A deep learning model for generating [18F]FDG PET Images from early-phase [18F]Florbetapir and [18F]Flutemetamol PET images.

INTRODUCTION: Amyloid-ß (Aß) plaques is a significant hallmark of Alzheimer's disease (AD), detectable via amyloid-PET imaging. The Fluorine-18-Fluorodeoxyglucose ([18F]FDG) PET scan tracks cerebral glucose metabolism, correlated with synaptic dysfunction and disease progression and is complementary for AD diagnosis. Dual-scan acquisitions of amyloid PET allows the possibility to use early-phase amyloid-PET as a biomarker for neurodegeneration, proven to have a good correlation to [18F]FDG PET. The aim of this study was to evaluate the added value of synthesizing the later from the former through deep learning (DL), aiming at reducing the number of PET scans, radiation dose, and discomfort to patients. METHODS: A total of 166 subjects including cognitively unimpaired individuals (N = 72), subjects with mild cognitive impairment (N = 73) and dementia (N = 21) were included in this study. All underwent T1-weighted MRI, dual-phase amyloid PET scans using either Fluorine-18 Florbetapir ([18F]FBP) or Fluorine-18 Flutemetamol ([18F]FMM), and an [18F]FDG PET scan. Two transformer-based DL models called SwinUNETR were trained separately to synthesize the [18F]FDG from early phase [18F]FBP and [18F]FMM (eFBP/eFMM). A clinical similarity score (1: no similarity to 3: similar) was assessed to compare the imaging information obtained by synthesized [18F]FDG as well as eFBP/eFMM to actual [18F]FDG. Quantitative evaluations include region wise correlation and single-subject voxel-wise analyses in comparison with a reference [18F]FDG PET healthy control database. Dice coefficients were calculated to quantify the whole-brain spatial overlap between hypometabolic ([18F]FDG PET) and hypoperfused (eFBP/eFMM) binary maps at the single-subject level as well as between [18F]FDG PET and synthetic [18F]FDG PET hypometabolic binary maps. RESULTS: The clinical evaluation showed that, in comparison to eFBP/eFMM (average of clinical similarity score (CSS) = 1.53), the synthetic [18F]FDG images are quite similar to the actual [18F]FDG images (average of CSS = 2.7) in terms of preserving clinically relevant uptake patterns. The single-subject voxel-wise analyses showed that at the group level, the Dice scores improved by around 13% and 5% when using the DL approach for eFBP and eFMM, respectively. The correlation analysis results indicated a relatively strong correlation between eFBP/eFMM and [18F]FDG (eFBP: slope = 0.77, R2 = 0.61, P-value < 0.0001); eFMM: slope = 0.77, R2 = 0.61, P-value < 0.0001). This correlation improved for synthetic [18F]FDG (synthetic [18F]FDG generated from eFBP (slope = 1.00, R2 = 0.68, P-value < 0.0001), eFMM (slope = 0.93, R2 = 0.72, P-value < 0.0001)). CONCLUSION: We proposed a DL model for generating the [18F]FDG from eFBP/eFMM PET images. This method may be used as an alternative for multiple radiotracer scanning in research and clinical settings allowing to adopt the currently validated [18F]FDG PET normal reference databases for data analysis.

Alzheimer resemblance atrophy index, BrainAGE, and normal pressure hydrocephalus score in the prediction of subtle cognitive decline: added value compared to existing MR imaging markers.

OBJECTIVES: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls. METHODS: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers. RESULTS: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%. CONCLUSIONS: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs. KEY POINTS: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects.

BACKGROUND: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. METHODS: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. RESULTS: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. CONCLUSION: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls.

BACKGROUND: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals. METHODS: 62 elderly individuals (41 females), including 41 controls (35 females) and 21 middle cognitive impairment subjects (6 females), underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON) with preserved cognition and deteriorating controls (dCON) with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT) for the 2-back condition and general linear model (GLM) for the fMRI sequence. RESULTS: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN) and of the Default Mode Network (DFM) were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON. CONCLUSION: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.

Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline.

PURPOSE: Recent evidence indicates that caffeine may have a beneficial effect on cognitive decline and dementia. The current investigation assessed the effect of acute caffeine administration on working memory during the earliest stage of cognitive decline in elderly participants. METHODS: The study includes consecutive 45 elderly controls and 18 individuals with mild cognitive impairment (MCI, 71.6 ± 4.7 years, 7 females). During neuropsychological follow-up at 18 months, 24 controls remained stable (sCON, 70.0 ± 4.3 years, 11 women), while the remaining 21 showed subtle cognitive deterioration (dCON, 73.4 ± 5.9 years, 14 women). All participants underwent an established 2-back working task in a crossover design of 200 mg caffeine versus placebo. Data analysis included task-related general linear model and functional connectivity tensorial independent component analysis. RESULTS: Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p < 0.05). The dCON group had a less pronounced effect of acute caffeine administration essentially restricted to the right hemisphere (p < 0.05 corrected) and reduced default mode network (DMN) deactivation compared to sCON (p < 0.01 corrected). CONCLUSION: dCON cases are characterized by decreased sensitivity to caffeine effects on brain activation and DMN deactivation. These complex fMRI patterns possibly reflect the instable status of these cases with intact behavioral performances despite already existing functional alterations in neocortical circuits.

Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals.

PURPOSE: To explore whether arterial spin labeling (ASL) imaging in cognitively intact elderly individuals may be used to predict subsequent early neuropsychological decline. MATERIALS AND METHODS: The local ethics committee approved this prospective study, and written informed consent was obtained from all participants. A total of 148 consecutive control subjects were included, 75 of whom had stable cognitive function (sCON) (mean age, 75.9 years ± 3.4 [standard deviation]; 43 female) and 73 of whom had deteriorated cognitive function (dCON) at 18-month clinical follow-up (mean age, 76.8 years ± 4.1; 44 female). An additional 65 patients with mild cognitive impairment (MCI) (mean age, 76.2 years ± 6.1; 25 female) were also included. Two-dimensional pulsed ASL was performed at the baseline visit. Statistical analysis included whole-brain voxelwise analysis of the ASL relative cerebral blood flow (CBF) data, receiver operating characteristic (ROC) curve analysis of the posterior cingulate cortex (PCC), and voxel-based morphometry analysis of gray matter. RESULTS: The voxelwise comparison of ASL revealed decreased relative CBF in the dCON group compared with that in the sCON group and slightly more pronounced relative CBF in the MCI group compared with that in the sCON group, most notably in the PCC (P < .05 corrected). Comparison of the dCON group with the MCI group revealed no significant differences. ROC analysis of relative CBF in the PCC enabled discrimination of dCON (P < .001; area under the ROC curve, 0.66). There was no confounding focal gray matter atrophy. CONCLUSION: Reduced ASL in the PCC at baseline is associated with the development of subsequent subtle neuropsychological deficits in healthy elderly control subjects. At a group level, ASL patterns in subjects with dCON are similar to those in patients with MCI at baseline, indicating that these subjects may initially maintain their cognitive status via mobilization of their neurocognitive reserve at baseline; however, they are likely to develop subsequent subtle cognitive deficits.

Wearing a KN95/FFP2 facemask has no measureable effect on functional activity in a challenging working memory n-back task.

Introduction: Wide use of facemasks is one of the many consequences of the COVID-19 pandemic. Methods: We used an established working memory n-back task in functional magnetic resonance imaging (fMRI) to explore whether wearing a KN95/FFP2 facemask affects overall performance and brain activation patterns. We provide here a prospective crossover design 3 T fMRI study with/without wearing a tight FFP2/KN95 facemask, including 24 community-dwelling male healthy control participants (mean age ± SD = 37.6 ± 12.7 years) performing a 2-back task. Data analysis was performed using the FSL toolbox, performing both task-related and functional connectivity independent component analyses. Results: Wearing an FFP2/KN95 facemask did not impact behavioral measures of the 2-back task (response time and number of errors). The 2-back task resulted in typical activations in working-memory related areas in both MASK and NOMASK conditions. There were no statistically significant differences in MASK versus NOMASK while performing the 2-back task in both task-related and functional connectivity fMRI analyses. Conclusion: The effect of wearing a tight FFP2/KN95 facemasks did not significantly affect working memory performance and brain activation patterns of functional connectivity.

Age-associated modulations of cerebral oscillatory patterns related to attention control.

Visual attention depends on bottom-up sensory activation and top-down attentional guidance. Although aging is known to affect sensory processing, its impact on the top-down control of attention remains a matter of debate. We investigated age-related modulations of brain oscillatory activity during visual attention using a variant of the attention network test (ANT) in 20 young and 28 elderly adults. We examined the EEG oscillatory responses to warning and target signals, and explored the correlates of temporal and spatial orienting as well as conflict resolution at target presentation. Time-frequency analysis was performed between 4 and 30 Hz, and the relationship between behavioral and brain oscillatory responses was analyzed. Whereas temporal cueing and conflict had similar reaction time effects in both age groups, spatial cueing was more beneficial to older than younger subjects. In the absence of cue, posterior alpha activation was drastically reduced in older adults, pointing to an age-related decline in anticipatory attention. Following both cues and targets, older adults displayed pronounced motor-related activation in the low beta frequency range at the expense of attention-related posterior alpha activation prominent in younger adults. These findings support the recruitment of alternative motor-related circuits in the elderly, in line with the dedifferentiation hypothesis. Furthermore, older adults showed reduced midparietal alpha inhibition induced by temporal orienting as well as decreased posterior alpha activation associated with both spatial orienting and conflict resolution. Altogether, the results are consistent with an overall reduction of task-related alpha activity in the elderly, and provide functional evidence that younger and older adults engage distinct brain circuits at different oscillatory frequencies during attentional functions.

Neuroimaging of dementia in 2013: what radiologists need to know.

The structural and functional neuroimaging of dementia have substantially evolved over the last few years. The most common forms of dementia, Alzheimer disease (AD), Lewy body dementia (LBD) and fronto-temporal lobar degeneration (FTLD), have distinct patterns of cortical atrophy and hypometabolism that evolve over time, as reviewed in the first part of this article. The second part discusses unspecific white matter alterations on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images as well as cerebral microbleeds, which often occur during normal aging and may affect cognition. The third part summarises molecular neuroimaging biomarkers recently developed to visualise amyloid deposits, tau protein deposits and neurotransmitter systems. The fourth section reviews the utility of advanced image analysis techniques as predictive biomarkers of cognitive decline in individuals with early symptoms compatible with mild cognitive impairment (MCI). As only about half of MCI cases will progress to clinically overt dementia, whereas the other half remain stable or might even improve, the discrimination of stable versus progressive MCI is of paramount importance for both individual patient treatment and patient selection for clinical trials. The fifth and final part discusses the inter-individual variation in the neurocognitive reserve, which is a potential constraint for all proposed methods.

Attention-related potentials allow for a highly accurate discrimination of mild cognitive impairment subtypes.

The three most frequent forms of mild cognitive impairment (MCI) are single-domain amnestic MCI (sd-aMCI), single-domain dysexecutive MCI (sd-dMCI) and multiple-domain amnestic MCI (md-aMCI). Brain imaging differences among single domain subgroups of MCI were recently reported supporting the idea that electroencephalography (EEG) functional hallmarks can be used to differentiate these subgroups. We performed event-related potential (ERP) measures and independent component analysis in 18 sd-aMCI, 13 sd-dMCI and 35 md-aMCI cases during the successful performance of the Attentional Network Test. Sensitivity and specificity analyses of ERP for the discrimination of MCI subgroups were also made. In center-cue and spatial-cue warning stimuli, contingent negative variation (CNV) was elicited in all MCI subgroups. Two independent components (ICA1 and 2) were superimposed in the time range on the CNV. The ICA2 was strongly reduced in sd-dMCI compared to sd-aMCI and md-aMCI (4.3 vs. 7.5% and 10.9% of the CNV component). The parietal P300 ERP latency increased significantly in sd-dMCI compared to md-aMCI and sd-aMCI for both congruent and incongruent conditions. This latency for incongruent targets allowed for a highly accurate separation of sd-dMCI from both sd-aMCI and md-aMCI with correct classification rates of 90 and 81%, respectively. This EEG parameter alone performed much better than neuropsychological testing in distinguishing sd-dMCI from md-aMCI. Our data reveal qualitative changes in the composition of the neural generators of CNV in sd-dMCI. In addition, they document an increased latency of the executive P300 component that may represent a highly accurate hallmark for the discrimination of this MCI subgroup in routine clinical settings.

Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus.

The occurrence of significant Alzheimer's disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH.

Mentalizing and self-other distinction in visual perspective taking: the analysis of temporal neural processing using high-density EEG.

This high density EEG report dissects the neural processing in the visual perspective taking using four experimental comparisons (Arrow, Avatar and Self, Other). Early activation differences occurred between the Avatar and the Arrow condition in primary visual pathways concomitantly with alpha and beta phase locked responses predominant in the Avatar condition. In later time points, brain activation was stronger for the Avatar condition in paracentral lobule of frontal lobe. When taking the other's perspective, there was an increased recruitment of generators in the occipital and temporal lobes and later on in mentalizing and salience networks bilaterally before spreading to right frontal lobe subdivisions. Microstate analysis further supported late recruitment of the medial frontal gyrus and precentral lobule in this condition. Other perspective for the Avatar only showed a strong beta response located first in left occipito-temporal and right parietal areas, and later on in frontal lobes. Our EEG data support distinct brain processes for the Avatar condition with an increased recruitment of brain generators that progresses from primary visual areas to the anterior brain. Taking the other's perspective needs an early recruitment of neural processors in posterior areas involved in theory of mind with later involvement of additional frontal generators.

Seeing in my way or your way: impact of intelligence, attention, and empathy on brain reactivity.

Previous studies showed that neurotypical adults are able to engage in unconscious analyses of others' mental states in the context of automatic perspective taking and experience systematic difficulties when judging the conflicts between their own (Self) and another's (Other) perspective. Several functional MRI (fMRI) studies reported widespread activation of mentalizing, salience, and executive networks when adopting the Other compared to Self perspective. This study aims to explore whether cognitive and emotional parameters impact on brain reactivity in dot perspective task (dPT). We provide here an fMRI analysis based on individual z-scores in eighty-two healthy adults who underwent the Samson's dPT after detailed assessment of fluid intelligence, attention, levels of alexithymia and social cognition abilities. Univariate regression models were used to explore the association between brain activation patterns and psychological variables. There was a strong positive association between Wechsler Adult Intelligence Scale (WAIS) and fMRI z-scores in Self perspective. When the Other perspective is taken, Continuous Performance Test (CPT)-II parameters were negatively associated with fMRI z-scores. Individuals with higher Toronto Alexithymia scale (TAS) score and lower scores in mini-Social cognition and Emotional Assessment (SEA) displayed significantly higher egocentric interference-related fMRI z-scores. Our data demonstrate that brain activation when focusing on our own perspective depends on the levels of fluid intelligence. Decreased attentional recruitment and decreased inhibitory control affects the brain efforts to adopt the Other perspective. Egocentric interference-associated brain fMRI activation was less marked in cases with better empathy abilities but the opposite was true for persons who experience increased difficulties in the recognition of emotions.

Patterns of multiple brain network activation in dot perspective task.

In this functional MRI (fMRI) study on 82 healthy adults using the dot perspective task, inconsistency of perspectives was associated with a significant increase of the mean reaction time and number of errors both in Self and Other conditions. Unlike the Arrow (non-mentalizing), the Avatar (mentalizing) paradigm was characterized by the recruitment of parts of the mentalizing and salience networks. These data provide experimental evidence supporting the fMRI distinction between mentalizing and non-mentalizing stimuli. A widespread activation of classical theory of mind (ToM) areas but also of salience network and decision making areas was observed in the Other compared to Self-conditions. Compared to Self-Consistent, Self-Inconsistent trials were related to increased activation in the lateral occipital cortex, right supramarginal and angular gyrus as well as inferior, superior and middle frontal gyri. Compared to the Other-Consistent, Other-Inconsistent trials yielded strong activation in the lateral occipital cortex, precuneus and superior parietal lobule, middle and superior precentral gyri and left frontal pole. These findings reveal that altercentric interference relies on areas involved in self-other distinction, self-updating and central executive functions. In contrast, egocentric interference needs the activation of the mirror neuron system and deductive reasoning, much less related to pure ToM abilities.

Wearing a KN95/FFP2 facemask induces subtle yet significant brain functional connectivity modifications restricted to the salience network.

BACKGROUND: The use of facemasks is one of the consequences of the coronavirus disease 2019 (COVID-19) pandemic. We used resting-state functional magnetic resonance imaging (fMRI) to search for subtle changes in brain functional connectivity, expected notably related to the high-level salience network (SN) and default mode network (DMN). METHODS: Prospective crossover design resting 3-T fMRI study with/without wearing a tight FFP2/KN95 facemask, including 23 community-dwelling male healthy controls aged 29.9 ± 6.9 years (mean ± standard deviation). Physiological parameters, respiration frequency, and heart rate were monitored. The data analysis was performed using the CONN toolbox. RESULTS: Wearing an FFP2/KN95 facemask did not impact respiration or heart rate but resulted in a significant reduction in functional connectivity between the SN as the seed region and the left middle frontal and precentral gyrus. No difference was found when the DMN, sensorimotor, visual, dorsal attention, or language networks were used as seed regions. In the absence of significant changes of physiological parameter respiration and heart rate, and in the absence of changes in lower-level functional networks, we assume that those subtle modifications are cognitive consequence of wearing facemasks. CONCLUSIONS: The effect of wearing a tight FFP2/KN95 facemask in men is limited to high-level functional networks. Using the SN as seed network, we observed subtle yet significant decreases between the SN and the left middle frontal and precentral gyrus. Our observations suggest that wearing a facemask may change the patterns of functional connectivity with the SN known to be involved in communication, social behavior, and self-awareness.

Cognitive and Emotional Determinants of Automatic Perspective Taking in Healthy Adults.

Previous studies using the dot-perspective task postulated that people automatically take into account others' perspective even when it prevents them from achieving their own goals. This human ability may be of key importance for the ascription of mental states and social interactions. The cognitive and emotional determinants of automatic perspective taking (APT) is still matter of debate. To address this issue, we examined the performance in the Samson et al. APT task in 91 healthy adults who underwent a detailed neuropsychological testing including assessment of their general intelligence (Wechsler Adult Intelligence Scale, WAIS), attention and impulsivity (Conners' Continuous Performance Test-II, CPT-II), alexithymia (Toronto Alexithymia Scale, TAS), and measures of affective empathy and explicit theory of mind (Geneva Social Cognition Scale, GeSoCS, and mini-Social cognition and Emotional Assessment, mini-SEA). Univariate and multiple linear regression models (adjusted for age, gender, and education) were used to explore the association between mean reaction times (respectively, mean number of errors) in the APT task, and the CPT-II parameters, WAIS global score (as well as subscale scores), TAS, and GeSoCS and mini-SEA scores. Only the CPT-II parameters were significantly associated with the mean reaction times. Increased omissions, commissions, and detectability as well as hit reaction time standard error in CPT-II were all related to worse performances both in Self and Other conditions. The mean number of errors was negatively associated with the GeSoCS score. Among the variables studied, only CPT-II parameters had a significant impact on egocentric and altercentric interference. Neither global intelligence nor alexithymia have an effect on dot-perspective task performance. The present findings suggest that people with lower attentional resources and increased impulsivity display worse performances in the APT task and are less responsive to both egocentric and altercentric interference.

Personality Impact on Alzheimer's Disease - Signature and Vascular Imaging Markers: A PET-MRI Study.

BACKGROUND: Several studies postulated that personality is an independent determinant of cognitive trajectories in old age. OBJECTIVE: This study explores the impact of personality on widely used Alzheimer's disease (AD) and vascular imaging markers. METHODS: We examined the association between personality and three classical AD imaging markers (centiloid-based-amyloid load, MRI volumetry in hippocampus, and media temporal lobe atrophy), and two vascular MRI parameters (Fazekas score and number of cortical microbleeds) assessed at baseline and upon a 54-month-follow-up. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of imaging markers including sex, personality factors, presence of APOE ɛ4 allele and cognitive evolution over time. RESULTS: Cortical GM volumes were negatively associated with higher levels of Conscientiousness both at baseline and follow-up. In contrast, higher scores of Openness were related to better preservation of left hippocampal volumes in these two time points and negatively associated with medial temporal atrophy at baseline. Amyloid load was not affected by personality factors. Cases with higher Extraversion scores displayed higher numbers of cortical microbleeds at baseline. CONCLUSION: Personality impact on brain morphometry is detected only in some among the routinely used imaging markers. The most robust associations concern the positive role of high levels of Conscientiousness and Openness on AD-signature MRI markers. Higher extraversion levels are associated with increased vulnerability to cortical microbleeds pointing to the fact that the socially favorable traits may have a detrimental effect on brain integrity in old age.

Early-phase 18F-Florbetapir and 18F-Flutemetamol images as proxies of brain metabolism in a memory clinic setting.

Background: Alzheimer's disease (AD) neuropathologic changes are ß-amyloid (Aß) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid-PET might be able to evaluate Aß deposition and neurodegeneration with a single tracer injection. Early-phase amyloid-PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late frames depict amyloid distribution. Our study aims to assess the comparability between early-phase amyloid-PET scans and 18F-fluorodeoxyglucose (18F-FDG)-PET brain topography at the individual level, and their ability to discriminate patients. Methods: 166 subjects evaluated at the Geneva Memory Center, ranging from cognitively unimpaired to Mild Cognitive Impairment (MCI) and dementia, underwent early-phase amyloid-PET - using either 18F-florbetapir (eFBP) (n = 94) or 18F-flutemetamol (eFMM) (n = 72) - and 18F-FDG-PET. Aß status was assessed. Standardized uptake value ratios (SUVR) were extracted to evaluate the correlation of eFBP/eFMM and their respective 18F-FDG-PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by Dice coefficient. Receiver operating characteristic analyses were performed to compare the discriminative power of eFBP/eFMM, and 18F-FDG-PET SUVR in AD-related metaROI between Aß-negative healthy controls and cases in the AD continuum. Results: Positive correlations were found between eFBP/eFMM and 18F-FDG-PET SUVR independently of Aß status and Aß radiotracer (R>0.72, p<0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabolism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and 18F-FDG-PET SUVR significantly discriminated AD patients from controls in the AD-related metaROIs (AUCFBP = 0.888; AUCFMM=0.801), with 18F-FDG-PET performing slightly better, however not significantly (all p-value higher than 0.05), than others (AUCFDG=0.915 and 0.832 for subjects evaluated with 18F-FBP and 18F-FMM, respectively). Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP/eFMM imaging can replace 18F-FDG-PET imaging, as they reveal typical neurodegenerative patterns, or allow to exclude the presence of neurodegeneration. The finding shows cost-saving capacities of amyloid-PET and supports the routine use of the modality for individual classification in clinical practice.

Determinants of Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study in a Community-based Cohort.

BACKGROUND: The determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals. OBJECTIVE: The current research aimed to identify the main determinants associated with cognitive trajectories in normal aging. METHODS: We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral microbleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PIR. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables. RESULTS: The number of strictly lobar CMB at baseline (4 or more) was related to a significant increase in the risk of cognitive decrement. In multivariable models, amyloid positivity was associated with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was related to better preservation of neuropsychological performances. CONCLUSION: CMB and amyloid positivity are the only imaging determinants of cognitive trajectories in this highly selected series of healthy controls. Among personality factors, higher agreeableness confers a modest but significant protection against the decline of cognitive performances.

Prediction of Subtle Cognitive Decline in Normal Aging: Added Value of Quantitative MRI and PET Imaging.

Quantitative imaging processing tools have been proposed to improve clinic-radiological correlations but their added value at the initial stages of cognitive decline is still a matter of debate. We performed a longitudinal study in 90 community-dwelling elders with three neuropsychological assessments during a 4.5 year follow-up period, and visual assessment of medial temporal atrophy (MTA), white matter hyperintensities, cortical microbleeds (CMB) as well as amyloid positivity, and presence of abnormal FDG-PET patterns. Quantitative imaging data concerned ROI analysis of MRI volume, amyloid burden, and FDG-PET metabolism in several AD-signature areas. Multiple regression models, likelihood-ratio tests, and areas under the receiver operating characteristic curve (AUC) were used to compare quantitative imaging markers to visual inspection. The presence of more or equal to four CMB at inclusion and slight atrophy of the right MTL at follow-up were the only parameters to be independently related to the worst cognitive score explaining 6% of its variance. This percentage increased to 24.5% when the ROI-defined volume loss in the posterior cingulate cortex, baseline hippocampus volume, and MTL metabolism were also considered. When binary classification of cognition was made, the area under the ROC curve increased from 0.69 for the qualitative to 0.79 for the mixed imaging model. Our data reveal that the inclusion of quantitative imaging data significantly increases the prediction of cognitive changes in elderly controls compared to the single consideration of visual inspection.