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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.

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.

BackgroundWide use of wearing a facemask is one of the many consequences of the COVID-19 pandemic. We used resting-state fMRI to search for subtle changes in brain functional connectivity, expected notably related to the high-level salience (SN) and default mode networks (DMN).Materials and MethodsProspective crossover design resting fMRI study with/without wearing a tight FFP2/KN95 facemask, including 24 consecutive male participants (mean age ± SD = 29.9 ± 6.9 years) at 3T. As physiological parameters, respiration frequency and heart rate were monitored. Data analysis was performed using the CONN toolbox.ResultsWearing 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.ConclusionsThe wearing of tight FFP2/KN95 facemasks in men decreases the functional connectivity of the SN, which is known to be involved in communication, social behavior and self-awareness. This phenomenon was confined to the left frontal and precentral gyrus. Our results imply that the wearing of a facemask could impact our ability to detect and react appropriately to salient stimuli by altering the functional connectivity of the SN.

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.

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.

Mesial temporal lobe (MTL) is prominently affected in normal aging and associated with neurodegeneration in AD. Whether or not MTL atrophy is dependent on increasing amyloid load before the emergence of cognitive deficits is still disputed. We performed a 4.5-year longitudinal study in 75 older community dwellers (48 women, mean age: 79.3 years) including magnetic resonance imaging at baseline and follow-up, positron emission tomography amyloid during follow-up, neuropsychological assessment at 18 and 55 months, and APOE genotyping. Linear regression models were used to identify predictors of the MTL volume loss. Amyloid load was negatively associated with bilateral MTL volume at baseline explaining almost 10.5% of its variability. In multivariate models including time of follow-up and demographic variables (older age, male gender), this percentage exceeded 35%. The APOE4 allele independently contributed another 6%. Cognitive changes had a modest but still significant negative association with MTL volume loss. Our data support a multifactorial model including amyloid deposition, older age, male gender, APOE4 allele, and slight decline of cognitive abilities as independent predictors of MTL volume loss in brain aging.

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 Aβ-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 Aβ-index method. Compared to the visual rating, Aβ-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 Aβ-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.

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.

BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline. MATERIALS AND METHODS: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients. RESULTS: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%–31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22–0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds. CONCLUSIONS: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.

Background/Aims: Recent studies of cases with mild cognitive impairment (MCI) suggested that besides Alzheimer disease (AD)-related biomarkers, some personality dimensions are associated with progression to AD. To date, there are no studies addressing the psychological determinants of subtle cognitive decline in healthy elderly controls. Methods: 488 community-dwelling healthy controls were assessed with a detailed neuropsychological battery at baseline and an 18-month follow-up. Personality factors and facets were investigated at baseline using the NEO-Personality Inventory-Revised (NEO-PI-R). Upon follow-up, there were 264 stable controls (sCON) and 224 deteriorating controls (dCON). Their personality data were compared to those of the 102 MCI cases using one-way analysis of variance and logistic regression models. Results: Significantly higher scores of Openness factor (as well as Aesthetics, Ideas and Values facets) were found in sCON than in both dCON and MCI cases. The three groups did not differ in the other NEO-PI-R factor and facet scores. Openess factor (and the same facets) was associated with cognitive preservation in healthy controls (OR: 0.72, 95% CI: 0.59, 0.87). Lower scores in the same factor and facets conferred higher risk to have MCI (OR: 0.61, 95% CI: 0.46, 0.79). Conclusion: Higher openness to new experiences and thoughts may be a protective factor against early cognitive decline in brain aging.

BACKGROUND AND PURPOSE:Multidelay arterial spin-labeling is a promising emerging method in clinical practice. The effect of imaging parameters in multidelay arterial spin-labeling on estimated cerebral blood flow measurements remains unknown. We directly compared 3-delay versus 7-delay sequences, assessing the difference in the estimated transit time and blood flow. MATERIALS AND METHODS:This study included 87 cognitively healthy controls (78.7 3.8 years of age; 49 women). We assessed delay and transit time-uncorrected and transit time-corrected CBF maps. Data analysis included voxelwise permutation-based between-sequence comparisons of 3-delay versus 7-delay, within-sequence comparison of transit time-uncorrected versus transit time-corrected maps, and average CBF calculations in regions that have been shown to differ. RESULTS:The 7-delay sequence estimated a higher CBF value than the 3-delay for the transit time-uncorrected and transit time-corrected maps in regions corresponding to the watershed areas (transit time-uncorrected = 27.62 +/- 12.23 versus 24.58 +/- 11.70 mL/min/100 g, Cohen's d = 0.25; transit time-corrected = 33.48 +/- 14.92 versus 30.16 +/- 14.32 mL/min/100 g, Cohen's d = 0.23). In the peripheral regions of the brain, the estimated delay was found to be longer for the 3-delay sequence (1.52408 +/- 0.25236 seconds versus 1.47755 +/- 0.24242 seconds, Cohen's d = 0.19), while the inverse was found in the center of the brain (1.39388 +/- 0.22056 seconds versus 1.42565 +/- 0.21872 seconds, Cohen's d = 0.14). Moreover, 7-delay had lower hemispheric asymmetry. CONCLUSIONS:The results of this study support the necessity of standardizing acquisition parameters in multidelay arterial spin-labeling and identifying basic parameters as a confounding factor in CBF quantification studies. Our findings conclude that multidelay arterial spin-labeling sequences with a high number of delays estimate higher CBF values than those with a lower number of delays.

Resting-state functional magnetic resonance imaging (RS-fMRI) is based on the assumption that the vascular response and the blood oxygenation level-dependent response are homogenous across the entire brain. However, this a priori hypothesis is not consistent with the well-known variability of cerebral vascular territories. To explore whether the RS networks are influenced by varied vascular speed in different vascular territories, we assessed the time-shift maps that give an estimate of the local timing of the vascular response and checked whether local differences in this timing have an impact on the estimates of RS networks. Two hundred seventeen elderly (≥60 years), healthy participants (73.74 ± 4.41 years, 143 females, 203 right handed) underwent one MRI examination, including an RS-fMRI session. After preprocessing, statistical analyses included time-shift analyses and RS-fMRI analyses using as regressor the delay maps obtained from the time-shift analyses. The functional connectivity map of default mode network (DMN) of each participant was then calculated by using the seed-to-voxel analysis in the REST toolbox. Faster cerebrovascular responses were notably present in the primary motor and somatosensory and peri-insular cortex, while slower responses were present in various regions, including notably the posterior cingulate cortex (PCC). Moreover, significant changes notably in the DMN, including medial prefrontal cortex (t = 11.95), PCC (t = 11.52), right middle temporal lobe (t = 10.72), and right angular gyrus (t = 10.88), were observed also taking into account the cerebrovascular delayed maps. As the most prominent example of the RS networks, DMN activation patterns change as a function of the cerebrovascular delay. These data suggest that a group correction for vascular maps in RS-fMRI measurements is essential to correctly depict functional differences and exclude potential confounding effects, notably in the elderly with increasing prevalence of vascular comorbidity.

BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline. MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM. RESULTS: APOE*E4-related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE*E4-related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up. CONCLUSIONS: APOE*E4-related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE*E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe.

In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior-posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in these vulnerable cases.

Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

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. Key Points • Many forms of dementia have spatial atrophy patterns detectable on neuroimaging. • Early treatment of dementia is beneficial, indicating the need for early diagnosis. • Advanced image analysis techniques detect subtle anomalies invisible on radiological evaluation. • Inter-individual variation explains variable cognitive impairment despite the same degree of atrophy.

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. 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. Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p

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.

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD.

Coffee, wine and chocolate are three frequently consumed substances with a significant impact on cognition. In order to define the structural and cerebral blood flow correlates of self-reported consumption of coffee, wine and chocolate in old age, we assessed cognition and brain MRI measures in 145 community-based elderly individuals with preserved cognition (69 to 86 years). Based on two neuropsychological assessments during a 3-year follow-up, individuals were classified into stable-stable (52 sCON), intermediate (61 iCON) and deteriorating-deteriorating (32 dCON). MR imaging included voxel-based morphometry (VBM), tract-based spatial statistics (TBSS) and arterial spin labelling (ASL). Concerning behavior, moderate consumption of caffeine was related to better cognitive outcome. In contrast, increased consumption of wine was related to an unfavorable cognitive evolution. Concerning MRI, we observed a negative correlation of wine and VBM in bilateral deep white matter (WM) regions across all individuals, indicating less WM lesions. Only in sCON individuals, we observed a similar yet weaker association with caffeine. Moreover, again only in sCON individuals, we observed a significant positive correlation between ASL and wine in overlapping left parietal WM indicating better baseline brain perfusion. In conclusion, the present observations demonstrate an inverse association of wine and coffee consumption with cognitive performances. Moreover, low consumption of wine but also moderate to heavy coffee drinking was associated with better WM preservation and cerebral blood-flow notably in cognitively stable elders.

Resting-state functional MRI (rs-fMRI) opens a window on large-scale organization of brain function. However, establishing relationships between resting-state brain activity and cognitive or clinical scores is still a difficult task, in particular in terms of prediction as would be meaningful for clinical applications such as early diagnosis of Alzheimer's disease. In this work, we employed partial least square regression under cross-validation scheme to predict episodic memory performance from functional connectivity (FC) patterns in a set of fifty-five MCI subjects for whom rs-fMRI acquisition and neuropsychological evaluation was carried out. We show that a newly introduced FC measure capturing the moments of anti-correlation between brain areas, discordance, contains key information to predict long-term memory scores in MCI patients, and performs better than standard measures of correlation to do so. Our results highlighted that stronger discordance within default mode network (DMN) areas, as well as across DMN, attentional and limbic networks, favor episodic memory performance in MCI., Highlights • We use PLS to predict memory scores from resting-state fMRI. • We compare prediction performance of different functional connectivity measures. • We highlight the role of anti-correlation in memory-score prediction. • We highlight the role of default-mode network in episodic memory.

An important question in neuroscience is to reveal the relationship between individual performance and brain activity. This could be achieved by applying model regression techniques, in which functional connectivity derived from resting-state functional magnetic resonance imaging (fMRI), is used as a predictor. However, due to the large number of parameters, prediction becomes problematic and regression models cannot be found using the traditional least squares method. We study the ability of fMRI data to predict long-term-memory scores in mild cognitive impairment subjects, using partial least squares regression, which is an adapted method for high-dimensional regression problems. We also study the influence of the sample size on the performance, the stability and the reproducibility of the prediction.

Future treatments of Alzheimer's disease need the identification of cases at high risk at the preclinical stage of the disease before the development of irreversible structural damage. We investigated here whether subtle cognitive deterioration in a population of healthy elderly individuals could be predicted by EEG signals at baseline under cognitive activation. Continuous EEG was recorded in 97 elderly control subjects and 45 age-matched mild cognitive impairment (MCI) cases during a simple attentional and a 2-back working memory task. Upon 18-month neuropsychological follow-up, the final sample included 55 stable (sCON) and 42 deteriorated (dCON) controls. We examined the P1, N1, P3, and PNwm event-related components as well as the oscillatory activities in the theta (4-7 Hz), alpha (8-13 Hz), and beta (14-25 Hz) frequency ranges (ERD/ERS: event-related desynchronization/synchronization, and ITC: inter-trial coherence). Behavioral performance, P1, and N1 components were comparable in all groups. The P3, PNwm, and all oscillatory activity indices were altered in MCI cases compared to controls. Only three EEG indices distinguished the two control groups: alpha and beta ERD (dCON > sCON) and beta ITC (dCON < sCON). These findings show that subtle cognitive deterioration has no impact on EEG indices associated with perception, discrimination, and working memory processes but mostly affects attention, resulting in an enhanced recruitment of attentional resources. In addition, cognitive decline alters neural firing synchronization at high frequencies (14-25 Hz) at early stages, and possibly affects lower frequencies (4-13 Hz) only at more severe stages.

Previous contributions in younger cohorts have revealed that reallocation of cerebral resources, a crucial mechanism for working memory (WM), may be disrupted by parallel demands of background acoustic noise suppression. To date, no study has explored the impact of such disruption on brain activation in elderly individuals with or without subtle cognitive deficits. We performed a functional Magnetic Resonance Imaging (fMRI) study in 23 cases (mean age=75.7 y.o., 16 men) with mild cognitive impairment (MCI) and 16 elderly healthy controls (HC, mean age=70.1 y.o., three men) using a 2-back WM task, under two distinct MRI background acoustic noise conditions (louder vs. lower noise echo-planar imaging). General linear models were used to assess brain activation as a function of group and noise. In both groups, lower background noise is associated with increased activation of the working memory network (WMN). A decrease of the normally observed deactivation of the default mode network (DMN) is found under louder noise in both groups. Unlike HC, MCI cases also show decreased deactivation of the DMN under both louder and lower background noise. Under louder noise, this decrease is observed in anterior parts of the DMN in HC, and in the posterior cingulate cortex in MCI cases. Our results suggest that background acoustic noise has a differential impact on WMN activation in normal aging as a function of the cognitive status. Only louder noise has a disruptive effect on the usually observed DMN deactivation during WM task performance in HC. In contrast, MCI cases show altered DMN reactivity even in the presence of lower noise.