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.

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.

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.

The Special Care Unit for People with Behavioral and Psychological Symptoms of Dementia (SCU- B) in the Context of the Project "RECage-Respectful Caring for Agitated Elderly": A Qualitative Study.

BACKGROUND: Dementia is a priority for global public health. The management of behavioral and psychological symptoms of dementia (BPSD) is one of the highest ongoing challenges and needs new approaches. The special care unit for people with dementia and BPSD (SCU-B) is viewed in this context as a further medical intervention. AIM: this study aims to explore SCU-B units in order to describe their main characteristics in relation to different implementation contexts, identify the characteristics of their replicability, and examine the social innovation elements promoted by SCU-B units. METHOD: This qualitative study is based on focus groups (FGs) and interviews involving nine international centers. Five of the centers have a memory clinic unit and SCU-B, compared with six that only have a memory clinic unit. A total number of 18 FGs were held, which altogether involved 164 participants. All data were transcribed verbatim and analyzed by means of a content analysis and a SWOT (strengths, weaknesses, opportunities, and threats) analysis. RESULTS: The qualitative analysis offers a vision of the SCU-B model as an innovative care unit for BPSD, promoting social innovation in the long-term care (LTC) sector. This system mainly targets people with dementia and BPSD and their informal caregivers but encourages collaboration between dementia care stakeholders at the micro and meso levels. CONCLUSIONS: Specific characteristics of the country's LTC systems and the organization of specialized units are determinants for the success of the SCU-B experience. The replicability of the entire SCU-B model was considered low; however, the implementation of single elements composing the SCU-B model may foster innovation. This study provides relevant suggestions on how to implement the SCU-B unit and innovative solutions for dementia care.

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.

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.

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.

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.

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.

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.

Identification of hippocampal cortical microinfarcts on postmortem 3-T magnetic resonance imaging.

Cortical microinfarcts (CMI) are increasingly recognized in the neurological community as a biomarker related to cognitive impairment and dementia. If their radiological depiction has been largely described in experimental settings using ultra-high-field magnetic resonance imaging (MRI), less is known about their visibility on routinely used 3-T MRI. In this radiologic-pathologic correlation study, using 3-T post-mortem MRI, we searched for hippocampal CMI, in a double-blinded fashion, and found that only 4/36, or 11%, were clearly demonstrated on both radiological and histopathological exams.

Personality Factors' Impact on the Structural Integrity of Mentalizing Network in Old Age: A Combined PET-MRI Study.

The mentalizing network (MN) treats social interactions based on our understanding of other people's intentions and includes the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), posterior cingulate cortex (PCC), precuneus (PC), and amygdala. Not all elders are equally affected by the aging-related decrease of mentalizing abilities. Personality has recently emerged as a strong determinant of functional connectivity in MN areas. However, its impact on volumetric changes across the MN in brain aging is still unknown. To address this issue, we explored the determinants of volume decrease in MN components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models corrected for multiple comparisons were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. In cases with higher Agreeableness scores, there were lower volume losses in PCC, PC, and amygdala bilaterally. This was also the case for the right mPFC in elders displaying lower Agreeableness and Conscientiousness. In multiple regression models, the effect of Agreeableness was still observed in left PC and right amygdala and that of Conscientiousness was still observed in right mPFC volume loss (26.3% of variability, significant age and sex). Several Agreeableness (Modesty) and Conscientiousness (order, dutifulness, achievement striving, and self-discipline) facets were positively related to increased volume loss in cortical components of the MN. In conclusion, these data challenge the beneficial role of higher levels of Agreeableness and Conscientiousness in old age, showing that they are associated with an increased rate of volume loss within the MN.

PET amyloid in normal aging: direct comparison of visual and automatic processing methods.

Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic Aß-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of - 3.045 for the Aß-index method. Compared to the visual rating, Aß-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of - 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the Aß-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The Aß-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.

Microbleeds and Medial Temporal Atrophy Determine Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study.

BACKGROUND: The cognitive trajectories in normal aging may be affected by medial temporal atrophy (MTA) and amyloid burden, as well as vascular pathologies such as cortical microbleeds (CMB) and white matter hyperintensities (WMH). OBJECTIVE: We addressed here the role of imaging markers in their prediction in a real-world situation. METHODS: We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, MTA estimated with the Schelten's scale, number of CMB, and WMH evaluated with the Fazekas score at inclusion and follow-up, visual rating of amyloid PET and glucose hypometabolism at follow-up, and APOE genotyping. Regression models were built to explore the association between the continuous cognitive score (CCS) and imaging parameters. RESULTS: The number of strictly lobar CMB at baseline (4 or more) was related to a 5.5-fold increase of the risk of cognitive decrement. This association persisted in multivariable models explaining 10.6% of the CCS decrease variance. MTA, and Fazekas score at baseline and amyloid positivity or abnormal FDG PET, were not related to the cognitive outcome. The increase of right MTA at follow-up was the only correlate of CCS decrease both in univariate and multivariable models explaining 9.2% of its variance. CONCLUSION: The present data show that the accumulation of more than four CMB is associated with significant cognitive decrement over time in highly educated elderly persons. They also reveal that the progressive deterioration of cognitive performance within the age-adjusted norms is also related to the increase of visually assessed MTA.

Medial temporal lobe volume is associated with neuronal loss but not with hippocampal microinfarcts despite their high frequency in aging brains.

Medial temporal lobe (MTL) atrophy is an important marker for the clinical diagnosis of Alzheimer's disease at its prodromal stages. Several brain lesions have been associated with MTL atrophy including hippocampal sclerosis, neurodegenerative neuronal loss, and vascular pathology. To better explore the relationship between MTL volume on MRI and age-related degenerative and microvascular hippocampal pathology, we compared MTL volume on postmortem whole brain MRI and stereological estimates of the total number of neurons, cortical microinfarcts (CMIs), and neurofibrillary tangles (NFTs) in a consecutive autopsy series of 21 older individuals (11 females and 10 males, mean age 83.3 ± 5.8; range: 74-93 years, 7 demented and 14 nondemented). Our results revealed a very high percentage of cases with hippocampal CMIs (52%), particularly in the CA1 field. MTL volume was closely related to neuronal loss in both the CA1 area of the hippocampus (p = 0.0109) and the entorhinal cortex (p = 0.0272). MTL volume was not related to total CMI volume or to the total number of NFTs in our sample. In conclusion, hippocampal CMIs are very common in old age. MTL volume is determined essentially by the number of neurons in the hippocampus and does not appear to be related to the presence of NFTs or CMIs in this region.

How non-drug interventions affect the quality of life of patients suffering from progressive cognitive decline and their main caregiver.

BACKGROUND: In the absence of cure for age-related neurodegenerative diseases, non-drug interventions (NDIs) represent useful options. Quality of life (QOL) is a multidimensional concept progressively affected by cognitive decline. How single or multiple NDIs impact QOL is unknown. RESULTS: We found no significant effect of multiple over single NDI on QOL. Socio-demographic variables influenced patients' (age, gender, caregivers' occupational status, management of patients' financial affairs) and caregivers' (gender, occupational status, patients' severity of cognitive decline) QOL. When dyads interrupted interventions after 6 months, their QOL was lower and caregivers' anxiety, depression and physical symptoms were higher at the end of the study. CONCLUSIONS: While the type and number of interventions do not appear to be critical, the continuity of adapted interventions in the long-term might be important for maintaining QOL of patients and caregivers. METHODS: This is a multicenter (7 Swiss Memory Clinics), quasi-experimental, one-year follow-up study including 148 subjects (mild cognitive impairment or mild dementia patients and their caregivers). Primary outcome was the effect of multiple vs single NDIs on QOL. Secondary outcome included NDIs effect on patients' cognitive impairment and functional autonomy, caregivers' burden, severity of patients' neuropsychiatric symptoms and dyads' anxiety and depression.