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Impaired memory is a hallmark of prodromal Alzheimer's disease (AD). Prior knowledge associated with the memoranda improves memory in healthy individuals, but we ignore whether the same occurs in early AD. We used functional MRI to investigate whether prior knowledge enhances memory encoding in early AD, and whether the nature of this prior knowledge matters. Patients with early AD and Controls underwent a task-based fMRI experiment where they learned face-scene associations. Famous faces carried pre-experimental knowledge (PEK), while unknown faces with which participants were familiarized prior to learning carried experimental knowledge (EK). Surprisingly, PEK strongly enhanced subsequent memory in healthy controls, but importantly not in patients. Partly nonoverlapping brain networks supported PEK vs. EK associative encoding in healthy controls. No such networks were identified in patients. In addition, patients displayed impaired activation in a right sub hippocampal region where activity predicted successful associative memory formation for PEK stimuli. Despite the limited sample sizes of this study, these findings suggest that the role prior knowledge in new learning might have been so far overlooked and underestimated in AD patients. Prior knowledge may drive critical differences in the way healthy elderly and early AD patients learn novel associations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.

The detection and processing of novelty plays a critical role in memory function. Despite this, relatively little is known about how novelty influences memory in Alzheimer's disease (AD). This review sought to address whether AD patients are still sensitive to novelty; whether novelty triggers memory processes as is observed in healthy subjects; and whether it is possible to promote novelty to enhance memory at the different stages of AD. The studies reviewed showed that novelty processing is mostly impaired in AD patients, whereas it can be preserved under some conditions in MCI, particularly when cognitive demands are otherwise low. We further identify outstanding questions that should be addressed in the near future in order to more robustly establish the fate of novelty processing and detection in the course of AD. Doing so would allow to improve current models of memory impairment in AD, leading to a more comprehensive view of the sources of memory decline and could lead to neuropsychological and/or pharmaceutical rehabilitation programs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Episodic memory impairment is at the core of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). The origin of memory deficits may result either from an encoding deficit or from an accelerated decline of the memory trace. The present study explores these two hypotheses., Method: We used the delayed-matching-to sample 48 items (DMS-48) memory test in a group of controls, aMCI patients, and AD patients (n= 16 in each group). The DMS-48 offers an incidental learning phase followed by three forced-choice recognition tests at three-minute, one-hour, and one-week delays. Moreover, the forced-choice test distinguishes three kinds of couple items: abstract (meaningless), paired (two similar exemplars), and unique (two different objects) items., Results: As predicted by the accelerated forgetting hypothesis, patients showed a decrease in recognition performance over time. Controls also exhibited a similar decline in performance. As predicted by the encoding deficit hypothesis, abstract items were the most poorly recognized in AD, at both the three-minute and the one-week delays. In AD, recognition of the paired items also dropped after the one-hour delay, followed by unique items after a one-week delay. Patients with aMCI exhibited a performance that was similar to controls, except for abstract items, which dropped at the one-week delay., Conclusions: These results are discussed in light of a third hypothesis, the memory strength hypothesis, in order to better account for the progressive decline in memory performance as a function of the item type in AD.

There is a large body of research on discourse production in Alzheimer's disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load. The aim of the present study was to analyze autobiographical discourse impairment in AD from a broad perspective, looking at pausing behavior (frequency, duration, and location). Our first objective was to characterize discourse changes in mild cognitive impairment (MCI) due to AD. Our second objective was to determine the cognitive and neuroanatomical correlates of these changes. Fifteen patients with MCI due to AD and 15 matched cognitively normal controls underwent an ecological episodic memory task, a full neuropsychological assessment, and a 3D T1-weighted MRI scans. Autobiographical discourse collected from the ecological episodic memory task was recorded, transcribed, and analyzed, focusing on pausing. Intergroup comparisons showed that although patients did not produce more pauses than controls overall, they did make more between-utterance pauses. The number of these specific pauses was positively correlated with patients' episodic memory performance. Furthermore, neuroimaging analysis showed that, in the patient group, their use was negatively correlated with frontopolar area (BA 10) grey matter density. This region may therefore play an important role in the planning of autobiographical discourse production. These findings demonstrate that pauses in early AD may reflect a compensatory mechanism for improving mental time travel and memory retrieval.

Unlabelled: The DMS 48 is a visual recognition memory test designed to detect memory changes in early Alzheimer's disease (AD). The aim of this study was to produce normative scores for this test and to assess its psychometric properties in the detection of AD by comparison with a widely used test of verbal episodic memory: the story recall task of the Wechsler memory scale. Methods. Data were collected in a sample of 1002 agricultural retirees, aged 65 years and over, included in the AMI study, a population-based cohort conducted in Southwestern France. The sample used to establish normative data included 750 non-demented elderly while the sample used to study the properties of the test to detect AD included 751 participants whose 34 with AD. To assess AD detection accuracy, DMS 48 was compared to the Wechsler story recall task. Results. Age, sex, and education were significantly associated with DMS 48 performances. Therefore, normative scores were calculated according to sex, age, and educational level, and described by percentiles. Regarding the test properties for AD detection, DMS 48 presented a good balance between sensitivity (Se) and specificity (Sp) both for immediate (Se=70.6%; Sp=79.6%) and delayed recall (Se=79.4%; Sp=72.9%). It also showed high negative predictive values, around 98.5% for both recalls. Detection values were roughly similar to that of Wechsler story recall task., Conclusion: The DMS 48 seems to be as reliable as the Wechsler story recall task with similar detection properties. The DMS 48 is a test easy to administer in clinical situations and could be a helpful tool for AD screening.

Purpose: AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer's disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations., Methods: We recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed., Results: White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter., Conclusion: These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications., Competing Interests: The authors declare that they have no conflict of interest.

We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45). His data were compared with those from healthy participants and patients with sporadic predemential Alzheimer disease. He exhibited posterior cortical thickness reduction, posterior hypometabolism, and increased amyloid ligand uptake in the posterior cortex and the striatum. We show that F-AV45 positron emission tomography allows visualization of the unusual pattern of amyloid deposits that co-localize with cortical atrophy in this genetic form of Alzheimer disease.

Background: In the common form of Alzheimer's disease (AD), neurofibrillary tangles, which are associated with cognitive dysfunction, initially develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before reaching the hippocampus. This area plays a key role in visual recognition memory (VRM). Impaired VRM could therefore be an early marker of AD., Methods: An extensive neuropsychological assessment including VRM tasks was performed in 26 patients with single-domain amnestic mild cognitive impairment at baseline. We evaluated the diagnostic accuracy of neuropsychological tests using ROC curve analyses in a prospective longitudinal study until conversion to probable AD or with a follow-up of at least 6 years., Results: VRM performance predicted conversion to AD with a sensitivity of 80% and a specificity of 90.9%. Combining the assessment of VRM with a verbal memory task increased diagnostic accuracy., Conclusions: Cognitive 'biomarkers' evaluating the function of brain areas that are the target of degenerative change should be considered for the early diagnosis of AD., (Copyright © 2013 S. Karger AG, Basel.)

Diagnosis of Alzheimer's disease (AD) in its earliest stages becomes increasingly important as disease modifying agents are being developed. In this area of research, many clinical and neuroimaging studies focus on markers of hippocampal dysfunction. However, during the "transentorhinal stage" of AD, neurofibrillary tangles (NFT), related to tau protein pathology, develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before the hippocampus. NFT are tightly correlated with clinical symptoms. Therefore, an accurate understanding of the behavioral correlate of transentorhinal dysfunction could critically contribute to the early diagnosis of the disease. Recent findings from studies in animals and human brain-damaged patients suggest that the anterior subhippocampal region, functionally integrated into an anterior mesiotemporal network, is involved in object based context-free memory. In this article, we evaluate the hypothesis according to which tau deposition in the anterior subhippocampal region during the earliest stages of the most common form of AD, with predominant MTL dysfunction, will lead to dysfunction of neural networks implicated in context-free memory. We challenge the view that impaired episodic memory is the hallmark of early AD. Instead, a model that integrates the localization and temporal sequence of NFT within the mesial temporal lobe (MTL) is proposed. Paralleling the development of NFT in anterior subhippocampal areas, impaired context-free, object-based, memory could be the first detectable sign in AD. In a subsequent, "hippocampal" stage, context-rich, episodic and spatial memory, becomes altered as well. The question as to the "episodic" nature of "episodic memory tasks" is also addressed.

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Purpose: Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage., Methods: We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD., Results: Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL., Conclusion: These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the "net sum" of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective.

Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment). The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

The article presents a case study of a 37-year-old man who was admitted to the hospital with complaints of progressive gait disorder followed by cognitive difficulties. His structural magnetic resonance imaging (MRI) scan revealed posterior cortical atrophy on T1 sequence. His thorough analysis revealed a higher bilateral hippocampal AV45 uptake in patient than in patients with Alzheimer's disease.