Outcomes and safety of endovascular treatment from 6 to 24 hours in patients with a pre-stroke moderate disability (mRS 3): a multicenter retrospective study.

BACKGROUND: Approximately 30% of patients presenting with acute ischemic stroke (AIS) due to large vessel occlusion have pre-stroke modified Rankin Scale (mRS) scores ≥2. We aimed to investigate the safety and outcomes of endovascular treatment (EVT) in patients with AIS with moderate pre-stroke disability (mRS score 3) in an extended time frame (ie, 6-24 hours from the last time known well). METHODS: Data were collected from five centers in Europe and the USA from January 2018 to January 2023 and included 180 patients who underwent EVT in an extended time frame. Patients were divided into two groups of 90 each (Group 1: pre-mRS 0-2; Group 2: pre-mRS 3; 71% women, mean age 80.3±11.9 years). Primary outcomes were: (1) 3-month good clinical outcome (Group 1: mRS 0-2, Group 2: mRS 0-3) and ΔmRS; (2) any hemorrhagic transformation (HT); and (3) symptomatic HT. Secondary outcomes were successful and complete recanalization after EVT and 3-month mortality. RESULTS: No between-group differences were found in the 3-month good clinical outcome (26.6% vs 25.5%, P=0.974), any HT (26.6% vs 22%, P=0.733), and symptomatic HT (8.9 vs 4.4%, P=0.232). Unexpectedly, ΔmRS was significantly smaller in Group 2 compared with Group 1 (1.64±1.61 vs 2.97±1.69, P<0.001). No between-group differences were found in secondary outcomes. CONCLUSION: Patients with pre-stroke mRS 3 are likely to have similar outcomes after EVT in the extended time frame to those with pre-stroke mRS 0-2, with no difference in safety.

CT Perfusion as a Predictor of the Final Infarct Volume in Patients with Tandem Occlusion.

BACKGROUND: CT perfusion (CTP) is used in patients with anterior circulation acute ischemic stroke (AIS) for predicting the final infarct volume (FIV). Tandem occlusion (TO), involving both intracranial large vessels and the ipsilateral cervical internal carotid artery could generate hemodynamic changes altering perfusion parameters. Our aim is to evaluate the accuracy of CTP in the prediction of the FIV in TOs. METHODS: consecutive patients with AIS due to middle cerebral artery occlusion, referred to a tertiary stroke center between March 2019 and January 2021, with an automated CTP and successful recanalization (mTICI = 2b - 3) after endovascular treatment were retrospectively included in the tandem group (TG) or in the control group (CG). Patients with parenchymal hematoma type 2, according to ECASS II classification of hemorrhagic transformations, were excluded in a secondary analysis. Demographic, clinical, radiological, time intervals, safety, and outcome measures were collected. RESULTS: among 319 patients analyzed, a comparison between the TG (N = 22) and CG (n = 37) revealed similar cerebral blood flow (CBF) > 30% (29.50 ± 32.33 vs. 15.76 ± 20.93 p = 0.18) and FIV (54.67 ± 65.73 vs. 55.14 ± 64.64 p = 0.875). Predicted ischemic core (PIC) and FIV correlated in both TG (tau = 0.761, p < 0.001) and CG (tau = 0.315, p = 0.029). The Bland-Altmann plot showed agreement between PIC and FIV for both groups, mainly in the secondary analysis. CONCLUSION: automated CTP could represent a good predictor of FIV in patients with AIS due to TO.

The impact of aging on human brain network target controllability.

Understanding how few distributed areas can steer large-scale brain activity is a fundamental question that has practical implications, which range from inducing specific patterns of behavior to counteracting disease. Recent endeavors based on network controllability provided fresh insights into the potential ability of single regions to influence whole brain dynamics through the underlying structural connectome. However, controlling the entire brain activity is often unfeasible and might not always be necessary. The question whether single areas can control specific target subsystems remains crucial, albeit still poorly explored. Furthermore, the structure of the brain network exhibits progressive changes across the lifespan, but little is known about the possible consequences in the controllability properties. To address these questions, we adopted a novel target controllability approach that quantifies the centrality of brain nodes in controlling specific target anatomo-functional systems. We then studied such target control centrality in human connectomes obtained from healthy individuals aged from 5 to 85. Main results showed that the sensorimotor system has a high influencing capacity, but it is difficult for other areas to influence it. Furthermore, we reported that target control centrality varies with age and that temporal-parietal regions, whose cortical thinning is crucial in dementia-related diseases, exhibit lower values in older people. By simulating targeted attacks, such as those occurring in focal stroke, we showed that the ipsilesional hemisphere is the most affected one regardless of the damaged area. Notably, such degradation in target control centrality was more evident in younger people, thus supporting early-vulnerability hypotheses after stroke.

The Destiny of Multiple Domain Amnesic Mild Cognitive Impairment: Effect of Alternative Neuropsychological Definitions and Their Adjunctive Role in Respect of Memory Impairment.

OBJECTIVE: Mild cognitive impairment is the main risk factor of dementia. Previous evidence has claimed that subjects with memory disturbances associated with impairment of other cognitive domains (multiple domain amnesic MCI) are at the highest risk of developing dementia. To date, a shared definition of amnesic MCI multiple domain (aMCI-MD) is still lacking. METHOD: 163 subjects with aMCI were enrolled and followed-up for 2 years. They underwent a baseline comprehensive neuropsychological battery. The cut-off point for each test was set at 1, 1.5, and 2 SD below the mean obtained in normative studies; aMCI-MD was defined as the occurrence of abnormal scores on at least one, two, or three tests not assessing memory. The Episodic Memory Score (EMS), that measures the severity of memory impairment, was determined. Logistic regressionand Cox's proportional hazard risk models were carried out. The adjunctive effect of the definitions of aMCI-MD on the severity of memory impairment was assessed. RESULTS: Fifty-four subjects progressed to dementia. Only restrictive definitions of aMCI-MD (at least three tests below 1.5 SD; at least two tests below 2 SD) predicted conversion to dementia in both logistic regression and survival analysis. None of the conditions showed a significant adjunctive effect on the EMS. CONCLUSIONS: The predictive effect of impairment in tests assessing cognitive domains other than memory depends on its psychometric definition. The use of a restrictive definition would be of some usefulness, but the adjunctive effect of such a definition on an integrated analysis of memory impairment may be questionable.

Learning Processes and Brain Connectivity in A Cognitive-Motor Task in Neurodegeneration: Evidence from EEG Network Analysis.

Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions.

Sustainable method for Alzheimer dementia prediction in mild cognitive impairment: Electroencephalographic connectivity and graph theory combined with apolipoprotein E.

OBJECTIVE: Mild cognitive impairment (MCI) is a condition intermediate between physiological brain aging and dementia. Amnesic-MCI (aMCI) subjects progress to dementia (typically to Alzheimer-Dementia = AD) at an annual rate which is 20 times higher than that of cognitively intact elderly. The present study aims to investigate whether EEG network Small World properties (SW) combined with Apo-E genotyping, could reliably discriminate aMCI subjects who will convert to AD after approximately a year. METHODS: 145 aMCI subjects were divided into two sub-groups and, according to the clinical follow-up, were classified as Converted to AD (C-MCI, 71) or Stable (S-MCI, 74). RESULTS: Results showed significant differences in SW in delta, alpha1, alpha2, beta2, gamma bands, with C-MCI in the baseline similar to AD. Receiver Operating Characteristic(ROC) curve, based on a first-order polynomial regression of SW, showed 57% sensitivity, 66% specificity and 61% accuracy(area under the curve: AUC=0.64). In 97 out of 145 MCI, Apo-E allele testing was also available. Combining this genetic risk factor with Small Word EEG, results showed: 96.7% sensitivity, 86% specificity and 91.7% accuracy(AUC=0.97). Moreover, using only the Small World values in these 97 subjects, the ROC showed an AUC of 0.63; the resulting classifier presented 50% sensitivity, 69% specificity and 59.6% accuracy. When different types of EEG analysis (power density spectrum) were tested, the accuracy levels were lower (68.86%). INTERPRETATION: Concluding, this innovative EEG analysis, in combination with a genetic test (both low-cost and widely available), could evaluate on an individual basis with great precision the risk of MCI progression. This evaluation could then be used to screen large populations and quickly identify aMCI in a prodromal stage of dementia. Ann Neurol 2018 Ann Neurol 2018;84:302-314.

Predicting progression of amnesic MCI: The integration of episodic memory impairment with perfusion SPECT.

The present study aimed at assessing if the ability to predict progression from amnesic Mild Cognitive Impairment (aMCI) to dementia is improved by considering the presence at the baseline of Single Photon Emission Computed Tomography (SPECT) perfusion abnormalities in addition to a defect of long term memory. The Episodic Memory Score (EMS), a global index which integrates results obtained in subtests of the Rey's Verbal Learning Test and the Rey-Osterrieth Figure recall, were taken into account to evaluate defects of long term memory. The study sample consisted of 42 subjects affected by aMCI, who were followed-up during a two-year period. At the final follow-up 15 subjects progressed to AD. The EMS predicted progression from aMCI to dementia with a high level of sensitivity and a lower level of specificity, but the association of neuropsychological (EMS) and SPECT data (hypoperfusion in the Posterior Cingulate Cortex) increased the accuracy in predicting conversion from aMCI to AD. The association of results obtained by aMCI patients on memory tests and perfusion SPECT may improve the accuracy in detecting subjects who will progress to dementia. The use of currently available and low-cost investigations could be advantageous in terms of public health policies.

Accelerated Long-Term Forgetting Limited to the Recollection Component of Recognition Memory in a Temporal Lobe Epileptic Patient.

Accelerated long-term forgetting (ALF) is a frequent finding in patients with temporal lobe epilepsy (TLE). Here we report the case of a TLE patient who complained of marked difficulties in remembering personal events and information even though repeated neuropsychological assessments had failed to detect any deficit on common laboratory memory tests. The patient underwent an experimental investigation that involved estimating recollection and familiarity processes in the performance on verbal and visual recognition tests, over intervals ranging from 10 minutes to 7 days. Results showed accelerated forgetting confined to the recollection component only, which was particularly evident in the verbal test.

In Search of Sleep Biomarkers of Alzheimer's Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls.

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer's disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration.

The Fall of Sleep K-Complex in Alzheimer Disease.

Although a slowing of electroencephalographic (EEG) activity during wakefulness and -to some extent- sleep of Alzheimer disease (AD) patients (i.e., increased slow-frequency activity) was documented, recent findings in healthy elderly show a decreased 0.6-1 Hz slow wave activity (SWA) during NREM, which was associated to ß-amyloid deposition and impaired hippocampal memory consolidation. We hypothesize that the apparent contradiction may be explained by the partial overlap between 0.6-1 Hz EEG activity and K-Complex (KC). According to this view, we studied both frontal KCs and SWA in 20 AD patients and 20 healthy age-matched controls (HC) during nightly sleep, under the hypothesis that KCs better discriminate patients from healthy elderly than ≤1 Hz SWA. A drastic decrease of KC density during stage 2 NREM was found in AD compared to HC. Patients show more than 40% reduction of the KC density, allowing a correct classification of 80%. On the other hand, ≤1 Hz SWA of AD patients is slightly (not significantly) higher in most cortical areas compared to HC. Although no significant changes of ≤1 Hz SWA are detectable over frontal areas in AD, KC density decreases over the same location, and its decrease is related to the cognitive decline.

Small-World Characteristics of Cortical Connectivity Changes in Acute Stroke.

Background After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. Recently, complexity of brain connectivity has been described using graph theory, a mathematical approach that depicts important properties of complex systems by quantifying topologies of network representations. Functional and dynamic changes of brain connectivity can be reliably analyzed via electroencephalography (EEG) recordings even when they are not yet reflected in structural changes of connections. Objective We tested whether and how ischemic stroke in the acute stage may determine changes in small-worldness of cortical networks as measured by cortical sources of EEG. Methods Graph characteristics of EEG of 30 consecutive stroke patients in acute stage (no more than 5 days after the event) were examined. Connectivity analysis was performed using eLORETA in both hemispheres. Results Network rearrangements were mainly detected in delta, theta, and alpha bands when patients were compared with healthy subjects. In delta and alpha bands similar findings were observed in both hemispheres regardless of the side of ischemic lesion: bilaterally decreased small-worldness in the delta band and bilaterally increased small-worldness in the alpha2 band. In the theta band, bilaterally decreased small-worldness was observed only in patients with stroke in the left hemisphere. Conclusions After an acute stroke, brain cortex rearranges its network connections diffusely, in a frequency-dependent modality probably in order to face the new anatomical and functional frame.

Are Raw Scores on Memory Tests Better than Age- and Education- Adjusted Scores for Predicting Progression from Amnesic Mild Cognitive Impairment to Alzheimer Disease ?

In this prospective longitudinal study, conducted in a large sample of amnestic MCI patients over a three-year period, we investigated the recently advanced proposal that unadjusted test scores obtained at baseline on long-term memory tests are more reliable than age- and education-corrected scores in predicting progression from aMCI to AD. Our experimental sample consisted of 270 aMCI patients who underwent extensive neurological and neuropsychological examinations both at baseline and at the follow-up, conducted at least 3 years later. At the follow-up 80 patients had converted to overt dementia. The predictive capacity of raw, age-corrected, education-corrected and fully corrected scores on RAVLT immediate and delayed recall was compared by examining the area under the ROC curves (AUCs) of all of these scores to assess which (raw or corrected) scores achieves the better reliability in predicting conversion to dementia. The condition (aMCI stable vs converted) was analyzed to assess the odds ratios resulting from a logistic regression on the corrected and uncorrected scores of RAVLT immediate and delayed recall. Even if both in immediate and in delayed recall the ROCs of 'raw scores' were generally higher than the other ROCs on corrected scores, these differences did not reach the level of statistical significance, failing to support the claim that unadjusted test scores are superior to age- and education-corrected scores in predicting progression from aMCI to AD.

Usefulness of an Integrated Analysis of Different Memory Tasks to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease: The Episodic Memory Score (EMS).

Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer's disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.

Classification of Healthy Subjects and Alzheimer's Disease Patients with Dementia from Cortical Sources of Resting State EEG Rhythms: A Study Using Artificial Neural Networks.

Previous evidence showed a 75.5% best accuracy in the classification of 120 Alzheimer's disease (AD) patients with dementia and 100 matched normal elderly (Nold) subjects based on cortical source current density and linear lagged connectivity estimated by eLORETA freeware from resting state eyes-closed electroencephalographic (rsEEG) rhythms (Babiloni et al., 2016a). Specifically, that accuracy was reached using the ratio between occipital delta and alpha1 current density for a linear univariate classifier (receiver operating characteristic curves). Here we tested an innovative approach based on an artificial neural network (ANN) classifier from the same database of rsEEG markers. Frequency bands of interest were delta (2-4 Hz), theta (4-8 Hz Hz), alpha1 (8-10.5 Hz), and alpha2 (10.5-13 Hz). ANN classification showed an accuracy of 77% using the most 4 discriminative rsEEG markers of source current density (parietal theta/alpha 1, temporal theta/alpha 1, occipital theta/alpha 1, and occipital delta/alpha 1). It also showed an accuracy of 72% using the most 4 discriminative rsEEG markers of source lagged linear connectivity (inter-hemispherical occipital delta/alpha 2, intra-hemispherical right parietal-limbic alpha 1, intra-hemispherical left occipital-temporal theta/alpha 1, intra-hemispherical right occipital-temporal theta/alpha 1). With these 8 markers combined, an accuracy of at least 76% was reached. Interestingly, this accuracy based on 8 (linear) rsEEG markers as inputs to ANN was similar to that obtained with a single rsEEG marker (Babiloni et al., 2016a), thus unveiling their information redundancy for classification purposes. In future AD studies, inputs to ANNs should include other classes of independent linear (i.e., directed transfer function) and non-linear (i.e., entropy) rsEEG markers to improve the classification.

Thalamic Amnesia Mimicking Transient Global Amnesia.

INTRODUCTION: Transient global amnesia is a benign syndrome and one of the most frequent discharges from the emergency department that can hardly be distinguished from other mimicking diseases. No consensus in the evaluation of transient global amnesia has yet been found in the emergency setting. CASE REPORT: We describe a 69-year-old woman who presented to our emergency department with an abrupt onset of anterograde amnesia, preceded by a similar amnesic episode misinterpreted as transient global amnesia. Neuroradiologic, neuropsychological, and neurophysiological evaluations supported the diagnosis of vascular thalamic amnesia. CONCLUSIONS: We report a patient who clinically fulfilled transient global amnesia's criteria and in whom nevertheless was disclosed a thalamic ischemic lesion on neuroimaging.This case report highlights the importance of performing neuroradiologic screening in the emergency department even when clinical history and physical findings are highly suggestive for transient global amnesia.

Does semantic memory impairment in amnestic MCI with hippocampal atrophy conform to a distinctive pattern of progression?

Subjects with Mild Cognitive Impairment (MCI) are normally classified according to the presence of episodic memory deficits associated or not to disturbances of other cognitive domains. The present study had two aims: to identify discrete subtypes of amnestic MCI (a-MCI) with hippocampal atrophy; and to assess if the identified subtypes show different rates of progression to dementia. Sixty-seven a-MCI subjects were enrolled, all showing significant hippocampal atrophy on MRI. The subjects underwent at baseline and at follow-up a comprehensive neuropsychological examination, and were followed-up for five years to detect the conversion to dementia. An exploratory factor analysis on neuropsychological performances at baseline identified three main factors that were subsequently used to perform a k-means cluster analysis. Three cluster of a-MCI subjects were identified: "pure amnestic" (N=29), "multiple domain"(N=16), and "amnestic/semantic"(N=22). The successive discriminant functions were able to correctly classify 88% of the subjects. During the follow-up, 33 subjects converted to dementia (49.2%), 14 "pure amnestic" (48.3%), 11 "multiple domain" (68.5%) and 8 "amnestic/semantic" (36.4%; log-rank: p=0.016); median survival was respectively 36, 22, and 39 months. On Cox proportional hazard model, baseline MMSE (HR=0,709; p=0.006), education (HR=1,115; p=0.011) and belonging to the "multiple domain" subgroup (HR=2,706; p=0.013) were significantly associated to higher rate of conversion to dementia. Our findings confirm the tendency to worst outcome of subjects with multiple domain MCI, and show that the association of episodic and semantic memory deficits, without other cognitive disturbances, could identify a specific cognitive pattern associated to slower cognitive decline, as previously reported in Alzheimer's Disease.

Prestimulus interhemispheric coupling of brain rhythms predicts cognitive-motor performance in healthy humans.

Physiological and neuroimaging studies suggest that human actions are characterized by time-varying engagement of functional distributed networks within the brain. In this study, we investigated whether specific prestimulus interhemispheric connectivity, as a measure of synchronized network between the two hemispheres, could lead to a better performance (as revealed by RT) in a simple visuomotor task. Eighteen healthy adults underwent EEG recording during a visual go/no-go task. In the go/no-go task, a central fixation stimulus was followed by a green (50% of probability) or red visual stimulus. Participants had to press the mouse button after the green stimuli (go trials). Interhemispheric coupling was evaluated by the spectral coherence among all the electrodes covering one hemisphere and matched with those on the other. The frequency bands of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The task-related results showed that interhemispheric connectivity decreased in delta and increased in alpha band. Furthermore, we observed positive delta and negative alpha correlations with the RT; namely, the faster the RT, the lower delta and the higher alpha connection between the two hemispheres. These results suggested that the best performance is anticipated by the better functional coupling of cortical circuits involved during the processing of the sensorimotor information, occurring between the two hemispheres pending cognitive go/no-go task.

Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains.

Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid ß deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.