Diagnosis Of Probable Alzheimer's Disease Research Articles

What is the impact of regulatory guidance and expiry of drug patents on dementia drug prescriptions in England? A trend analysis in the Clinical Practice Research Datalink

BackgroundDrugs for dementia have been available in England since 1997. Since their launch, there have been several changes to national guidelines and initiatives that may have influenced prescribing. These include changes in National Institute for Health and Care Excellence (NICE) guidance, several government dementia strategies, the addition of dementia to the Quality and Outcomes Framework (QOF), and the expiry of drug patents. Despite this, there has been little research into the effect of these events on prescribing. This paper examines prescribing trends in England using data from the U.K. Clinical Practice Research Datalink since the launch of drugs for dementia up to 1st January 2016.MethodsWe considered the monthly proportion of patients eligible for treatment, with a diagnosis of probable Alzheimer’s disease, receiving their first prescription for each drug class—namely, acetylcholinesterase (AChE) inhibitors (donepezil, rivastigmine, galantamine) and N-methyl-d-aspartate (NMDA) receptor antagonists (memantine). Trend analysis using joinpoint models was then applied to identify up to two trend changes per treatment of interest.ResultsThe overall trend was for increasing prescriptions in each drug class over the period in which they were studied. This was indicated by the average monthly percentage change, which was 6.0% (95% CI, − 6.4 to 19.9; June 1997 to December 2015) for AChE inhibitors and 15.4% (95% CI, − 77.1 to 480.9; January 2003 to December 2015) for NMDA receptor antagonists. Prescriptions of AChE inhibitors increased at the end of 2012, probably in response to the patent expiry of these drugs earlier that year. The Prime Minister’s Dementia Challenge launched in May 2012 may also have contributed to the observed increase. However, neither this strategy nor patent expiry appeared to influence prescriptions of NMDA receptor antagonists. Instead trend changes in this drug class were driven by NICE guidance released in 2011 that allowed access to these drugs outside of clinical trials.ConclusionsDementia drug prescribing does not always respond to factors such as regulatory guidance, recommendations, or patent expiry, and when it does, not necessarily in a predictable way. This suggests that communication with clinicians may need to be improved to use drugs for dementia more cost-effectively.

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

Alzheimer’s disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VITA) study, a longitudinal, population-based birth cohort study, at baseline and after 90 months or at diagnosis of probable AD. We determined the levels of specific choline phospholipids, some of which have been suggested as potential biomarkers for the prediction of AD. Our results show that during normal aging the levels of lysophosphatidylcholine, choline plasmalogen, and lyso-platelet activating factor increase significantly. Notably, we observed similar but more pronounced changes in the group that developed probable AD. Thus, our results imply that, in terms of choline-containing plasma phospholipids, the conversion to AD mimics an accelerated aging process. We conclude that age, even in the comparatively short time frame between 75 and 82.5 years, is a crucial factor in the quest for plasma lipid biomarkers for AD that must be carefully considered in future studies and trials.

Correlation of Alzheimer’s Dementia Markers

Introduction: Alzheimer’s disease remains a major cause of morbidity, mortality and dependency in older patients with dementia. With increasing age in older population and dementia in western hemisphere, an inexpensive and unified modality for early diagnosis of AD is of utmost importance. Methods: We sought to investigate single photon emission computed tomography (SPECT) imaging of the brain as a less expensive modality in a prospective single blinded study in a cohort with diagnosis of probable Alzheimer’s dementia. Patients’ demographics, family history, Mini Mental Status Exam, brain imaging, biomarkers such as Tau, Amyloid beta protein, and Apo E genotype were obtained and analyzed. We tested different possible correlations models for association of current diagnosis of Alzheimer’s disease with SPECT and biomarkers using Chi-square test. Results: Biochemical markers (Amyloid beta 42 and tau protein) have higher sensitivity in identifying patients with AD. APOE genotype is less sensitive as a diagnostic test. SPECT did not correlate with biomarkers in early AD, but showed higher correlation in moderate and severe dementia. Further investigation is warranted to identify a more sensitive and specific yet inexpensive testing for early diagnosis of AD. Discussion: Biochemical and genetic markers have a closer association with each other and with Alzheimer’s compared to their association with brain imaging of patients with Alzheimer’s disease.

Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease.

Background:Effectiveness of Alzheimer’s disease (AD) treatments may depend critically on the timeliness of intervention.Objective:To compare characteristics and outcomes of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline.Methods:Patients with ≥1 prAD diagnosis and ≥1 follow-up visit were selected from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS; 9/2005-6/2015) and stratified based on the time between the perceived onset of cognitive decline at baseline and first prAD diagnosis (i.e., earlier versus later diagnosis). Characteristics at baseline and prAD diagnosis, clinically meaningful progression, and medication use following prAD diagnosis were compared.Results:Median time from perceived onset of cognitive decline to prAD diagnosis was 4.5 years (earlier diagnosis: ≤3.46; later diagnosis: >5.71). Earlier-diagnosed patients (n = 1,476) were younger at baseline (74.3 versus 76.3 years) and had better cognitive and functional scores than later-diagnosed patients (n = 1,474). At first prAD diagnosis, earlier-diagnosed patients had lower mean global Clinical Dementia Rating (CDR) score (0.8 versus 1.1), higher mean Mini-Mental State Examination (MMSE) (22.6 versus 20.0), and lower mean Functional Activities Questionnaire (11.6 versus 17.3). Earlier- and later-diagnosed patients experienced similar time to a decrease of ≥3 points in MMSE (median 23.2 versus 23.1 months, p = 0.83), but earlier-diagnosed patients had longer time to a CDR score of ≥2 points, and longer times to initiation of AD medication and antipsychotic agents (all p < 0.01).Conclusion:Earlier prAD diagnosis in NACC data is associated with higher cognitive function and lower functional impairment at diagnosis.

Cortical Metabolic and Cognitive Correlates of Disorientation in Alzheimer's Disease.

Orientation to time, date, and place is commonly utilized in clinical settings to aid in diagnosis, staging, and monitoring of Alzheimer's disease (AD). This study aimed to identify the cerebral metabolic correlates of orientation in patients with AD, and the degree to which regions associated with orientation overlap with memory-related structures. Eighty-five patients with a diagnosis of probable AD underwent fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological testing. Orientation items from the Dementia Rating Scale and recognition performance from the Consortium to Establish a Registry for AD (CERAD) Word List Learning test were correlated with cerebral glucose metabolism. Post-hoc analyses examined neuropsychological predictors of orientation. Better orientation performance related to greater cerebral metabolism in the bilateral middle-inferior temporal lobes, bilateral middle-posterior cingulate, left angular gyrus, and left middle occipital gyrus. In comparison, higher CERAD recognition discriminability score was associated with greater metabolic activity in left medial temporal lobe regions including the hippocampal and parahippocampal gyri, and the left fusiform gyrus. Post-hoc behavioral analyses revealed multiple cognitive functions to be related to orientation, including list learning, recognition memory, visuospatial functioning, attention, and language. Findings from the present study suggest that disorientation in AD results from dysfunction of a network of structures and cognitive abilities commonly found to be implicated in AD. The study supports the notion that memory is necessary but not sufficient for successful orientation.

Language and communication non-pharmacological interventions in patients with Alzheimer's disease: a systematic review. Communication intervention in Alzheimer.

ABSTRACTAlzheimer's disease considerably compromises communication skills. Language changes become more prominent as the disease progresses. Deterioration of language and cognition reduces the ability of holding conversations, which has a negative impact on social interaction.OBJECTIVE:To conduct a systematic review of the literature for articles reporting interventions focused on the language and communication of people with Alzheimer's disease (AD) without use of medication.METHODS:We performed a search using the keywords Alzheimer's disease, language, communication, cognition, cognitive intervention, rehabilitation and therapy, and their corresponding Portuguese and Spanish terms, on the SciELO, LILACS, PubMed and PsychINFO databases. We analyzed intervention studies published from 1993 to 2016 that involved stimulation of language skills and/or communication with pre-and post-intervention quantitative results, and whose samples included at least 50% with a diagnosis of probable AD. Studies were analyzed and classified into four levels of evidence, according to the criteria described in the literature.RESULTS:Twenty-eight articles were included. The majority of the designs had medium-to-low scientific evidence. Most interventions showed benefits for at least one language or communicative skill. Eight types of interventions emerged from the analysis of the studies. Further research with higher levels of evidence is recommended in the investigation of interventions focused on language and communication skills of patients with dementia.CONCLUSION:Studies with high levels of evidence on the topic investigated are only being conducted on a small scale. Two intervention techniques seem potentially effective: lexical-semantic approaches and interventions that work with different cognitive skills (including language).

Towards automated dementia diagnosis based upon speech

The clinical diagnosis of Alzheimer’s disease and other dementias is very challenging, especially in the early stages. Our hypothesis is that any disease that effects particular brain regions involved in speech production and processing will also leave detectable finger prints in the speech. The goal of this work is an easy-to-use, non-invasive, inexpensive diagnostic test for dementia that can easily be applied in a clinician’s office or even at home. Experimental evidence suggests that strong discrimination between subjects with a diagnosis of probable Alzheimer’s versus matched normal controls can be achieved with a combination of acoustic features from speech, linguistic features extracted from a transcription of the speech, and results of a mini mental state exam. Progress is reported toward a fully automatic speech recognition system tuned for the speech-to-text aspect of this application. In addition to using state-of-the- art automatic speech recognition techniques such as Deep Learning, recurrent neural networks are used to predict the punctuation in transcribed speech, which is later used for extracting linguistic features. This fully automated system for 73 speakers is combined with 140 manually transcribed speech samples and used for experimental testing of a system for automated detection of Alzheimer’s from speech.

Generation and Partial Characterization of Rabbit Monoclonal Antibody to Amyloid-β Peptide 1-37 (Aβ37).

Secreted soluble amyloid-β 1-37 (Aβ37) peptide is one of the prominent Aβ forms next to Aβ40, and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF Aβ37 levels in combination with Aβ38, Aβ40, and Aβ42 to support the diagnosis of patients with probable Alzheimer's disease (AD), and the value of antibody to Aβ37 to facilitate drug discovery studies. However, the availability of reliable and specific monoclonal antibody to Aβ37 is very limited. Our aims were: 1) to generate and partially characterize rabbit monoclonal antibody (RabmAb) to Aβ37, and 2) to determine whether the antibody detects changes in Aβ37 levels produced by a γ-secretase modulator (GSM). Our generated RabmAb to Aβ37 was found to be specific to Aβ37, since it did not react with Aβ36, Aβ38, Aβ39, Aβ40, and Aβ42 in an ELISA or immunoblotting. The epitope of the antibody was contained in the seven C-terminal residues of Aβ37. The antibody was sensitive enough to measure CSF and plasma Aβ37 levels in ELISA. Immunohistological studies showed the presence of Aβ37-positive deposits in the brain of AD, and Down syndrome persons diagnosed with AD. Our studies also showed that the antibody detected Aβ37 increases in CSF and brains of rodents following treatment with a GSM. Thus, our antibody can be widely applied to AD research, and in a panel based approach it may have potential to support the diagnosis of probable AD, and in testing the effect of GSMs to target AD.

PATIENT CHARACTERISTICS AND OUTCOMES ASSOCIATED WITH RECEIVING AN EARLIER VERSUS LATER DIAGNOSIS OF PROBABLE ALZHEIMER’S DISEASE: EVIDENCE FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER DATA

PATIENT CHARACTERISTICS AND OUTCOMES ASSOCIATED WITH RECEIVING AN EARLIER VERSUS LATER DIAGNOSIS OF PROBABLE ALZHEIMER’S DISEASE: EVIDENCE FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER DATA

Prediction of Conversion from Mild Cognitive Impairment to Alzheimer's Disease Using MRI and Structural Network Features.

Optimized magnetic resonance imaging (MRI) features and abnormalities of brain network architectures may allow earlier detection and accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). In this study, we proposed a classification framework to distinguish MCI converters (MCIc) from MCI non-converters (MCInc) by using a combination of FreeSurfer-derived MRI features and nodal features derived from the thickness network. At the feature selection step, we first employed sparse linear regression with stability selection, for the selection of discriminative features in the iterative combinations of MRI and network measures. Subsequently the top K features of available combinations were selected as optimal features for classification. To obtain unbiased results, support vector machine (SVM) classifiers with nested cross validation were used for classification. The combination of 10 features including those from MRI and network measures attained accuracies of 66.04, 76.39, 74.66, and 73.91% for mixed conversion time, 6, 12, and 18 months before diagnosis of probable AD, respectively. Analysis of the diagnostic power of different time periods before diagnosis of probable AD showed that short-term prediction (6 and 12 months) achieved more stable and higher AUC scores compared with long-term prediction (18 months), with K-values from 1 to 30. The present results suggest that meaningful predictors composed of MRI and network measures may offer the possibility for early detection of progression from MCI to AD.

Are premorbid abnormal personality traits associated with behavioural and psychological symptoms in dementia?

The study aims to investigate associations between behavioural and psychological symptoms of dementia (BPSD) and abnormal premorbid personality traits. Data were obtained from 217 patients with a diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms of late-onset dementia were assessed with the Neuropsychiatric Inventory. Premorbid personality traits were assessed using the Standardised Assessment of Personality. Abnormal premorbid personality traits were categorised with Diagnostic and Statistical Manual of Mental Disorders fourth edition and International Statistical Classification of Diseases and Related Health Problems-10 diagnostic criteria for personality disorders. Abnormal premorbid personality traits were associated with increased behavioural and psychological symptoms in dementia. Cluster A (solitary/paranoid) premorbid personality traits were associated with anxiety, depression and hallucinations. Cluster C (anxious/dependent) traits were associated with a syndrome of depression. The presence of Clusters A (solitary/paranoid) and C (anxious/dependent) abnormal premorbid personality traits seems to affect the expression of certain behavioural and psychological symptoms in dementia, depression in particular. Copyright © 2016 John Wiley & Sons, Ltd.

A Cross-Sectional Analysis of Late-Life Cardiovascular Factors and Their Relation to Clinically Defined Neurodegenerative Diseases.

Studies have demonstrated associations between cardiovascular factors and Alzheimer disease (AD) with minimal focus on other neurodegenerative diseases. Utilizing cross-sectional data from 17,532 individuals in the National Alzheimer's Coordinating Center, Uniform Data Set, we compared the presence of cardiovascular factors [body mass index (BMI), atrial fibrillation, hypertension, hyperlipidemia, and diabetes] in individuals carrying a diagnosis of Probable AD (ProbAD), Possible AD, vascular dementia, dementia with Lewy bodies (DLB), frontotemporal dementia, Parkinson disease, progressive supranuclear palsy, or corticobasal degeneration, with that of normals. Generalized linear mixed models were fitted with age at visit, gender, and cardiovascular factors as fixed effects and Alzheimer's Disease Centers as random effects. In late life, only BMI of ProbAD and DLB patients was statistically significantly lower than that in normals (P-values <0.001). When accounting for colinearity within cardiovascular factors, a low BMI was a comorbidity of certain dementia etiologies as compared with normals. These data support a concept of disease-specific associations with certain cardiovascular factors.

Environmental Emotional Sounds in AD Recognition of Environment al Emotional Sounds in Alzheimer’s Disease

Objective: Patients affected by Alzheimer’s disease show deficits in emotion processing and inappropriate social behaviors during emotional situations were clinically observed. Aim of our study was to explore the ability of patients with Alzheimer’s disease in ascribing emotional meaning to environmental or human emotional sounds, to understand if environmental sounds are impaired in their meaning or in their emotional attribute. Methods: Thirty participants were included in the study. The sample comprised two groups: 1) 15 patients with a diagnosis of probable Alzheimer’s disease; 2) 15 healthy comparison matched with the experimental group. Participants were submitted to a neuropsychological evaluation that included standardized (Mini-Mental State Examination, Boston Naming Test and the Token Test) and experimental tasks. The experimental battery was composed of four tasks: the Noise Recognition Task, the Emotion Naming Task, the Emotion Discrimination Task and the Sound and Emotion Association Task. These tasks were chosen to mirror ecologic situations, in which patients have to infer feelings elicited by sounds. Results: Analysis of variance showed that patients affected by Alzheimer’s disease had significantly worse performance than healthy comparison subjects (p <.001) in the experimental battery. Conclusion: The findings suggested, as expected, that Alzheimer’s Disease patients was less efficient than healthy comparison subjects in processing emotion, even if the two groups showed a similar trend. When patients have to associate visual and auditory stimuli, they have more difficulties in establishing among facial expressions the one to which the sound belong, rather than in identifying the meaning of the facial expressions or of the sounds.

Peripheral Oxidative Stress Markers in Individuals with Alzheimer's Disease with or without Cerebrovascular Disease

To the Editor: Growing evidence suggests that oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD).1, 2 A previous meta-analysis reported that a number of studies showed high lipid peroxidation marker, protein oxidation marker, and deoxyribonucleic acid and ribonucleic acid oxidation marker levels and low antioxidant levels in individuals with AD.3 Extensive lines of evidence support the role of oxidative injury in the pathogenesis of stroke and other vascular disease.4 Cerebrovascular disease (CVD), such as lacunes and white matter lesions, are common in elderly adults with AD. Although there may be some differences in oxidative damage between individuals with AD with and without CVD, there is a lack of studies examining biomarkers of oxidative damage in these individuals. In the present study, differences in peripheral oxidative stress markers between individuals with CVD with and without AD were determined, and correlations between biomarkers of oxidative damage and cognitive impairment were investigated. Sixty-nine individuals with AD without CVD (AD group) and 36 individuals with AD and CVD (AD + CVD group) were enrolled from a memory clinic. Individuals with AD had to meet the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria5 for a diagnosis of probable AD. AD with CVD was defined as typical AD associated with clinical and radiological evidence of CVD in the deep gray and white matter.6 In addition, 40 elderly individuals with no signs of cognitive impairment or CVD in the clinic were randomly chosen and used as a control group. Individuals with malignancies, severe cardiac or pulmonary disease, liver cirrhosis, renal failure, infectious disease, or disease requiring immunosuppressive therapy; current smokers; and individuals taking antioxidant supplements or vitamins were excluded. Cognitive function was assessed using the Mini-Mental State Examination (MMSE).7 Diacron reactive oxygen metabolite (dROM) levels, reflecting the amount of organic hydroperoxide, and biological antioxidant potential (BAP), measuring the ferric reducing ability of blood plasma, were measured using a free radical analyzer system (FRAS 4, Wismerll Company Ltd., Tokyo, Japan).8, 9 All analyses were performed within 48 hours of venous blood collection. Statistical analysis was conducted using Student t-tests, the chi-square test, analysis of covariance (ANCOVA), and the Spearman rank correlation test. Table 1 show participant characteristics and peripheral oxidative stress markers. The group with AD was significantly younger than the control group and had significantly more women than the control and AD + CVD groups. No significant differences in education and comorbidities such as hypertension, diabetes mellitus, dyslipidemia, and heart disease were found between the three groups. The AD and AD + CVD groups had significantly lower MMSE scores than the control group, but no significant differences in MMSE score and dementia duration were found between the AD and AD + CVD groups. ANCOVA, taking into account age and sex as covariates, showed that dROM levels were significantly higher in the AD group than in the control group and that BAP levels were significantly lower in the AD + CVD group than in the control and AD groups. As a result, BAP/dROM ratios were significantly lower in the AD and AD + CVD groups than in the control group and significantly lower in the AD + CVD group than in the AD group. MMSE scores significantly and negatively correlated with dROM levels (correlation coefficient (r) = −0.231, P = .02) and significantly and positively correlated with BAP/dROM ratios (r = 0.224, P = .02) but did not correlate significantly with BAP levels in participants with AD and AD + CVD. Oxidative damage was involved in the pathophysiology of the AD and AD + CVD groups and correlated with cognitive impairment. In particular, the AD + CVD group had greater abnormalities of oxidative stress markers, including the antioxidant defense system, than the AD group. These results suggest that intervention for oxidative stress may be appropriate for the inhibition of progression and prevention of cognitive impairment in individuals with AD, particularly for those who also have CVD. Although there may be some differences in oxidative damage between the central nervous system and peripheral tissue, measurements of peripheral oxidative stress markers may be useful for the assessment of disease progression. Conflict of Interest: The authors have no financial disclosures to declare. There are no conflicts of interest regarding this letter. Author Contributions: Hanyu, Iwamoto: study concept and design, acquisition of participants and data, data analysis and interpretation, preparation of manuscript. Hatanaka, Hirose, Fukasawa, Namioka: acquisition of patients, data analysis. Sponsor's Role: None.

Cognitive reserve and the severity of Alzheimer's disease.

Alzheimer's disease (AD) is a clinical syndrome caused by neurodegeneration and characterized by a progressive deterioration in cognitive ability and capacity for independent living. Cognitive reserve (CR) describes the capacity of the adult brain to cope with the effects of the neurodegenerative process and to minimize the clinical manifestation of pathology of dementia. The aim of this study was to evaluate the association of CR and the severity of AD. Method This study was cross-sectional. Functional and neuropsychological abilities of 75 outpatients with probable AD diagnosis were evaluated. Patients completed two questionnaires, "Participation in leisure activities throughout life" and CR Questionnaire.Result The relationship between Clinical Dementia Rating (CDR) and the level of CR was statistically significant (likelihood ratio (LR), p = 0.015).Conclusion The level of CR influenced the severity of dementia. This study suggests that AD patients with higher CR may benefit against cognitive decline after diagnosis of AD.

D-serine levels in Alzheimer's disease: implications for novel biomarker development.

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

Association Analyses of Reln Rs4298437 and Rs6943822 Polymorphisms with Alzheimer's Disease

Reelin, an extracellular signaling glycoprotein encoded by the RELN gene, plays a significant role in neuronal development and adult synaptic plasticity. Alterations in the expression of Reelin and in Reelin-mediated signaling have been implicated in the pathology of Alzheimer's disease (AD). We examined the possible role of the RELN rs4298437 and rs6943822 polymorphisms and their synergistic effect with the Apolipoprotein E ( APOE) ɛ4 allele in the development of AD. A total of 365 patients with a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria and 276 elderly, cognitively healthy control individuals were involved in the study. The genetic analyses were performed by PCR-RFLP and TaqMan real-time PCR methods. The investigated genotype distributions were in Hardy-Weinberg Equilibrium. No significant difference in mean age or in the distribution of genders between cases and controls was found. Comparison of rs4298437 genotype frequencies between AD and control groups showed no statistically significant difference (p=0.890). The frequencies of the different rs6943822 genotypes were similar in the two investigated groups (p=0.914). The interaction between the RELN and APOE polymorphisms did not contribute significantly to the logistic regression model ( p >0.1). Our study suggests no individual influence of the investigated RELN polymorphisms on the risk for developing AD. Given the involvement of Reelin in the APOE signaling pathway, a possible interaction of RELN and APOE ɛ2/ɛ3/ɛ4 polymorphisms in the prediction of AD was assessed, but no epistasis was found. This project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Clinical characteristics of loss-of-function mutations in ABCA7 in Belgian Alzheimer disease patients and families

Clinical characteristics of loss-of-function mutations in ABCA7 in Belgian Alzheimer disease patients and families

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

VL: A further case of erroneous recollection

We report a single-case study of a female patient (VL) who exhibited frequent episodes of erroneous recollections triggered by everyday events. Based on neuropsychological testing, VL was classified as suffering from mild to moderate dementia (MMSE=18) and was given a diagnosis of probable Alzheimer׳s disease. Her memory functions were uniformly impaired but her verbal abilities were generally well preserved. A structural MRI scan showed extensive areas of gray matter atrophy particularly in frontal and medial-temporal (MTL) areas. Results of experimental recognition tests showed that VL had very high false alarm rates on tests using pictures, faces and auditory stimuli, but lower false alarm rates on verbal tests. We provide a speculative account of her erroneous recollections in terms of her MTL and frontal pathology. In outline, we suggest that owing to binding failures in MTL regions, VL׳s recognition processes were forced to rely on earlier than normal stages of analysis. Environmental features on a given recognition trial may have combined with fragments persisting from previous trials resulting in erroneous feelings of familiarity and of recollection that were not discounted or edited out, due to her impaired frontal processes.