (AD) in older individuals interferes with the differential diagnosis, especially when dealing with elderly patients with a long history of alcohol abuse. The aim of the present study was to evaluate the diagnostic value of the putative cerebrospinal fluid (CSF) biomarkers tau, ,-amyloid 1,42 (A,42) and their ratio in differentiating alcohol related cognitive disorder (ARCD) from AD. Methods Double-sandwich ELISA (Innotest htau antigen and ,-Amyloid (1,42), Innogenetics) were used to quantify the above markers in a total of 20 patients with ARCD, 33 AD patients with mild to moderate dementia and 50 mentally intact subjects. Results Tau protein successfully differentiated AD from normal ageing with 96% specificity and 93.9% sensitivity and from ARCD with 95% specificity, and 87.9% sensitivity. A,42 alone had a specificity of 88% and a sensitivity of 69.7% in differentiating AD from normal ageing, while the corresponding values for differentiating AD from ARCD were 80% and 84.8% respectively. The tau/A,42 ratio was better than tau alone for differentiating AD from normal ageing (specificity 94%, sensitivity 97%) and better than any of the candidate markers alone, for differentiating AD from ARCD (specificity 100%, sensitivity 97%). Conclusions The combined use of CSF tau and A,42 may be a useful tool in the differential diagnosis of ARCD from AD, especially in the early stages, where diagnostic uncertainty is greater. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Cost of Alzheimer's disease in a developing country setting

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005
M. Zencir
Abstract Purpose To evaluate the economic impact of AD in Denizli, Turkey. Design and Methods This observational study was conducted with 42 AD patients and their primary caregivers. During the initial interview, demographic data and medical histories were collected with questionnaires. For an observational period of 15 days, data on time spent for patient care were collected using standard forms. Calculations on direct cost (e.g. per day medication, outpatient physician visits during the last 3 months), indirect cost (e.g. time spent for care by caregiver for daily living (ADL) and instrumental activity of daily living (IADL)) were made by summing up and taking averages of the appropriate items. ANOVA, and linear regressions were the methods for comparisons. Results The primary caregivers of the patients mainly were their children and/or spouses. The maximum mean time spent (h/week) was 21.0 (17.5) for severely damaged cognition. The average annual cost per case was between $1,766 [95% Confidence Intervals (CI); 1.300,2.231] and $4,930 (95% CI; 3.3714,6.147). The amount of caregiver cost was the most significant item in the overall cost and it showed an increase with the declining cognitive function of patients. Daily medication cost reflected the same pattern. In contrast, cost of outpatient physician was the lowest among the patients with the worst cognition. Conclusions These results suggest that recently AD has become a significant cost for developing countries. This pilot study gives an idea of the cost of AD in developing countries where determining the actual cost can be difficult. Copyright © 2005 John Wiley & Sons, Ltd. [source]