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Mild AD (mild + ad)
Selected AbstractsEffects of Alzheimer's disease and mild cognitive impairment on driving ability: a controlled clinical study by simulated driving testINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2009Cristina 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] Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. L. F. Balthazar Background:, Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. Methods:, We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. Results:, Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. Discussion:, We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD. [source] Prevalence and cognitive impact of cerebrovascular findings in Alzheimer's disease: a retrospective, naturalistic studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009N. 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] Working memory in early Alzheimer's disease: a neuropsychological reviewINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2010J. D. Huntley Abstract Background Reports of the extent of working memory (WM) impairment in early Alzheimer's disease (AD) have been inconsistent. Using the model of WM proposed by Baddeley, neuropsychological evidence for the impairment of WM in early AD is evaluated. Method Literature searches were performed using Medline, PsycINFO and Embase databases. Individual papers were then examined for additional references not revealed by computerised searches. Results Phonological loop function is intact at the preclinical and early stages of AD, becoming more impaired as the disease progresses. In mild AD, there is impairment on tasks assessing visuospatial sketchpad (VSS) function; however, these tasks also require executive processing by the central executive system (CES). There is evidence that the CES is impaired in mild AD and may be affected in the earlier preclinical stage of the disease. Episodic buffer function may be impaired but further research is required. Conclusions Future research into central executive functioning at the earliest stages of the disease, combined with further longitudinal studies, needs to be carried out. Tasks to assess the proposed functions of the episodic buffer and specific tests of the VSS suitable for AD subjects need to be developed and validated. Learning more about these processes and how they are affected in AD is important in understanding and managing the cognitive deficits seen in the early stages of AD. 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 2009Hans 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 testINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2009Cristina 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] 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 2008Fati 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] Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young childrenPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2003Ting Fan Leung Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6,4.2] were recruited. Their SCORAD score was 23.5 (12.5,33.5). Serum concentrations of MDC, TARC, EOX, IP-10 and MCP-1 were 2551 (1978,3935), 1469 (1125,3070), 68 (57,85), 126 (101,226) and 518 (419,614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r =,0.608, p = 0.004) and its extent (r =,0.629, p = 0.003) and intensity (r =,0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r =,0.474, p = 0.035) and intensity (r =,0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children. [source] Executive dysfunction can explain word-list learning disability in very mild Alzheimer's disease: The Tajiri ProjectPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2004RYUSAKU HASHIMOTO msc Abstract, Elderly people with questionable dementia (i.e. a Clinical Dementia Rating (CDR) of 0.5) have been focused on as representing the borderline zone condition between healthy people and dementia patients. Many of them are known to have pathologic traits of very mild Alzheimer's disease (AD). Although they present mild memory disorder, the underlying mechanism has not been fully investigated. Herein is reported the mechanism of learning disability in very mild AD. Eighty-six CDR 0.5 participants and 101 age- and education-matched healthy controls (CDR 0) were randomly selected from a community in the town of Tajiri, Miyagi Prefecture. The word-recall task of the Alzheimer Disease Assessment Scale,Japanese (i.e. learning and recall of 10 words) was administered. The numbers of words recalled in each trial and those never recalled throughout the trials were compared for the two CDR groups. The serial-position function was depicted for three parts (i.e. primary, middle, and recency). The CDR 0.5 group recalled significantly fewer words than the CDR 0 group. The number of never-recalled words was greater in the CDR 0.5 group. A remarkable difference was found in the middle part of the word list. The number of never-recalled words of the CDR 0.5 group was greater in the middle part. The large number of never-recalled words accounted for the poor learning performance of very mild AD participants. The results suggested that very mild AD participants have difficulty in learning and retaining words in the middle part of the word-list because of a functional decline of the central executive system. [source] Relationship between psychiatric symptoms and regional cerebral blood flow in patients with mild Alzheimer's diseasePSYCHOGERIATRICS, Issue 3 2008Keisuke NAKAJIMA Abstract Background:, Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in patients with dementia and often cause serious problems. However, the cause of BPSD has not yet been elucidated. Moreover, the precise evaluation of BPSD in mild dementia has not been studied in any great detail. In the present study, we investigated the relationship between psychiatric symptoms and regional cerebral blood flow (rCBF) in patients with mild Alzheimer's disease (AD). Methods:, The present study included 47 patients (20 men and 27 women) who were diagnosed with mild AD. Mean patient age was 72.8 ± 8.2 years. Single photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer (99mTc-ECD) was performed in all patients. The SPECT data were analyzed using a three-dimensional stereotactic region of interest template, which evaluated CBF in 24 segments. Psychiatric symptoms were evaluated in patients using the Brief Psychiatric Rating Scale. Each psychiatric symptom was designated as ,symptom present' in cases in which the BPRS item score was more than 3. We compared 10 segments of rCBF in symptom-present patients with those in symptom-absent patients. Results:, Motor retardation was the most common psychiatric symptom (36.2%), followed by depression (19.1%), anxiety (17.0%), emotional withdrawal (17.0%), and somatic concern (14.9%). Alzheimer's disease patients with motor retardation exhibited a tendency towards lower rCBF in seven segments (left callosomarginal, bilateral parietal, bilateral angular, and bilateral temporal). However, no specific tendency was observed in depression, anxiety, and somatic concern. Conclusions:, In the present study, we observed a tendency for decreased brain perfusion in patients with motor retardation. Further studies are necessary to confirm that this trend contributes to the appearance of psychiatric symptoms in patients with mild AD. [source] Effect of rosmarinic acid on atopic dermatitisTHE JOURNAL OF DERMATOLOGY, Issue 12 2008Jongsung LEE ABSTRACT Rosmarinic acid is known to have anti-inflammatory and immunomodulatory activities. This study was performed to evaluate the effect of rosmarinic acid on atopic dermatitis (AD), one of the inflammatory disorders of the skin. Twenty-one subjects (14 women and seven men, 5,28 years of age) with mild AD participated in this study. Rosmarinic acid (0.3%) emulsion was topically applied to the elbow flexures of AD patients twice a day (once in the morning and once in the evening). All subjects were evaluated for skin conditions before treatment at the first visit, and then at 4 and 8 weeks after treatment. According to local Severity Scoring of Atopic Dermatitis index results, erythema on antecubital fossa was significantly reduced at 4 and 8 weeks (P < 0.05). Transepidermal water loss of the antecubital fossa was significantly reduced at 8 weeks compared to before treatment (P < 0.05). The results from self-questionnaires on the efficacy of rosmarinic acid indicated that dryness, pruritus and general AD symptoms improved. Our investigation into the AD-mitigating effect of rosmarinic acid through in vivo experiments demonstrated the possible clinical use of rosmarinic acid as a therapeutic agent for AD. [source] Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects,ANNALS OF NEUROLOGY, Issue 4 2009Leslie M. Shaw PhD Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-, 1 to 42 peptide (A,1,42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and A,1,42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF A,1,42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for A,1,42, t-tau, and APO,4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/A,1,42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by A,1,42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009 [source] Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's diseaseANNALS OF NEUROLOGY, Issue 1 2008Nina M. Kemppainen MD Objective The reduced risk for Alzheimer's disease (AD) in high-educated individuals has been proposed to reflect brain cognitive reserve, which would provide more efficient compensatory mechanisms against the underlying pathology, and thus delayed clinical expression. Our aim was to find possible differences in brain amyloid ligand 11C-labeled Pittsburgh Compound B ([11C]PIB) uptake and glucose metabolism in high- and low-educated patients with mild AD. Methods Twelve high-educated and 13 low-educated patients with the same degree of cognitive deterioration were studied with PET using [11C]PIB and 18F-fluorodeoxyglucose as ligands. The between-group differences were analyzed with voxel-based statistical method, and quantitative data were obtained with automated region-of-interest analysis. Results High-educated patients showed increased [11C]PIB uptake in the lateral frontal cortex compared with low-educated patients. Moreover, high-educated patients had significantly lower glucose metabolic rate in the temporoparietal cortical regions compared with low-educated patients. Interpretation Our results suggesting more advanced pathological and functional brain changes in high-educated patients with mild AD are in accordance with the brain cognitive reserve hypothesis and point out the importance of development of reliable markers of underlying AD pathology for early AD diagnostics. Ann Neurol 2007 [source] Declining medical decision-making capacity in mild AD: a two-year longitudinal study,BEHAVIORAL SCIENCES & THE LAW, Issue 4 2006Justin S. Huthwaite Psy.D. This is a report of a two-year longitudinal study comparing healthy older adult subjects (n,=,15) and mild Alzheimer's disease (AD) patients (n,=,20) using an objective performance measure of medical decision-making capacity (MDC). Capacity to consent to medical treatment was measured using the Capacity to Consent to Treatment Instrument (CCTI). The CCTI is a psychometric measure that tests MDC using a series of four core capacity standards: S1 (evidencing/communicating choice), S3 (appreciating consequences), S4 (providing rational reasons), and S5 (understanding treatment situation), and one experimental standard [S2] (making the reasonable treatment choice). For each standard, mild AD patients were assigned one of three capacity outcomes (capable, marginally capable, or incapable) based on cut-off scores derived from control group performance. At baseline, mild AD patients performed equivalently with controls on simple standards of evidencing a choice (S1) and making the reasonable choice ([S2]), but significantly below controls on complex standards of appreciation, reasoning, and understanding (S3, S4, and S5) (p,<,0.02). Control performance was stable over time on all capacity standards. At one-year follow-up, the mild AD group did not show significant decline from baseline on any capacity standard. However, at two-year follow-up the mild AD group showed significant declines from baseline on the three complex standards (S3, S4, and S5) (p,<,0.02), and a trend on one of the simple standards (S1). Over the two-year period, the proportion of marginally capable and incapable outcomes in the AD group increased substantially for four of the five standards (S1, S3, S4, and S5). Performance on [S2] remained stable over time in the AD group. We conclude that mild AD patients have impaired MDC at baseline, and demonstrate significant additional decline on complex consent abilities of appreciation, reasoning, and understanding over a two-year period. AD patients also show emerging impairment on the simple consent ability of evidencing choice at two-year follow-up. Capacity outcome data reflect similar declines over time for these four consent standards. The findings suggest the value of early assessment and regular monitoring at two-year intervals of MDC in patients with mild AD. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||