Journal of Alzheimer's Disease - Volume 42, issue s3

Authors: Korczyn, Amos D.

Article Type: Editorial

DOI: 10.3233/JAD-141830

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S1-S1, 2014

Authors: Rentoumi, Vassiliki | Raoufian, Ladan | Ahmed, Samrah | de Jager, Celeste A. | Garrard, Peter

Article Type: Research Article

Abstract: Mixed vascular and Alzheimer-type dementia and pure Alzheimer's disease are both associated with changes in spoken language. These changes have, however, seldom been subjected to systematic comparison. In the present study, we analyzed language samples obtained during the course of a longitudinal clinical study from patients in whom one or other pathology was verified at post mortem. The aims of the study were twofold: first, to confirm the presence of differences in language produced by members of the two groups using quantitative methods of evaluation; and secondly to ascertain the most informative sources of variation between the groups. We adopted …a computational approach to evaluate digitized transcripts of connected speech along a range of language-related dimensions. We then used machine learning text classification to assign the samples to one of the two pathological groups on the basis of these features. The classifiers' accuracies were tested using simple lexical features, syntactic features, and more complex statistical and information theory characteristics. Maximum accuracy was achieved when word occurrences and frequencies alone were used. Features based on syntactic and lexical complexity yielded lower discrimination scores, but all combinations of features showed significantly better performance than a baseline condition in which every transcript was assigned randomly to one of the two classes. The classification results illustrate the word content specific differences in the spoken language of the two groups. In addition, those with mixed pathology were found to exhibit a marked reduction in lexical variation and complexity compared to their pure AD counterparts. Show more

Keywords: Alzheimer's disease, computational methods, diagnosis, language, machine learning, vascular dementia

DOI: 10.3233/JAD-140555

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S3-S17, 2014

Authors: Versijpt, Jan

Article Type: Review Article

Abstract: Until an effective and especially disease-modifying treatment for Alzheimer's disease (AD) and vascular dementia (VaD) is available, the currently available pharmacological therapeutic arsenal aims at merely improving symptomatology. Health economic data make an important contribution to the planning of healthcare services and the estimation of the cost of drug reimbursement. As such, both for cholinesterase inhibitors and, to a lesser extent, for memantine it can be claimed that the direct cost of the drug itself is eclipsed by the cost savings associated with delaying institutionalization or delaying the time of progression into a more severe disease state. The present manuscript …reviews several factors contributing to the costs of dementia, gives an overview of available studies claiming both the effectiveness and cost-effectiveness of current dementia treatments, and highlights strengths and weaknesses of the aforementioned studies. Show more

Keywords: Alzheimer's disease, cholinesterase inhibitors, economics, memantine, pharmaceutical, vascular dementia

DOI: 10.3233/JAD-132639

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S19-S25, 2014

Authors: Di Donato, Ilaria | Dotti, Maria Teresa | Federico, Antonio

Article Type: Review Article

Abstract: Adult-onset leukoencephalopathies are clinically and pathologically heterogeneous diseases, characterized by overlapping clinical and neuroradiological features and a difficult diagnostic process. Nevertheless, knowledge of the metabolic and genetic basis of leukoencephalopathies is constantly increasing. This article provides an overview of currently known leukoencephalopathies in adulthood, emphasizing, in addition to the classical forms, their atypical clinical presentations. In particular, we review the clinical spectrum and the molecular pathogenesis of certain adult-onset leukoencephalopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebroretinal microangiopathy with calcifications and cysts (CRMCC), hereditary diffuse …leukoencephalopathy with spheroids (HDLS), fragile X-associated tremor/ataxia syndrome (FXTAS), vanishing white matter disease (VWM), autosomal dominant leukodystrophy due to lamin B1 duplication (ADLD), and vascular leukoencephalopathy mapping to chromosome 20q13. Show more

Keywords: Adult onset leukoencephalopathies, inherited diseases, white matter

DOI: 10.3233/JAD-141026

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S27-S35, 2014

Authors: Pavlovic, Aleksandra M. | Pekmezovic, Tatjana | Tomic, Gordana | Trajkovic, Jasna Zidverc | Sternic, Nada

Article Type: Research Article

Abstract: Introduction: Cerebral small vessel disease (SVD) is a common cause of cognitive impairment and vascular dementia. Objective: We aimed to investigate predictors of cognitive decline in patients with SVD who initially presented with first-ever small subcortical stroke of lacunar type but had normal cognitive status. Methods: A total of 294 patients with SVD were evaluated 3–5 years after initial presentation. We analyzed baseline demographic data, vascular risk factors, functional status expressed as score on modified Rankin Scale, total number of lacunar infarcts, and severity of white matter hyperintensities (WMH) on magnetic resonance imaging with Age-Related White …Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. Results: At follow-up, vascular cognitive impairment (VCI) on any type was detected in 188 (63.9%) of SVD patients, with 65 (22.1%) meeting criteria for vascular dementia and 123 (41.8%) presenting with cognitive impairment not dementia. Patients with VCI were older (64.4 ± 10.3 in VCI versus 58.6 ± 10.5 years in non-VCI; p < 0.0001) at the time of initial clinical presentation and more frequently male (57.9% VCI versus 46.2% non-VCI; p = 0.052). No difference was noted in frequency of vascular risk factors in VCI versus non-VCI cases. Multivariate logistic regression analysis adjusted by age and gender identified overall severity of WMH (tARWMC HR 1.42, 95% CI 1.01–2.00; p0.043) and total number of lacunar infarcts (HR 3.06, 95% CI 1.71–5.50, p < 0.001) as independent predictors of cognitive decline. Conclusion: In patients with SVD, independent predictors of VCI were baseline severity of WMH and total number of lacunar infarcts. Show more

Keywords: Lacunar infarct, small vessel disease, stroke, vascular cognitive impairment, white matter hyperintensities

DOI: 10.3233/JAD-132606

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S37-S43, 2014

Authors: Trubnikova, Olga A. | Mamontova, Anastasia S. | Syrova, Irina D. | Maleva, Olga V. | Barbarash, Olga L.

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) may contribute to the development of postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG). Objective: The aim of this study was to investigate the incidence of early and long-term POCD after CABG in coronary heart disease patients with and without preoperative MCI. Methods: The study enrolled two groups of males with coronary heart disease: 51 without MCI (mean age 56.0 ± 6.42 years) and 50 with MCI (mean age 56.4 ± 5.55 years). Baseline clinical characteristics as well as durations of cardiopulmonary bypass and aortic cross-clamping were similar between …the two groups. MCI was defined as a Mini–Mental State Examination score of less than 28. All patients underwent detailed neuropsychological examinations (12 tests) before and 7–10 days and 1 year after surgery. The incidence of early and long-term POCD was estimated on the basis of criteria defined as a 20% decline on 20% of the tests. Results: Early POCD was diagnosed in 72% of cases in patients with MCI and in 79% of those without MCI (p = 0.5; odds ratio [OR] = 0.68; 95% confidence interval [CI] 0.2–2.2). Long-term POCD was diagnosed in 72% of MCI patients and in 70% of non-MCI patients (p = 0.8); OR = 1.08 (95% CI 0.4–2.9). Conclusions: Our results show that the presence of MCI is not the leading cause of either early or long-term POCD in patients undergoing CABG. Further research should focus on the contribution of important clinical factors, including progression of atherosclerosis and adherence, to post-CABG POCD. Show more

Keywords: Cognition disorders, coronary artery bypass grafting, mild cognitive impairment, postoperative complication

DOI: 10.3233/JAD-132540

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S45-S51, 2014

Authors: Graf, Christophe E. | Rossi, Cécile | Giannelli, Sandra V. | Nobari, Bentolhoda Heyrani | Gold, Gabriel | Herrmann, François R. | Zekry, Dina

Article Type: Research Article

Abstract: Background/ Objective: The association between vitamin D levels and cognitive function remains a controversial issue especially in the very old, highly comorbid patients. We address the relative contribution of vitamin D when taking into account potential confounders well known to be involved in cognitive decline. Methods: We investigated, in a prospective study of 428 very old inpatients from the Geneva geriatric hospital (mean age 85.2y ± 6.8; 74.1% women), the association between 25-hydroxyvitamin D (25(OH)D) levels with dementia and mild cognitive impairment (MCI), taking into account comorbid conditions, functionality, malnutrition, ApoE genotype, vitamin B12, calcium, and albumin …as independent variables. Results: 25(OH)D level was not different between the cognitively normal (n = 200), MCI (n = 46), and demented (n = 182) patients nor between the different etiologies of dementia. In polytomous logistic regression, the 25(OH)D level neither as a continuous variable nor as a categorical variable increased the risk to be MCI or demented. The 25(OH)D level did not predict conversion from normal or MCI to dementia in the 315 subjects who completed the 2 years follow-up. No changes were observed in the full adjusted model after taking into account the independent variables. Similarly, considering only the group of cognitively normal subjects, the 25(OH)D level was not associated with impairment of specific cognitive domain. Conclusion: In this cohort of old hospitalized patients with a high burden of comorbidities, the 25(OH)D level alone or adjusted for confounders is not associated with cognitive status and did not predict conversion to dementia. Show more

Keywords: Cognition, conversion, dementia, elderly, 25-hydroxyvitamin D, vitamin D

DOI: 10.3233/JAD-132612

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S53-S61, 2014

Authors: Bruce, David G. | Davis, Wendy A. | Starkstein, Sergio E. | Davis, Timothy M.

Article Type: Research Article

Abstract: Background: The pathway linking type 2 diabetes and cognitive disorders remains poorly understood, and there are many potential risk factors. Objective: To conduct a longitudinal study of risk factors in middle-aged patients with type 2 diabetes. Methods: Type 2 patients from the Fremantle Diabetes Study underwent comprehensive assessment of risk factors in 1993/1996 and cognitive assessment in 2008/2010. After a cognitive screen (Mini-Mental State Examination), the Clinical Dementia Rating was used to define cognitive impairment (rating 0.5) and dementia. The methodology was similar to a previous report in older patients from the same cohort permitting comparison …with that study. Results: Of 335 eligible survivors, aged 57.5 ± 9.2 years at baseline and 72.2 ± 9.1 years at cognitive assessment, 14.7 ± 1.1 years later, 276 were cognitively normal, 27 had cognitive impairment, 17 had dementia, and 15 were unclassifiable. Independent, baseline predictors of dementia were age, poorer education, and cigarette smoking. Predictors of cognitive impairment included insulin therapy and fasting glucose (negative association), while diabetic retinopathy was an additional predictor of cognitive impairment and dementia combined. Conclusion: This study identified diabetes-specific risk factors, insulin therapy and diabetic retinopathy, that may explain the excess risk for cognitive disorders in type 2 diabetes. These risk factors differed from a previous report in older patients and the main difference appears to be related to duration of diabetes in the respective samples. The duration of diabetes or its manifestations is an important determinant of the impact of diabetes on cognitive disorders. Smoking is another important modifiable risk factor. Show more

Keywords: Cardiovascular risk factors, cognitive impairment, dementia, longitudinal study, type 2 diabetes

DOI: 10.3233/JAD-132654

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S63-S70, 2014

Authors: Anastasiou, Costas A. | Yannakoulia, Mary | Scarmeas, Nikolaos

Article Type: Review Article

Abstract: The active form vitamin D is a seco-steroid with multiple neurotrophic and neuroprotective functions in the central nervous system. Robust evidence from studies in animals suggests that vitamin D deficiency may impair brain physiological functioning causing anatomical and behavioral adverse effects. On the other hand, vitamin D has been found to be protective against biological processes associated with Alzheimer's disease and cognition, including amyloid-β deposition, inflammation, calcium homeostasis, and corticosteroid-induced perturbations in cortical areas and the hippocampus. Human studies that examined the relationship between vitamin D status and cognitive function have provided inconclusive results. The majority of cross-sectional and longitudinal …studies suggest a potentially protective association, whereas results from clinical trials are mostly negative, or at best, controversial. We review these studies in humans, with particular emphasis on randomized and observational prospective ones. Show more

Keywords: Alzheimer's disease, amyloid, cholecalciferol, cognition, dementia, vitamin D

DOI: 10.3233/JAD-132636

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S71-S80, 2014

Authors: Vyhnalek, Martin | Nikolai, Tomas | Andel, Ross | Nedelska, Zuzana | Rubínová, Eva | Marková, Hana | Laczó, Jan | Bezdicek, Ondrej | Sheardova, Katerina | Hort, Jakub

Article Type: Research Article

Abstract: Background and Objective: Cognitive deficits in older adults attributable to Alzheimer’s disease (AD) pathology are featured early on by hippocampal impairment. Among tests used to evaluate memory, verbal memory tests with controlled encoding and cued recall are believed to be specific for hippocampal impairment. The objective of this study was to assess the relation between left and right hippocampal volumes and several frequently used memory tests. Methods: Fifty six nondemented older adults (30 with amnestic mild cognitive impairment and 26 cognitively healthy older adults) underwent neuropsychological testing including: 1) The Enhanced Cued Recall test (ECR), a memory test …with controlled encoding and recall; 2) the Auditory Verbal Learning Test (AVLT), a verbal memory test without controlled encoding and with delayed recall; and 3) The Rey-Osterrieth Complex Figure test (ROCF), a visuospatial memory test–recall condition. 1.5T brain MRI scans were used to measure estimated total intracranial volume (eTIV) along with hippocampal right and left volumes, which were measured with quantitative volumetry using FreeSurfer package (version 4.4.0). Spearman partial correlation controlled for age was used to correct for non-normal score distribution and effect of age. Results: We found moderate correlations of hippocampal volumes with AVLT 1–5 scores, AVLT delayed recall, ECR free and total recall, and ROCF reproduction. Total recall in ECR using cued recall was not superior to any of the free recall tests. No correlation in any memory test was achieved with eTIV. Conclusion: Verbal memory tests, either with controlled encoding and cued delayed recall (ECR), or without it (AVLT), as well as nonverbal memory test with delayed recall (ROCF), equally reflect hippocampal atrophy in nondemented older adults. Show more

Keywords: Amnestic mild cognitive impairment, episodic memory, hippocampus, MRI

DOI: 10.3233/JAD-132642

Citation: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S81-S90, 2014