Abilities In Alzheimer's Disease Research Articles

8-weeks aerobic exercise ameliorates cognitive deficit and mitigates ferroptosis triggered by iron overload in the prefrontal cortex of APP Swe/PSEN 1dE9 mice through Xc-/GPx4 pathway.

Alzheimer's disease (AD) is a degenerative disorder of the central nervous system characterized by notable pathological features such as neurofibrillary tangles and amyloid beta deposition. Additionally, the significant iron accumulation in the brain is another important pathological hallmark of AD. Exercise can play a positive role in ameliorating AD, but the mechanism is unclear. The purpose of the study is to explore the effect of regular aerobic exercise iron homeostasis and lipid antioxidant pathway regarding ferroptosis in the prefrontal cortex (PFC) of APP Swe/PSEN 1dE9 (APP/PS1) mice. Eighty 6-month-old C57BL/6 J and APP/PS1 mice were divided equally into 8-weeks aerobic exercise groups and sedentary groups. Subsequently, Y-maze, Morris water maze test, iron ion detection by probe, Western Blot, ELISA, RT-qPCR, HE, Nissle, Prussian Blue, IHC, IF, and FJ-C staining experiments were conducted to quantitatively assess the behavioral performance, iron levels, iron-metabolism-related proteins, lipid antioxidant-related proteins and morphology in each group of mice. In APP/PS1 mice, the increase in heme input proteins and heme oxygenase lead to the elevated levels of free iron in the PFC. The decrease in ferritin content by ferritin autophagy fails to meet the storage needs for excess free iron within the nerve cells. Ultimately, the increase of free ferrous iron triggers the Fenton reaction, may lead to ferroptosis and resulting in cognitive impairment in APP/PS1 mice. However, 8-weeks aerobic exercise induce upregulation of the Xc-/GPx4 pathway, which can reverse the lipid peroxidation process, thereby inhibiting ferroptosis in APP/PS1 mice. 8 weeks aerobic exercise can improve learning and memory abilities in AD, upregulate GPx4/Xc- pathway in PFC to reduce ferroptosis induced by AD.

Electrical brain networks before and after transcranial pulsed shockwave stimulation in Alzheimer's patients.

Alzheimer's disease (AD) is a neurodegenerative disorder that dramatically affects cognitive abilities and represents the most common cause of dementia. Currently, pharmacological interventions represent the main treatment to deal with the symptoms of AD; however, alternative approaches are readily sought. Transcranial pulse stimulation (TPS) is an emerging non-invasive neuromodulation technique that uses short, repetitive shockwaves with the potential to provide a wide range of vascular, metabolic, and neurotrophic changes and that has recently been shown to improve cognitive abilities in AD. This exploratory study aims to gain insight into the neurophysiological effect of one session of TPS in AD as reflected in electroencephalographic measures, e.g., spectral power, coherence, Tsallis entropy (TE), and cross-frequency coupling (cfc). We document changes in power (frontal and occipital), coherence (frontal, occipital and temporal), and TE (temporal and frontal) as well as changes in cfc (parietal-frontal, parietal-temporal, frontal-temporal). Our results emphasize the role of electroencephalographic measures as prospective markers for the neurophysiological effect of TPS.

The use of virtual reality as a perspective-taking manipulation to improve self-awareness in Alzheimer's disease.

Lack of awareness of symptoms or having a condition referred to as anosognosia is a common feature of individuals with Alzheimer's Disease (AD). Previous literature on AD reported difficulties in evaluating self-abilities, often showing underestimation of limitations. There is increasing evidence that the perspective through which information is presented may moderate the performance appraisal and that anosognosia in AD might be a consequence of a deficit in assuming a third-person perspective. In this context, some studies showed that subjects may better recognize self-and other-difficulties when exposed to a third-person perspective. Considering the variety of approaches aiming to investigate the lack of awareness, there is still a scarcity of methods that provide great ecological validity and consider more than one facet of awareness, thus failing to offer more accurate evaluations of daily experiences. The present paper primarily addresses the theme of the multidimensional character of awareness of abilities in AD and the effect of perspective-taking on its trajectories. The focus turns to virtual reality as a promising tool for a greater evaluation of perspective-taking and self-awareness. Particularly, these systems offer the possibility to involve users in cognitive and sensorimotor tasks that simulate daily life conditions within immersive and realistic environments, and a great sense of embodiment. We propose that virtual reality might allow a great level of complexity, veracity, and safety that is needed for individuals with AD to behave according to their actual abilities and enable to explore the liaison between the subject's viewpoint, performance, and self-evaluation. In addition, we suggest promising clinical implications of virtual reality-based methods for individualized assessments, investigating specific impacts on subjects' life and possible improvements in their awareness.

Time-Based and Event-Based Prospective Memory in Mild Cognitive Impairment and Alzheimer's Disease Patients: A Systematic Review and Meta-analysis.

Prospective memory (PM) is the ability to remember to perform planned actions in a future moment and it is of fundamental importance for an independent and autonomous lifestyle from development to late adulthood. Deficits in episodic memory and executive functions, which are involved in PM are characteristic features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Considering that the number of older adults is drastically increasing over the next decades, it is of great interest to understand how PM decline in healthy older adults and patients with different degree of cognitive decline. The present meta-analysis included 46 studies investigating PM performance in AD patients (17 studies) and people with MCI (24 studies); 5 studies included both clinical conditions in the same article. The 46 studies contributed a total of 63 independent samples and 129 effect sizes from 4668 participants (2115 patients and 2553 controls). Unlike previous reviews of the literature, our results with a larger and updated sample of studies confirmed lower PM abilities in AD compared to MCI and controls, although we did not observe conclusive differences between event-based and time-based PM in patients. Surprisingly, PM deficits shown by MCI and AD patients have decreased across years, in parallel to a reduction of the evidence of publication bias and an increase in the number of observations per task. We propose the use of more reliable research designs as one plausible explanation for the reduction of PM impairments.

Methodologies for assessing morphosyntactic ability in people with Alzheimer's disease.

The detection and description of language impairments in neurodegenerative diseases like Alzheimer's Disease (AD) play an important role in research, clinical diagnosis and intervention. Various methodological protocols have been implemented for the assessment of morphosyntactic abilities in AD; narrative discourse elicitation tasks and structured experimental tasks for production, offline and online structured experimental tasks for comprehension. Very few studies implement and compare different methodological protocols; thus, little is known about the advantages and disadvantages of each methodology. To discuss and compare the main behavioral methodological approaches and tasks that have been used in psycholinguistic research to assess different aspects of morphosyntactic production and comprehension in individuals with AD at the word and sentence levels. A narrative review was conducted through searches in the scientific databases Google Scholar, Scopus, Science Direct, MITCogNet, PubMed. Only studies written in English, that reported quantitative data and were published in peer-reviewed journals were considered with respect to their methodological protocol. Moreover, we considered studies that reported research on all stages of the disease and we included only studies that also reported results of a healthy control group. Studies that implemented standardized assessment tools were not considered in this review. The main narrative discourse elicitation tasks implemented for the assessment of morphosyntactic production include interviews, picture-description and story narration, whereas the main structured experimental tasks include sentence completion, constrained sentence production, sentence repetition and naming. Morphosyntactic comprehension in AD has been assessed with the use of structured experimental tasks, both offline (sentence-picture matching, grammaticality judgment) and online (cross-modal naming,speeded sentence acceptability judgment, auditory moving window, word detection, reading). For each task we considered studies that reported results from different morphosyntactic structures and phenomena in as many different languages as possible. Our review revealed strengths and weaknesses of these methods but also directions for future research. Narrative discourse elicitation tasks as well as structured experimental tasks have been used in a variety of languages, and have uncovered preserved morphosyntactic production but also deficits in people with AD. A combination of narrative discourse elicitation and structured production tasks for the assessment of the same morphosyntactic structure has been rarely used. Regarding comprehension, offline tasks have been implemented in various languages, whereas online tasks have been mainly used in English. Offline and online experimental paradigms have often produced contradictory results even within the same study. The discrepancy between the two paradigms has been attributed to the different working memory demands they impose to the comprehender or to the different parsing processes they tap. Strengths and shortcomings of each methodology are summarized in the paper, and comparisons between different tasks are attempted when this is possible. Thus, the paper may serve as a methodological guide for the study of morphosyntax in AD and possibly in other neurodegenerative diseases. What is already known on this subject For the assessment of morphosyntactic abilities in AD, various methodological paradigms have been implemented: narrative discourse elicitation tasks and structured experimental tasks for production, and offline and online structured experimental tasks for comprehension. Very few studies implement and compare different methodological protocols; thus, little is known about the advantages and disadvantages of each methodology. What this paper adds to existing knowledge The paper presents an overview of methodologies that have been used to assess morphosyntactic production and comprehension of people with AD at the word and sentence levels. The paper summarizes the strengths and shortcomings of each methodology, providing both the researcher and the clinician with some directions in their endeavour of investigating language in AD. Also, the paper highlights the need for further research that will implement carefully scrutinized tasks from various experimental paradigms and will explore distinct aspects of the AD patients' morphosyntactic abilities in typologically different languages. What are the potential or actual clinical implications of this work? The paper may serve as a reference point for (psycho-)linguists who wish to study morphosyntactic abilities in AD, and for speech and language therapists who might need to apply morphosyntactic protocols to their patients in order to assess them or design appropriate therapeutic interventions for production and comprehension deficits.

Protein Kinase C Involvement in Neuroprotective Effects of Thymol and Carvacrol Against Toxicity Induced by Amyloid-β in Rat Hippocampal Neurons.

We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer Disease (AD) rat models. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death induced by Aβ25-35 can be protected by thymol and carvacrol via Protein Kinase C (PKC) and Reactive Oxygen Species (ROS) pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in the AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKCα were examined in the hippocampal cells of the AD rat model. To examine the thymol and carvacrol effects, we performed a behavioral test in AD rat models induced by Aβ25-35 neurotoxicity. To access the underlying mechanism of the protective effects, western blotting was performed with antibodies against PKCα. We also measured the PKC activity assay by Elisa. Histopathological studies were carried out in the hippocampus with Hematoxylin and Eosin (H&E) staining. The escape latency increased in Aβ-received rats compared to the control group, and thymol and carvacrol reversed this deficit. Furthermore, these compounds could enhance the PKC activity and increase the PKCα expression ratio. Moreover, H&E staining showed that Aβ caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of Aβ peptides. This study suggests that Amyloid-Beta (Aβ) results in memory decline and histochemical disturbances in the hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation. Rat's ability to find the invisible platform in the Morris Water Maze (MWM) was impaired by Amyloid-Beta (Aβ) infusion in the hippocampus, while this effect was reversed by thymol or carvacrol administration.Aβ significantly downregulated the Protein Kinase C (PKC) activity in rats' hippocampus.Western blot analysis demonstrated that Aβ significantly reduced PKCα protein expression in AD rat model hippocampal cells.The expression ratio of PKCα was upregulated following the injection of thymol and carvacrol in rats.Injection of Aβ in the hippocampus resulted in histochemical disturbances in CA1 pyramidal neurons.Carvacrol and thymol can prevent several histological changes induced by Aβ. Alzheimer's disease is one of the most important brain diseases in which the learning and memory are impaired. One of the main causes of Alzheimer's disease is the presence of amyloid beta plaques in the neurons. Protein kinase C enzyme reduces amyloid production and accumulation in the brain. In the present study, we tested the possible effects of carvacrol and thymol in a rat model of Alzheimer's disease. Memory impairment was induced in adult rats by intra-cerebral infusion of amyloid β. One week later, the memory-impaired animals were treated with carvacrol and thymol. Finally, we tested their memory in a Morris water maze apparatus. Furthermore, their hippocampus was dissected and PKC activity and the neuronal injury was evaluated. Our findings exhibited that thymol and carvacrol improved rats' memory performance. In addition, thymol and carvacrol significantly increased PKC activity and prevented neuronal cell loss in the rat hippocampus. This study shows that thymol and carvacrol have beneficial effects on memory and cognitive function via PKC activation.

Peripheral reaching in Alzheimer's disease and mild cognitive impairment

Recent evidence has implicated areas within the posterior parietal cortex (PPC) as among the first to show pathophysiological changes in Alzheimer's disease (AD). Focal brain damage to the PPC can cause optic ataxia, a specific deficit in reaching to peripheral targets. The present study describes a novel investigation of peripheral reaching ability in AD and mild cognitive impairment (MCI), to assess whether this deficit is common among these patient groups. Individuals with a diagnosis of mild-to-moderate AD, or MCI, and healthy older adult controls were required to reach to targets presented in central vision or in peripheral vision using two reaching tasks; one in the lateral plane and another presented in radial depth. Pre-registered case–control comparisons identified 1/10 MCI and 3/17 AD patients with significant peripheral reaching deficits at the individual level, but group-level comparisons did not find significantly higher peripheral reaching error in either AD or MCI by comparison to controls. Exploratory analyses showed significantly increased reach duration in both AD and MCI groups relative to controls, accounted for by an extended Deceleration Time of the reach movement. These findings suggest that peripheral reaching deficits like those observed in optic ataxia are not a common feature of AD. However, we show that cognitive decline is associated with a generalised slowing of movement which may indicate a visuomotor deficit in reach planning or online guidance.

Reduced Contextual Information During Future Thinking in Alzheimer's Disease.

This study assessed the ability of patients with Alzheimer's Disease (AD) to produce "when, where, and who" information during future thinking. AD patients and control participants were invited to imagine future scenarios. Future thinking was analyzed with respect to the number of "when, where, and who" details. Analysis showed fewer "when, where, and who" details in AD participants than in control participants. Fewer "when" than "where" details and fewer "where" than "who" details were observed in AD and control participants. Production of temporal information in participants with AD was found to be associated with general cognitive functioning, as assessed with the Mini Mental State Exam. Future thinking in AD is mainly associated with reduced contextual information. The diminished ability to construct time-related details during future thinking in AD can be mainly associated with the diminished general cognitive ability in AD, and probably with hippocampal compromise in the disease. We also propose a socio-emotional account according to which, confronted with a limited-time perspective during future thinking, AD patients may tend to maximize their emotional well-being by avoiding time-related information and thinking about friends, family and beloved ones.

Temporal dynamic changes of intrinsic brain activity in Alzheimer’s disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory impairment. Previous studies have largely focused on alterations of static brain activity occurring in patients with AD. Few studies to date have explored the characteristics of dynamic brain activity in cognitive impairment, and their predictive ability in AD patients.MethodsOne hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (HC) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) and the dynamic fraction amplitude of low-frequency fluctuation (dfALFF) were used to assess the temporal variability of local brain activity in patients with AD or mild cognitive impairment (MCI). Pearson’s correlation coefficients were calculated between the metrics and subjects’ behavioral scores.ResultsThe results of analysis of variance indicated that the AD, MCI, and HC groups showed significant variability of dALFF in the cerebellar posterior and middle temporal lobes. In AD patients, these brain regions had high dALFF variability. Significant dfALFF variability was found between the three groups in the left calcarine cortex and white matter. The AD group showed lower dfALFF than the MCI group in the left calcarine cortex.ConclusionsCompared to HC, AD patients were found to have increased dALFF variability in the cerebellar posterior and temporal lobes. This abnormal pattern may diminish the capacity of the cerebellum and temporal lobes to participate in the cerebrocerebellar circuits and default mode network (DMN), which regulate cognition and emotion in AD. The findings above indicate that the analysis of dALFF and dfALFF based on functional magnetic resonance imaging data may give a new insight into the neurophysiological mechanisms of AD.

Betaine Alleviates Cognitive Deficits in Diabetic Rats via PI3K/Akt Signaling Pathway Regulation

Background: Diabetes mellitus is a metabolic disease which also causes cognitive deficits. Betaine (N,N,N-trimethylglycine), also known as trimethylglycine, has been shown to ameliorate diabetic symptoms in diabetic animals and improve cognitive ability in Alzheimer disease (AD) animals. However, the effects of betaine on cognitive deficits in diabetic animals have not been described yet. Therefore, in the current study, the effects of betaine on cognition in diabetic rats were evaluated. Methods: We established a diabetic rat model by injecting streptozotocin (STZ) into rats and administrated betaine to these diabetic rats. We monitored the metabolism index, and glucose and insulin levels in blood and cerebrospinal fluid. We measured inflammatory cytokine levels, including TNF-α, IL-1β, and IL-6, in serum and hippocampus. We also monitored oxidative stress in the hippocampus by measuring malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. We measured the learning and memory ability of diabetic rats using the Morris water and Y maze tests and tested the phosphatidylinositol 3-kinase (PI3K)/Akt activation and p-mTOR level in the hippocampus. Results: Betaine improved glucose metabolism and suppressed the production of inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Also, betaine decreased MDA concentration and increased SOD activity in the hippocampus of diabetic rats. Betaine ameliorated cognitive deficits in diabetic rats, and it promoted PI3K expression and Akt activation and decreased p-mTOR expression. Conclusion: Betaine alleviates cognitive deficits in STZ-induced diabetic rats via regulating the PI3K/Akt signaling pathway.

Distinct structural correlates of the dominant and nondominant languages in bilinguals with Alzheimer's disease (AD)

Structural adaptations in brain regions involved in domain-general cognitive control are associated with life-long bilingualism and may contribute to the executive function advantage of bilinguals over monolinguals. To the degree that these adaptations support bilingualism, their disruption by Alzheimer's disease (AD) may compromise the ability to maintain proficiency in two languages, particularly in the less proficient, or nondominant, language that has greater control demands. The present study assessed this possibility in Spanish-English bilinguals with AD (n = 21) and cognitively normal controls (n = 30) by examining the brain correlates of dominant versus nondominant language performance on the Multilingual Naming Test (MINT), adjusting for age and education. There were no significant structural correlates of naming performance for either language in controls. In patients with AD, dominant language MINT performance was associated with cortical thickness of the entorhinal cortex and middle temporal gyrus, consistent with previous findings of temporal atrophy and related decline of naming abilities in AD. Nondominant language MINT performance, in contrast, was correlated with thickness of the left caudal anterior cingulate cortex (ACC), a central cognitive control region involved in error monitoring and task switching. The relationship between naming in the nondominant language and ACC in patients with AD but not in controls may reflect increased reliance on the ACC for nondominant language use in the face of atrophy of other control network components. The results are consistent with the possibility that the increased burden nondominant language use places on cognitive control systems compromised in AD may account for faster nondominant than dominant language decline in AD.

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Purpose of the researchAlthough single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks.Principal resultsCognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (ρ = 0.304; p = .004) and genetic interaction-associated FC in ECN (ρ = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc).Major conclusionsThese findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.

Neural basis of visual perception and reasoning ability in Alzheimer's disease: correlation between Raven's Colored Progressive Matrices test and 123 I-IMP SPECT imaging results.

Impairment of visual perception frequently occurs in Alzheimer's disease (AD) and can cause severe constraints in daily activities. The nonverbal Raven's Colored Progressive Matrices (RCPM) test consists of sets A, AB, and B and is easily performed in a short time to evaluate both visual perception and reasoning ability. The purpose of this study was to evaluate the neural basis of visual perception and reasoning ability in patients with AD using RCPM and single-photon emission computed tomography (SPECT). Fifty patients who fulfilled the National Institute on Aging/Alzheimer's Association criteria for probable AD dementia were examined with RCPM and SPECT. All SPECTs were performed using N-isopropyl-p-[123 I]-iodoamphetamine. A multiple regression model was used to perform multivariate analyses of the relationships between regional cerebral blood flow (rCBF) and RCPM scores. There was a significant positive correlation between RCPM total score and rCBF in the inferior parietal lobes bilaterally, the right inferior temporal gyrus, and the right middle frontal gyrus. Set A was positively correlated with rCBF in the right temporal and right parietal lobes. Set AB was positively correlated with rCBF in the right temporal, right parietal, and right frontal lobes. Set B was positively correlated with rCBF in the right parietal and right frontal lobes. Our findings suggest that deteriorations of specific brain regions are associated with dysfunction of visual perception and reasoning ability in AD. RCPM is another informative assessment scale of cognition for use in patients with AD. Copyright © 2016 John Wiley & Sons, Ltd.

TrkB activation by 7, 8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer's disease.

We recently demonstrated that activation of tyrosine receptor kinase B (TrkB) by 7, 8-dihydroxyflavone (7, 8-DHF), the selective TrkB agonist, increased surface alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPARs) AMPA receptor subunit GluR1 (GluA1) subunit expression at the synapses of Fragile X Syndrome mutant mice. This present study investigated the effects of 7, 8-DHF on both memory function and synapse structure in relation to the synapse protein level of AMPARs in the Tg2576 Alzheimer's disease (AD) mouse model. The study found that chronic oral administration of 7, 8-DHF significantly improved spatial memory and minimized dendrite loss in the hippocampus of Tg2576 mice. A key feature of 7, 8-DHF action was the increased expression of both GluA1 and GluA2 at synapses. Interestingly, 7, 8-DHF had no effect on the attenuation of amyloid precursor protein or Aβ exhibiting in the Tg2576 AD brains, yet it activated the phosphorylation of TrkB receptors and its downstream signals including CaMKII, Akt, Erk1/2, and cAMP-response element-binding protein. Importantly, cyclotraxin B (a TrkB inhibitor), U0126 (a Ras-ERK pathway inhibitor), Wortmannin (an Akt phosphorylation inhibitor), and KN-93 (a CaMKII inhibitor) counteracted the enhanced expression and phosphorylation of AMPAR subunits induced by 7, 8-DHF. Collectively, our results demonstrated that 7, 8-DHF acted on TrkB and resolved learning and memory impairments in the absence of reduced amyloid in amyloid precursor protein transgenic mice partially through improved synaptic structure and enhanced synaptic AMPARs. The findings suggest that the application of 7, 8-DHF may be a promising new approach to improve cognitive abilities in AD. We provided extensive data demonstrating that 7, 8-dihydroflavone, the TrkB agonist, improved Tg2576 mice spatial memory. This improvement is correlated with a reversion to normal values of GluA1 and GluA2 AMPA receptor subunits and dendritic spines in CA1. This work suggests that 7, 8-DHF is a suitable drug to potentiate in vivo Tropomyosin receptor kinase B (TrkB) signaling in the Alzheimer's disease mice model.

Visual-motor embodiment of language: a few implications for the neuropsychological evaluation (in Alzheimer's disease).

For several decades, researchers in cognitive neuroscience and cognitive psychology have developed works concerning the close relationships between “lower-level” perceptual/motor and “higher-level” conceptual/linguistic processes (Harnad, 1987; Goldstone, 1994; Barsalou, 1999; Pulvermuller and Fadiga, 2010). Some of them suggested to “reunit” perception and conception (Goldstone and Barsalou, 1998), studied the interactions between language and action (Glenberg and Kaschak, 2002; see Pulvermuller and Fadiga, 2010, for a global picture in neuroscience), or were interested in the relationships between language and other bodily (emotional) states (Glenberg et al., 2005). On the neurophysiological and ophthalmological grounds, contemporary studies suggest that not only does Alzheimer's Disease (AD) lead to alteration in brain cortical structure and cognitive impairment, but it also conducts to deep changes in both visual system organization and vision-based performances (Tzekov and Mullan, 2013). We recommend that both the perceptual impairment found in AD and the interactions between lower-level and higher-level cognition be taken into account by neurospychologists in order to avoid misattribution of performance deficits. We first mention a recent research concerning language evaluation in AD and discuss main limitations of modular evaluation in that type of context. Then, we present main features of the visual “function” impairment in AD, the impacts of perceptual changes over higher-level cognition, and finally, we provide general recommendations for neuropsychological testing of higher-level cognitive “functions”. Linguistic evaluation in AD Drummond et al. (2015) reported an interesting research in which language production processes were evaluated in patients with AD, amnestic mild cognitive impairment (a-MCI), and controls. In contrast with many neuropsychological tests aiming at evaluating language on the basis of simple concept production (e.g., naming), the authors developed a “narrative test,” in which participants were supposed to narrate a story from a sequence of visually presented actions. Overall, the authors found that patients with a-MCI already presented narrative deficits in comparison with the control group. Interestingly, a-MCI discursive deficits were lower than those presented by patients with AD, which may be interpreted as an intermediate level of deficiency between healthy elderly and patients with AD. The research is interesting and allows us to examine usual practices in neuropsychology and neuropsychological research. Although the participants in this kind of research generally undergo both neuropsychological and visual (i.e., acuity) assessments, the real involvement of language “function” in the deficits found in patients with AD or a-MCI can be questioned. As we will see later, AD can lead to several visual processing impairments that influence higher-level cognitive performance so that checking for normal or corrected-to-normal visual acuity is not sufficient to control for lower-level influence on cognitive performance. Typically, whether in neuropsychology or in speech therapy, language abilities in AD are often evaluated by tests involving the visual “function”. For instance, in the naming tests, patients have to orally produce the word represented by a drawing picture. Similarly, oral comprehension tests ask patients to indicate, among several pictures, which corresponds to a word or a sentence read by the examiner. In other words, patients have to visually recognize a picture (as in the naming tests) based on an oral description. The matching category tests also require patients to choose—among several visual items—the one that is semantically associated with a target item. Finally, tests that focus on graphic abilities (e.g., dictation, free writing, writing description) also rely on visual “functions”. When performances are altered in the tests such as those described above, any earlier level of information processing can be involved (Greene, 2005). Although they are mainly employed to evaluate language, these tests can also reflect visual “function” impairment. The semantic recognition of drawings or pictures implies that patients rely on good visual acuity, color vision, contrast sensitivity, and oculomotor processing. Misinterpretations of AD patient troubles may arise if visual performances are not taken into account (and controlled for in statistical analyses).

Neuropsychological Deficits Associated With Route Learning in Alzheimer Disease, MCI, and Normal Aging

The background of route learning (RL) abilities in Alzheimer disease (AD), mild cognitive impairment (MCI), and normal aging needs further study. We searched for neuropsychological and demographical predictors of RL impairment. RL was investigated in a clinical study including subjects classified as early AD (n=37), MCI (n=34), and aged normal controls (n=46). An ecological assessment procedure of RL was employed and landmarks learning and navigational abilities were evaluated. The consortium to establish a registry of Alzheimer's disease test battery was used for neuropsychological assessment. Almost all AD patients, and most subjects with MCI misidentified landmarks and made navigational errors when following the route without assistance. Moreover, a small subgroup of normal controls also had problems with RL. Poor RL performance was best predicted by impairments in memory and executive functions. RL impairment is common in early AD and MCI, and is occasionally also found in normal elderly subjects. Its characteristic appearance is a combination of poor landmark recognition and defective directional guidance. Poor RL can be predicted by neuropsychological testing. In MCI and in a subset of normal aged persons, RL impairment may herald incipient dementia.

Functional dementia assessment using a video monitoring system: Proof of concept

Functional assessments of a person’s ability to perform activities of daily living (ADL) currently involves clinical rating scales. These scales are limited in providing objective and sensitive information. Aim To develop an automated tool for objective and quantitative assessment of functional ability in Alzheimer disease (AD). Methods 16 Patients with mild to moderate AD (age=76.7±4.0, MMSE=20,7±2.0) and 10 age and gender matched healthy controls (HC; age=73.9±4.5, MMSE=28.1±1.3) were evaluated clinically, cognitively, and functionally. Subsequently, each subject was asked to perform a set of daily tasks while monitored by two video cameras. A measure of functional impairment was then computed from quantitative and qualitative parameters collected from video recordings that were first annotated by two clinicians (blind to each other results and the participants’ clinical state). Results The VMS (Video monitoring system) function index (derived from a ratio of efficacy in ADLs) correlated strongly with cognitive results (MMSE, Rho=0.81) as well as with IADL-E scores (Rho=-0.65). Conclusion This study is a successful proof of concept for a novel assessment tool in dementia. The derived VMS function-index may provide a pragmatic, objective and continuous measure of cognitive and functional ability for clinical assessments as well as having a role as an outcome measure in clinical trials. Future research should complete the automation of the method.

Association between cerebral metabolism and Rey–Osterrieth Complex Figure Test performance in Alzheimer's disease

The copy condition of the Rey–Osterrieth Complex Figure (ROCF) is sensitive to Alzheimer's disease (AD) pathology, but its neural correlates remain unclear. We used fluorodeoxyglucose positron emission tomography (FDG–PET) to elucidate this association in 77 patients with probable AD. We observed a correlation between ROCF and metabolic rate of bilateral temporal–parietal cortex and occipital lobe, and right frontal lobe. Global and local elements of the ROCF correlated with metabolic rate of these same regions. The copy approach correlated with right lateral temporal cortex. The ROCF appears reflective of posterior temporal–parietal cortex functioning, highlighting the role of visuospatial processing in constructional abilities in AD.

Impact of Subcortical Hyperintensities on Dual-tasking in Alzheimer Disease and Aging

Subcortical hyperintensities (SHs) on brain magnetic resonance imaging are associated with cognitive and gait impairment in elderly but their impact on dual-tasking (performing cognitive tasks while walking) in patients with Alzheimer disease (AD) is unknown. This study explored the costs of dual-tasking in relation to SH severity in AD and normal controls (NCs). Cadence while walking on a treadmill, and speed-accuracy-tradeoff (SAT), on 3 working memory tasks, were measured during single-task and dual-task conditions. Dual-task costs (DTC) on SAT, cadence, and overall DTC were measured for each of these tasks. On visual rating of SH severity, AD and NC groups were subdivided into high-SH and low-SH subgroups. Compared with the NC, the AD group performed poorly on all working memory tasks across both conditions, decreased cadence on dual-tasking, and showed a decrement in overall DTC (all P<0.01). When grouped according to SH severity, the low-SH-NC group performed superiorly on working memory tasks (P<0.001) and the high-SH-AD group (P=0.001) showed a decrease in dual-task costs of cadence. Although the AD group showed a decrement in overall DTC (P<0.01) compared with NC, when assessed in terms of SH severity, the high-SH-AD group showed the largest decrement in DTC (P<0.01). Greater SH severity is associated with a decrement in overall dual-tasking ability in AD.

Dislipemia y demencia

Cholesterol, omega 3 fatty acids and triglycerides may influence cognitive abilities in Alzheimer disease (AD) and other types of dementia. Epidemiological studies suggest an important role of cholesterol in the regulation of beta-amyloid protein (Aβ), which is closely associated with the pathogenesis of AD and vascular dementia. Lowering cholesterol may have a preventive effect on the development of dementia. However, clinical studies have failed to demonstrate an effect of improvement on dementia already established when we try to reduce cholesterol, such as treatment with statins. Therefore, the lipid decrease may be useful to prevent dementia but not to treat it. There have been studies suggesting that high triglycerides levels may impair the long-term memory. The effect of triglycerides may be mediated in part by gastrointestinal hormones such as leptin. Administration of docosahexaenoic acid (DHA), an omega 3 fatty acid, improves cognition in most studies, making it desirable in the diet of individuals with risk factors. (Alzheimer. Real Invest Demenc. 2011;48:33-39)