Objective: The clinical differential diagnosis of Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can no longer rely only on episodic memory impairment or executive ...dysfunctions, as highlighted by recent findings showing that both diseases could present with similar impairments. Objective cognitive tests assessing specific symptoms, such as impulsivity in bvFTD, are thus crucially needed. The aim of this study was to evaluate the differences in impulsivity between bvFTD and AD using a delay-discounting paradigm. Method: An ecological delay-discounting test was administrated to 70 participants including 30 ADs, 20 bvFTD and 20 controls. AD patients were divided according to the severity of the disease into mild or moderate group. The delay-discounting score, reflecting the total percentage of impulsive choice across the entire task, was analyzed for each group. Results: This score showed that bvFTD patients were significantly more impulsive than controls and AD patients at mild or moderate stage. AD patients, regardless of disease stage, did not differ from controls. ROC analyses revealed high and significant area under the curve (AUC, 95% confidence interval) for this score to differentiate bvFTD from AD (0.704) or controls (0.904), or both group (AD + controls; AUC = 0.791). Conclusion: The total delay-discounting score provided by our task showed that it could accurately differentiate bvFTD patients from AD and controls. These results support the relevancy of using tests inspired by experimental psychoeconomics and taping into reward processing to increase the distinction between both diseases.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Intraoperative electrical stimulation, which temporarily inactivates restricted regions during brain surgery, can map cognitive functions in humans with spatiotemporal resolution unmatched by other ...methods. Using this technique, we found that stimulation of the right inferior parietal lobule or the caudal superior temporal gyrus, but not of its rostral portion, determined rightward deviations on line bisection. However, the strongest shifts occurred with subcortical stimulation. Fiber tracking identified the stimulated site as a section of the superior occipitofrontal fasciculus, a poorly known parietal-frontal pathway. These findings suggest that parietal-frontal communication is necessary for the symmetrical processing of the visual scene.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both ...entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To prospectively evaluate the accuracy of automated hippocampal volumetry to help distinguish between patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and elderly ...controls, by using established criteria for patients with AD and MCI as the reference standard.
The regional ethics committee approved the study and written informed consent was obtained from all participants. The study included 25 patients with AD (11 men, 14 women; mean age +/- standard deviation SD, 73 years +/- 6; Mini-Mental State Examination (MMSE) score, 24.4 +/- 2.7), 24 patients with amnestic MCI (10 men, 14 women; mean age +/- SD, 74 years +/- 8; MMSE score, 27.2 +/- 1.4) and 25 elderly healthy controls (13 men, 12 women; mean age +/- SD, 64 years +/- 8). For each participant, the hippocampi were automatically segmented on three-dimensional T1-weighted magnetic resonance (MR) images with high spatial resolution. Segmentation was performed by using recently developed software that allows fast segmentation with minimal user input. Group differences in hippocampal volume were assessed by using Student t tests. To obtain robust estimates of P values, the correct classification rate, sensitivity, and specificity, bootstrap methods were used.
Significant hippocampal volume reductions were detected in all groups of patients (-32% in AD patients vs controls, P < .001; -19% in MCI patients vs controls, P < .001; and -15% in AD patients vs MCI patients, P < .01). Individual classification on the basis of hippocampal volume resulted in 84% correct classification (sensitivity, 84%; specificity, 84%) between AD patients and controls and 73% correct classification (sensitivity, 75%; specificity, 70%) between MCI patients and controls.
This automated method can serve as an alternative to manual tracing and may thus prove useful in assisting with the diagnosis of AD.
Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation ...and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.
Word finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to-lexical information which also subserves lexical-to-semantic ...mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking.
We addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture-naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical-semantic hub.
Our results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid-temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Behavioural variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease that is clinically characterised by progressive behavioural changes and social interpersonal dysfunctions. Its ...diagnosis remains a clinical challenge, and depression is one of the main causes of misdiagnoses due to the prevalence of apathy in bvFTD.
To evaluate the sensitivity and specificity of the Social Cognition and Emotional Assessment (SEA) and the mini-SEA for differentiating bvFTD from major depressive disorder (MDD).
Scores for the SEA and mini-SEA for 37 patients with bvFTD (divided into subgroups of 17 with early bvFTD and 20 with moderate bvFTD according to the normal range of the Mattis Dementia Rating Scale), 19 MDD patients and 30 control subjects were compared to define the discrimination power of these tools compared with other standard neuropsychological tests.
SEA and mini-SEA scores were significantly lower for both the early and moderate bvFTD groups compared with control subjects and the MDD group, and very few scores overlapped between patients in the bvFTD subgroups and patients in the MDD and control subgroups. SEA and mini-SEA scores distinguished early bvFTD from MDD with sensitivity and specificity rates above 94%.
Unlike standard executive neuropsychological tests, SEA and the mini-SEA can differentiate MDD from bvFTD in the early stages of the disease. The mini-SEA is an easy tool that can be utilised in neurological or psychiatric departments.
Purpose
We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with ...Alzheimer’s disease (AD) and elderly control subjects.
Materials and methods
We studied 16 patients with AD mean age ± standard deviation (SD) = 74.1 ± 5.2 years, mini-mental score examination (MMSE) = 23.1 ± 2.9 and 22 elderly controls (72.3 ± 5.0 years, MMSE = 28.5 ± 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results.
Results
We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%).
Conclusions
Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
ABSTRACT
Background: Following prescribed medication regimens is essential for the effective treatment of any medical condition. Unfortunately, patients often fail to follow recommendations, and ...treatment non-compliance represents a widespread, often underestimated problem, placing tremendous burden on the healthcare system. Compliance in Alzheimer's disease (AD), a chronic neurodegenerative disease typically afflicting older adults, is especially challenging.
Scope: To review factors contributing to poor treatment compliance in AD, considering the prominent role caregivers often play in treatment management; and acknowledging strategic approaches, particularly modern transdermal patches, to improve compliance in this particularly susceptible population. Articles were identified by searching MEDLINE in November 2006 (search limits: 1987–2007) using the terms: compliance; Alzheimer's; treatment; and transdermal. Additional resources included bibliographies of identified articles.
Findings: Strategic approaches to improving treatment compliance include: simplifying treatment regimens, using reminder packaging, and developing more patient- or caregiver-friendly modes of administration. To date, AD therapies have been administered orally. However, recent developments in alternative modes of drug delivery, such as transdermal patches, may offer effective, well-tolerated treatment options with the potential to enhance compliance. A patch containing rivastigmine (Exelon*), an established cholinesterase inhibitor, has been developed and demonstrated to have good efficacy and tolerability in patients with AD. In addition, initial caregiver experience suggests preference for the patch over oral administration.
Conclusion: Transdermal patches may be an effective way to optimize treatment compliance for AD, as well as an increasing number of other chronic conditions that typically afflict the older population, offering the possibility of more sustained clinical benefits.
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