Clémence Tomadesso

Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood

Recent studies in mouse models of Alzheimers disease (AD) and in humans suggest that sleep disruption and amyloid-beta (Aβ) accumulation are interrelated, and may, thus, exacerbate each other. We investigated the association between self-reported sleep variables and neuroimaging data in 51 healthy older adults. Participants completed a questionnaire assessing sleep quality and quantity and underwent positron emission tomography scans using [18F]florbetapir and [18F]fluorodeoxyglucose and an magnetic resonance imaging scan to measure Aβ burden, hypometabolism, and atrophy, respectively. Longer sleep latency was associated with greater Aβ burden in prefrontal areas. Moreover, the number of nocturnal awakenings was negatively correlated with gray matter volume in the insular region. In asymptomatic middle-aged and older adults, lower self-reported sleep quality was associated with greater Aβ burden and lower volume in brain areas relevant in aging and AD, but not with glucose metabolism. These results highlight the potential relevance of preserving sleep quality in older adults and suggest that sleep may be a factor to screen for in individuals at risk for AD.

Hippocampal Subfield Volumetry and 3D Surface Mapping in Subjective Cognitive Decline.

BACKGROUND Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimers disease (AD). SCD individuals with normal cognition may already have significant hippocampal atrophy, a well-known feature of AD. OBJECTIVE To test the hypothesis that SCD, compared to healthy individuals without SCD, have a pattern of hippocampal subfield atrophy similar to that measured in the AD pathology. METHODS 17 SCD, 21 AD, and 40 matched controls underwent a standard T1-weighted MRI and a dedicated high-resolution MRI proton-density hippocampal sequence. For each participant, three hippocampal regions-of-interest were manually delineated on the proton-density hippocampal sequence corresponding to the CA1, subiculum, and other (including CA2-3-4 and dentate gyrus) subfields. Total intracranial volume (TIV)-normalized subfield volumes were compared between-group. Voxelwise group comparisons assessed from the standard T1 MRI were also projected on 3D hippocampal surface views. RESULTS Both patient groups showed significant TIV-normalized volume decrease in hippocampus global volume and in CA1 and subiculum subfields as well as in the other subfield in AD compared to controls. Significant differences were observed between SCD and AD in hippocampus global TIV-normalized volume. Atrophy maps on hippocampal surface showed major involvement of the lateral part (CA1) in both SCD and AD, with larger overlap of other regions in AD. CONCLUSION The findings indicate topographically similar hippocampal subfield changes in SCD individuals as those found in AD. This further highlights the relevance of SCD recruited from a memory clinic in assessing pre-dementia AD stages.

Qualitative and quantitative assessment of self-reported cognitive difficulties in nondemented elders: Association with medical help seeking, cognitive deficits, and β-amyloid imaging

Subjective cognitive decline (SCD) could help identify early stages of Alzheimers disease. However, SCD is multidetermined and protean, and the type of cognitive complaint associated with preclinical Alzheimers disease needs refinement.

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment.

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimers disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.

Connectivity Disruption, Atrophy, and Hypometabolism within Posterior Cingulate Networks in Alzheimer's Disease

The posterior cingulate cortex (PCC) is a critical brain network hub particularly sensitive to Alzheimers disease (AD) and can be subdivided into ventral (vPCC) and dorsal (dPCC) regions. The aim of the present study was to highlight functional connectivity (FC) disruption, atrophy, and hypometabolism within the ventral and dorsal PCC networks in patients with amnestic mild cognitive impairment (aMCI) or AD. Forty-three healthy elders (HE) (68.7 ± 6 years), 34 aMCI (73.4 ± 6.8 years) and 24 AD (70.9 ± 9.1 years) patients underwent resting-state functional MRI, anatomical T1-weighted MRI and FDG-PET scans. We compared FC maps obtained from the vPCC and dPCC seeds in HE to identify the ventral and dorsal PCC networks. We then compared patients and HE on FC, gray matter volume and metabolism within each network. In HE, the ventral PCC network involved the hippocampus and posterior occipitotemporal and temporoparietal regions, whereas the dorsal PCC network included mainly frontal, middle temporal and temporoparietal areas. aMCI patients had impaired ventral network FC in the bilateral hippocampus, but dorsal network FC was preserved. In AD, the ventral network FC disruption had spread to the left parahippocampal and angular regions, while the dorsal network FC was also affected in the right middle temporal cortex. The ventral network was atrophied in the bilateral hippocampus in aMCI patients, and in the vPCC and angular regions as well in AD patients. The dorsal network was only atrophied in AD patients, in the dPCC, bilateral supramarginal and temporal regions. By contrast, hypometabolism was already present in both the vPCC and dPCC networks in aMCI patients, and further extended to include the whole networks in AD patients. The vPCC and dPCC connectivity networks were differentially sensitive to AD. Atrophy and FC disruption were only present in the vPCC network in aMCI patients, and extended to the dPCC network in AD patients, suggesting that the pathology spreads from the vPCC to the dPCC networks. By contrast, hypometabolism seemed to follow a different route, as it was present in both networks since the aMCI stage, possibly reflecting not only local disruption but also distant synaptic dysfunction.

Reduced age-associated brain changes in expert meditators: a multimodal neuroimaging pilot study

Aging is associated with progressive cerebral volume and glucose metabolism decreases. Conditions such as stress and sleep difficulties exacerbate these changes and are risk factors for Alzheimer’s disease. Meditation practice, aiming towards stress reduction and emotion regulation, can downregulate these adverse factors. In this pilot study, we explored the possibility that lifelong meditation practice might reduce age-related brain changes by comparing structural MRI and FDG-PET data in 6 elderly expert meditators versus 67 elderly controls. We found increased gray matter volume and/or FDG metabolism in elderly expert meditators compared to controls in the bilateral ventromedial prefrontal and anterior cingulate cortex, insula, temporo-parietal junction, and posterior cingulate cortex /precuneus. Most of these regions were also those exhibiting the strongest effects of age when assessed in a cohort of 186 controls aged 20 to 87 years. Moreover, complementary analyses showed that these changes were still observed when adjusting for lifestyle factors or using a smaller group of controls matched for education. Pending replication in a larger cohort of elderly expert meditators and longitudinal studies, these findings suggest that meditation practice could reduce age-associated structural and functional brain changes.

Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients: Hippocampal Subfields Connectivity

Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty‐six HE and 27 aMCI patients underwent resting‐state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high‐resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922–4932, 2017.

INTERPLAY BETWEEN BASELINE AND LONGITUDINAL CHANGE IN NEUROIMAGING MARKERS OF AMYLOID DEPOSITION AND NEURODEGENERATION ACROSS THE ALZHEIMER’S DISEASE SPECTRUM

modality associations between baseline and longitudinal change of each imaging modality. Linear mixed effects analyses were performed using R (nlme package) to estimate the effect of baseline on rate of change over time, whilst incorporating the longitudinal nature of the data by including within-person variation as random effects. Age at baseline and sex were included as covariates in all models. Models can be summarized as follow: Intra-modality relationship/ (Modalityl Annual Rate of Change)Region i w (Baseline Modalityl)Region j + Age + Sex + (1 j Subject) Inter-modality relationship/ (Modalityl Annual Rate of Change)Region i w (Baseline Modality2)Region js + Age + Sex + (1 j Subject) whereModality corresponds to volume, FDGor AV45-SUVR, and Region i and Region j represent one bilateral ROIs of the Harvard-Oxford structural atlas. Note that on the heatmaps, ROIs are shown in the same order for xand y-axis. Therefore, the upper diagonal represents the relationships when the Figure 2. regions showing GM atrophyi n NC-p (in green), NC-s (in blue), and group-interaction (in red). Poster Presentations: Saturday, July 21, 2018 P111

Neuropsychology and neuroimaging profiles of amyloid-positive versus amyloid-negative amnestic mild cognitive impairment patients

Patients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. The present study aimed at highlighting the neuropsychological, brain atrophy, and hypometabolism profiles of amyloid‐positive (Aβpos) versus amyloid‐negative (Aβneg) aMCI patients.

AMYLOID-POSITIVE VERSUS NEGATIVE AMCI: SIMILARITIES AND DIFFERENCES IN NEUROPSYCHOLOGY AND NEUROIMAGING PROFILES

tion and neuropsychological tests including the SubjectiveMemory Complaints Questionnaire(SMCQ), Seoul Informant Report Questionnaire for Dementia(SIRQD), Clinical Dementia Rating(CDR), CERAD neuropsychological battery, stroop test as well as Apolipoprotein E(APOE) allele typing, MRI, and Pittsburgh compound B PET(Pib PET). PiB PET Images were classified as amyloid deposition positive if the mean C-PiB retention value was over 1.4 in one of the following regions: the frontal, lateral temporal, lateral parietal, precuneus/posterior cingulate cortices. In MRI, we measured mean gray matter(GM) thickness using freesurfer. Results:Among 30 subjects, 18 subjects classified as amyloid deposition positive group(MCI+). Compared to amyloid deposition negative(MCI-) group, MCI+ group showed significantly higher APOE e4 allele frequency, lower word list recall, higher stroop color-word test scores and lower mean cortical thickness in MRI. When amyloid deposition positivity prediction models based on logistic regression analyses were compared, the combined model of CERAD word list recall, stroop color word test, and MRI mean cortical thickness was the best discrimination model after adjusting age, education, and APOE e4 allele frequency(the prediction accuracy 90 %). Conclusions:Our results suggest that the combination of verbal delayed recall, stroop color-word test, and cortical thickness on MRI may be useful for the discrimination of amyloid deposition status.