Validation of brief cognitive tests in mild cognitive impairment, Alzheimer's disease and dementia with Lewy bodies.

Background It is estimated that 34 million people suffer from dementia, costing society US$422 billion each year. Alzheimer’s disease (AD) is the most common dementia and the global prevalence is predicted to increase to over 100 million people by the year 2050, with the greatest increase in developing countries. Therefore, inexpensive and efficient instruments are required for investigation and evaluation. Aim To evaluate the brief cognitive tests cube copying, clock drawing, the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) in the early diagnosis, treatment evaluation and differential diagnosis of dementias. Populations I. 85 patients with AD. II. 33 patients with dementia with Lewy bodies (DLB) and 66 with AD. III. 75 patients with AD. IV. 99 patients with mild cognitive impairment (MCI). Findings I. Cube copying was found useful for evaluating treatment with acetylcholinesterase inhibitors (AChEI) in patients with AD. II. Easy and quick interpretations of the MMSE, clock drawing and cube copying differentiated patients with DLB from patients with AD. III. AQT was twice as sensitive as the MMSE in detecting treatment response to AChEI in patients with AD. IV. The MMSE, AQT and clock drawing were as accurate as cerebrospinal fluid biomarkers (tau, Aβ42 and P-tau) in predicting development of AD and dementia in mild cognitive impairment during an average of five years. Conclusion This thesis has improved the validity of brief cognitive tests and contributed with results that can be clinically relevant for evaluating treatment of AD, differentiating DLB from AD, and predicting development of AD and other dementias

Dissociating memory networks in early Alzheimer's disease and frontotemporal lobar degeneration - a combined study of hypometabolism and atrophy

Introduction: We aimed at dissociating the neural correlates of memory disorders in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods: We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender. Results: Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis. Conclusion: Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by distributed networks which break down in brain degeneration

Scenery Picture Memory Test: A new type of quick and effective screening test to detect early stage Alzheimer's disease patients

It is highly desirable to develop a neuropsychological screening test which is sensitive to the early stage of Alzheimer's disease (AD), and is easy to administer at the primary care physician's (PCP's) office.Participants were 128 AD patients and 54 healthy volunteers. Brief cognitive screening tests were administered to the participants including the Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Verbal Fluency Test (VFT), a Verbal Category Cued Memory test (CCMT) and the Scenery Picture Memory Test (SPMT). In the SPMT, a scenery picture of a living room containing 23 familiar objects was used. The administration of the SPMT comprised the first shallow memory session (Pict 1) and the second deep memory session (Pict 2). The area under the receiver–operator curve (AUC) was used to compare the efficacy of SPMT with other cognitive tests.Pict 1, which requires less than 2 min to complete, had the same AUC as Pict 2, and showed significantly larger AUC than MMSE, CDT and VFT for all (MMSE 19–23) and very mild (MMSE ≥ 24) AD patients. When we conducted the similar analysis separately for those younger than 75 years and those aged 75 years or older, we obtained the same results as above among the older age group. Pict 1 showed larger AUC than CCMT in overall sample and also in the older age group, although the difference was not statistically significant.The SPMT could be useful for detection of mild and very mild AD in settings even where time is limited.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78663/1/j.1447-0594.2009.00576.x.pd

A decision support system for Rey-Osterrieth complex figure evaluation

Objective: The Rey Osterrieth complex figure (ROCF) is one of the most used neuropsychological tests for the assessment of mild cognitive impairment (MCI) and dementia. In the copy test, the patient has to draw a replica of a 18-pattern image and the outcome is a score based on the accuracy of the overall drawing. The standard scoring system however have limitations related to its subjective nature and its inability to evaluate other cognitive domains than constructional abilities. Previous works addressed those problems by proposing tablet-based automated evaluation systems. Even promising, such methods are still far away from clinical validation and translation. In this work, we developed a decision support system (DSS) for the evaluation of the ROCF copy test in the common practice using retrospective information from previously performed drawings. The goal of our system was to support the professionals providing a qualitative judgement for each of the 18 patterns, estimating the most probable diagnosis for the patient, and identifying the main signs associated to the obtained diagnosis. Methods: A total of 250 human evaluated ROCF copies were scanned from 57 healthy subjects, 131 individuals with MCI, and 62 individuals with dementia. The images were pre-processed and analysed using both computer vision and deep learning techniques to assign a qualitative label to the 18 patterns. Then, the 18 labels were used as features in 3 binary (healthy VS MCI, healthy VS dementia, MCI VS dementia) and a 3-class classifications with model explanation (SHAP).Results: Very good to excellent performance were obtained in all the diagnosis classification tasks. Indeed, an accuracy of about 85%, 91%, and 83% was obtained in discriminating healthy subjects from MCI, healthy subjects from dementia and MCI from dementia respectively. An accuracy of 73% was achieved in the 3-class classification. The model explanation showed which patterns are responsible for each prediction and how the importance of some patterns changes according to the severity of the cognitive decline. Significance: The proposed DSS enriches the standard evaluation and interpretation of the ROCF copy test. Being trained with retrospective knowledge, the performance of the DSS can be further enhanced by extending the dataset with existing ROCF copies

Executive Function Deficits in Patients with Mild Cognitive Impairment: Exploring the Impact of Substance Use

Substance use is pervasive in the United States. With overdose deaths on the rise for the past decade, studies have examined the detrimental effects of a range of substances. Substance use has been shown to affect the domains of executive functioning, while diseases such as Human Immunodeficiency Virus (HIV) and Hepatitis-C (Hep-C) have been shown to increase the severity of these deficits when comorbid with substance use. Alzheimer’s Dementia (AD) also affects many of the same domains of executive functioning as substance use. However, because of the rapid degenerative nature of the disease, individuals clinically determined to have Mild Cognitive Impairment (MCI) with a risk of progression to AD are more uniform in symptom presentation and discerned deficits, and are therefore more feasible to examine. This study examined whether a history of substance abuse impairs executive function in a cumulative manner when comorbid with MCI with a clinically indicated risk of progression to AD. While those subject to both MCI and substance use history did have the lowest scores in all of the assessments and in each of the conditions measured, those differences were insignificant. The hypothesis was not supported, even though the trend in scores was in the predicted trajectory. These results and implications are discussed, while limitations and possible future research directions are outlined

Afasia logopênica ou doença de Alzheimer : diferentes fases da mesma doença?

The logopenic variant of Primary Progressive Aphasia, or logopenic aphasia, is a the most recently described variant of Primary Progressive Aphasia and also the least well defined. This variant can present clinical findings that are also common to Alzheimer’s disease, given they both share the same cytopathologic findings. This article reports the clinical case of a patient for whom it proved difficult to define a clinical diagnosis, being split between the logopenic variant and Alzheimer’s disease at different phases of the disease. Using this case as an example and drawing on the latest evidence from the literature on the logopenic variant, we postulate the hypothesis that this variant may present as an initial symptom of Alzheimer’s disease in some atypical cases.A variante logopênica da Afasia Progressiva Primária, ou afasia logopênica, é a variante mais recentemente descrita entre todas as variantes da Afasia Progressiva Primária e, também por isso, a menos definida. Essa variante pode apresentar achados clínicos em comum com a doença de Alzheimer pelo fato de compartilharem o mesmo achado citopatológico. Este artigo descreve o caso clínico de uma paciente na qual se evidenciou uma dificuldade em assumir o diagnóstico clínico que se dividia entre a variante logopênica e a doença de Alzheimer em determinadas fases da doença. Utilizando este caso como exemplo e as atuais evidências que a literatura apresenta sobre a variante logopênica, levantamos a hipótese de que essa variante pode apresentar-se como uma manifestação inicial da doença de Alzheimer em alguns casos menos típicos

A Bayesian network decision model for supporting the diagnosis of dementia, Alzheimer׳s disease and mild cognitive impairment

AbstractPopulation aging has been occurring as a global phenomenon with heterogeneous consequences in both developed and developing countries. Neurodegenerative diseases, such as Alzheimer׳s Disease (AD), have high prevalence in the elderly population. Early diagnosis of this type of disease allows early treatment and improves patient quality of life. This paper proposes a Bayesian network decision model for supporting diagnosis of dementia, AD and Mild Cognitive Impairment (MCI). Bayesian networks are well-suited for representing uncertainty and causality, which are both present in clinical domains. The proposed Bayesian network was modeled using a combination of expert knowledge and data-oriented modeling. The network structure was built based on current diagnostic criteria and input from physicians who are experts in this domain. The network parameters were estimated using a supervised learning algorithm from a dataset of real clinical cases. The dataset contains data from patients and normal controls from the Duke University Medical Center (Washington, USA) and the Center for Alzheimer׳s Disease and Related Disorders (at the Institute of Psychiatry of the Federal University of Rio de Janeiro, Brazil). The dataset attributes consist of predisposal factors, neuropsychological test results, patient demographic data, symptoms and signs. The decision model was evaluated using quantitative methods and a sensitivity analysis. In conclusion, the proposed Bayesian network showed better results for diagnosis of dementia, AD and MCI when compared to most of the other well-known classifiers. Moreover, it provides additional useful information to physicians, such as the contribution of certain factors to diagnosis

Macro-Level Cognitive and Linguistic Function in Early Stage Alzheimer’s Disease and Mild Cognitive Impairment

Alzheimer’s disease (AD) is a global health concern, particularly as there is currently no cure for the disease. Interventions to slow progression of disease, pharmacological or non-pharmacological, need to be targeted early on before any significant neurodegeneration has occurred, as these changes are irreversible, and lost cognitive function cannot be recovered. This makes it imperative to detect pathological cognitive decline as early as possible. Although biomarkers have received a lot of attention in this regard, they have several limitations, particularly outside of research settings, such as cost and availability. Cognitive markers, other than traditional neuropsychological test measures, on the other hand, have received comparatively less attention with regards to early detection; and, particularly cognitive markers that are rooted in real-world, everyday cognition, have been lacking. Due to the disease being incurable, interventions are aimed at maintaining independent living and good quality of life for as long as possible. This necessitates outcomes that can measure meaningful change in cognition and everyday functioning. The goal of the present dissertation was to identify gaps in the current literature on cognitive and linguistic assessments that are embedded in aspects of everyday cognition in AD, and work towards developing paradigms to address the gaps. Due to the emphasis on early detection, the work focused on patients in the very early stage of AD and on its preceding stage of Mild Cognitive Impairment (MCI). In light of evidence reporting the inability of AD patients to follow narratives, be it verbal or non-verbal, a systematic review of text comprehension studies was conducted to characterize and evaluate macro-level measures of discourse comprehension in their sensitivity to early stage AD, and their ability to distinguish pathological ageing due to AD or MCI from cognitive ageing. Results showed that, not only AD patients, but also MCI patients were significantly more impaired on macro-level measures of comprehension compared to cognitively healthy older adults. These findings were consistent across all eight studies included in the review, indicating a robust effect, though there were minor differences in the sensitivity of different measures. Next, moving towards non-verbal narratives, a novel picture-based paradigm assessing event cognition, with a focus on event integration and macro-event recognition, was introduced. This study aimed to examine the macro-level processing of events by using a format requiring integration of micro-events, depicted in pictures, into a larger macro-event. AD and MCI patients’ ability to connect the micro-events temporally and causally to identify the depicted macro-event was assessed. As hypothesized, the findings showed that patient groups had significant difficulties in determining temporal order of micro-events, even when provided with a verbal cue, as well as in conceptualizing the macro-event from the presented micro-events, when compared to healthy older adults. Finally, using traditional neuropsychological tests, the cognitive processes involved in performing the macro-event recognition task were determined by examining correlations. Primarily, semantic memory and executive functioning appear to play a role. However, the strength of correlations was fairly moderate, indicating added value of event recognition task in cognitive assessment. Taken together, these findings show the sensitivity of macro-level cognitive and linguistic markers based in everyday cognition in the early stages of AD, and highlight the positive role of such cognitive assessment methods in bringing together objective assessment methods and everyday cognition