Micaela Mitolo

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity–or the number of items in a set–which is thought to rely on an “approximate number sense” (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

Relationship between spatial ability, visuospatial working memory and self-assessed spatial orientation ability: a study in older adults

This paper describes some novel spatial tasks and questionnaires designed to assess spatial and orientation abilities. The new tasks and questionnaires were administered to a sample of 90 older adults (41 males, age range 57–90), along with some other tests of spatial ability (Minnesota Paper Form Board, Mental Rotations Test, and Embedded Figures Test) and tests of visuospatial working memory (Corsi’s Block Test and Visual Pattern Test). The internal reliability of the new tasks and questionnaires was analyzed, as well as their relationship with the spatial and working memory tests. The results showed that the new spatial tasks are reliable, correlate with working memory and spatial ability tests and, compared with the latters, show stronger correlations with the self-report questionnaires referring to orientation abilities. A model was also tested (with reference to Allen et al. in Intelligence 22:327–355, 1996) in which the new tasks were assumed to relate to spatial ability and predict orientation abilities as assessed by the self-report measures.

High specificity of MMSE pentagon scoring for diagnosis of prodromal dementia with Lewy bodies.

BACKGROUND Patients with dementia with Lewy bodies (DLB) may display a different cognitive pattern from Alzheimers disease (AD) with more severe impairment performing visuospatial/visuoconstructive tasks. The aim of this study was to investigate whether the analysis of the MMSE pentagon copy could be a useful diagnostic screening tool in prodromal DLB. METHODS Fifty-three patients with Mild Cognitive Impairment (MCI) were followed over 3-years until a diagnosis of DLB (MCI-DLB: n = 30) and AD (MCI-AD: n = 23) were made according to standard criteria. At the first assessment patients underwent a thorough cognitive assessment including the Qualitative Scoring MMSE Pentagon Test (QSPT), the NPI, the UPDRS as well as questionnaires to determine fluctuations and sleep disorders. RESULTS The percentage of subjects who were unable to determine the correct number of angles in the pentagon copy test was 45.1% of MCI-DLB and 8.3% of MCI-AD patients (sensitivity 41.1%; specificity 91%). Attentive/executive functions and visual-spatial abilities were worse in the MCI-DLB group, while episodic memory impairment was greater in MCI-AD. Subtle extrapyramidal signs (63%) and RBD symptoms (56%) were the most frequent clinical features supporting the diagnosis of MCI-DLB. CONCLUSIONS We suggest that a poor performance in determining the number of angles when performing the pentagon copying test, together with the presence of subtle extrapyramidal signs and symptoms of RBD may serve as a predictive tool for early DLB.

Paradigm shift: semantic memory decline as a biomarker of preclinical Alzheimer's disease

Uncovering the presence of Alzheimer’s disease (AD) in routine neurological management of middle-aged/elderly adults, and differentiating its combination of symptoms from those induced by the processes of normal aging, neurovascular disease or psychiatric conditions (e.g., depression), are challenges of primary importance. Usually, it is the onset of behavioral symptoms that encourages patients with AD and caregivers to seek medical attention for the first time. Research evidence, however, shows that the earliest changes triggered by the disease on the biology of the brain occur several decades prior to any behavioral change of clinical relevance [1]. Based on this large preclinicalstage/symptomatic-stage temporal discrepancy, it is of paramount importance to identify biomarkers that are more effective than those currently used in clinical practice. An ideal biomarker should be of as early diagnostic help as possible in the disease-progression timeline, as well as highly sensitive and specific. On this note, the use of cognitive tests is among the most proficient sources of clinical information in the early phases of AD, due to their validity, reliability and simplicity/immediateness. A skillful interpretation of neuropsychological performance may offer an indirect, yet fruitful view of the pathological processes affecting the nervous system, which could be the result of incipient AD. Although episodic memory impairment has been classically recognized as the main symptom of the prodromal AD stage characterized by mild cognitive impairment (MCI) [2], a temporally parallel decline of semantic memory has also been described [3,4]. The basic clinical disadvantage associated with episodic memory is that a qualitatively (but certainly not quantitatively) similar memory decline is also ‘physiologically’ visible in the absence of any pathologies in the general population of elderly adults. In contrast, semantic memory remains fairly stable across the lifespan, and aspects of lexical-semantic abilities even appear to improve with age [5]. Based on this, using the same logic argument that sustains all differential diagnoses, measuring semantic memory can be discriminative in separating healthy and pathological aging. Nevertheless, the most recent criteria for the detection of the earliest clinical manifestation of AD [6,7] persist in highlighting the sole role of measures of episodic retrieval. A major reason behind the choice of episodic memory as the cognitive subdomain ‘of reference’ lies in the fact that prodromal, earlysymptomatic AD (manifesting in the form of MCI) corresponds to the pathophysiological moment in which the neurofibrillary pathology intensifies within the hippocampal complex [8]. This mediotemporal structure sustains the neocortical circuitry responsible for context-associated, episodic memory [9]. Based on this, the theoretical convergence of peptidic accumulation of hypephosphorylated TAU protein within hippocampal cells, Paradigm shift: semantic memory decline as a biomarker of preclinical Alzheimer’s disease

The new Qualitative Scoring MMSE Pentagon Test (QSPT) as a valid screening tool between autopsy-confirmed dementia with lewy bodies and Alzheimer's disease

Visual-constructional apraxia is a prominent feature of dementia with Lewy bodies (DLB) that might help to clinically distinguish it from Alzheimers disease (AD). The main goal of this study was to assess performance on the copy intersecting-pentagon item of the Mini-Mental State Examination with the new Qualitative Scoring method for the Pentagon copy Test (QSPT). In order to determine which aspects of the drawings might differentiate DLB from AD, pentagon drawings of autopsy-verified DLB (n = 16) and AD (n = 15) patients were assessed using the QSPT. The qualitative scoring encompasses the assessment of different parameters of the drawing, such as number of angles, distance/intersection, closure/opening, rotation, and closing-in. The QSPT scores were compared between groups using linear analyses and artificial neural network analyses at four different time points. Linear analyses showed that during the first evaluation, number of angles was the only parameter that showed a significant difference between DLB and AD patients. A gradual decline in other parameters and total pentagon score occurred in both groups during subsequent years, with greater decline for the DLB group. The artificial neural network analyses using auto-contractive maps showed that, with disease progression, DLB became related to relatively lower qualitative pentagon scores, whereas AD became related to relatively higher qualitative scores. These findings suggest that the QSPT might be a sensitive measure of visuo-constructive abilities able to differentiate DLB from AD at disease onset and as the diseases progress, but further studies on larger population are necessary in order to establish its clinical relevance.

Visuospatial Memory and Neuroimaging Correlates in Mild Cognitive Impairment

Spatial abilities decline in normal aging and decrease faster and earlier in Alzheimers disease (AD), but these deficits are under investigated. The main goals of this study were to assess visuospatial memory abilities in mild cognitive impairment (MCI), in order to verify whether these tasks might be valid as the standard cognitive test to differentiate MCI individuals from normal controls and to investigate the brain structural correlates of visuospatial deficits. Twenty MCI patients and fourteen healthy elderly controls underwent an experimental visuospatial battery, which also included self-rating spatial questionnaires, and structural MRI brain imaging. Compared to healthy elderly controls, MCI patients scored significantly worse in almost all visuospatial tasks. ROC analysis showed that visuospatial tasks had an elevated discriminant power between groups (AUC >0.90). Voxel-based morphometry analysis, compared to controls, disclosed a higher level of atrophy in frontal and medio-temporal regions and a different pattern of correlation between grey matter values and visuospatial performance, with wider distributed areas of the occipital and middle temporal cortex in the map and route learning. This study indicates that visuospatial memory tests are valid tools in completing the diagnostic evaluation of MCI.

Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimers disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinsons Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagons number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagons number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

White Matter Hyperintensity Load Modulates Brain Morphometry and Brain Connectivity in Healthy Adults: A Neuroplastic Mechanism?

White matter hyperintensities (WMHs) are acquired lesions that accumulate and disrupt neuron-to-neuron connectivity. We tested the associations between WMH load and (1) regional grey matter volumes and (2) functional connectivity of resting-state networks, in a sample of 51 healthy adults. Specifically, we focused on the positive associations (more damage, more volume/connectivity) to investigate a potential route of adaptive plasticity. WMHs were quantified with an automated procedure. Voxel-based morphometry was carried out to model grey matter. An independent component analysis was run to extract the anterior and posterior default-mode network, the salience network, the left and right frontoparietal networks, and the visual network. Each model was corrected for age, global levels of atrophy, and indices of brain and cognitive reserve. Positive associations were found with morphometry and functional connectivity of the anterior default-mode network and salience network. Within the anterior default-mode network, an association was found in the left mediotemporal-limbic complex. Within the salience network, an association was found in the right parietal cortex. The findings support the suggestion that, even in the absence of overt disease, the brain actuates a compensatory (neuroplastic) response to the accumulation of WMH, leading to increases in regional grey matter and modified functional connectivity.

How to enhance route learning and visuo-spatial working memory in aging: a training for residential care home residents

ABSTRACT Objectives: This study aimed to assess the efficacy of a route-learning training in a group of older adults living in a residential care home. We verified the presence of training-specific effects in tasks similar to those trained – route-learning tasks – as well as transfer effects on related cognitive processes – visuo-spatial short-term memory (VSSTM; Corsi Blocks Test (CBT), forward version), visuo-spatial working memory (VSWM; CBT, backward version; Pathway Span Tasks; Jigsaw Puzzle Test) – and in self-report measures. The maintenance of training benefits was examined after 3 months. Method: Thirty 70–90-year-old residential care home residents were randomly assigned to the route-learning training group or to an active control group (involved in non-visuo-spatial activities). Results: The trained group performed better than the control group in the route-learning tasks, retaining this benefit 3 months later. Immediate transfer effects were also seen in visuo-spatial span tasks (i.e., CBT forward and backward version and Pathway Span Task); these benefits had been substantially maintained at the 3-month follow-up. Conclusion: These findings suggest that a training on route learning is a promising approach to sustain older adults’ environmental learning and some related abilities (e.g., VSSTM and VSWM), even in residential care home residents.

Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease

There is emerging evidence suggesting that Alzheimers disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s−1 between the two cases.