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Article ; Online: The Psychological Impact of the Coronavirus Pandemic and the Importance of Resilience.

Vannini, Patrizia

Biological psychiatry. Cognitive neuroscience and neuroimaging

2024 Volume 8, Issue 2, Page(s) 133–134

MeSH term(s)	Humans ; Pandemics ; COVID-19 ; Mental Health
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2022.12.001
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Article: Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment.

Gagliardi, Geoffroy / Vannini, Patrizia

Frontiers in aging neuroscience

2022 Volume 13, Page(s) 802501

Abstract: Introduction: Loss of awareness is a common symptom in Alzheimer's Disease (AD) and responsible for a significant loss of functional abilities. The mechanisms underlying loss of awareness in AD is unknown, although previous findings have implicated ... ...

Abstract	Introduction: Loss of awareness is a common symptom in Alzheimer's Disease (AD) and responsible for a significant loss of functional abilities. The mechanisms underlying loss of awareness in AD is unknown, although previous findings have implicated dysfunction of primary executive functioning (EF) or episodic memory (EM) to be the cause. Therefore, our main study objective was to explore the involvement of EF and EM dysfunction in amyloid-related loss of awareness across the clinical spectrum of AD. Methods: A total of 895 participants (362 clinically normal [CN], 422 people with mild cognitive impairment [MCI] and 111 with dementia) from the Alzheimer's Disease Neuroimaging Initiative were used for the analyses. A sub-analysis was performed in 202 participants who progressed in their clinical diagnosis from CN to MCI or MCI to dementia as well as dementia patients. Mediation models were used in each clinical group with awareness (assessed with the Everyday Cognitive function questionnaire) as a dependent variable to determine whether EF and/or EM would mediate the effect of amyloid on awareness. We also ran these analyses with subjective and informant complaints as dependent variables. Direct correlations between all variables were also performed. Results: We found evidence for a decline in awareness across the groups, with increased awareness observed in the CN group and decreased awareness observed in the MCI and dementia groups. Our results showed that EM, and not EF, partially mediated the relationship between amyloid and awareness such that greater amyloid and lower EM performance was associated with lower awareness. When analyzing each group separately, this finding was only observed in the MCI group and in the group containing progressors and dementia patients. When repeating the analyses for subjective and informant complaints separately, the results were replicated only for the informant's complaints. Discussion: Our results demonstrate that decline in EM and, to a lesser degree, EF, mediate the effect of amyloid on awareness. In line with previous studies demonstrating the development of anosognosia in the prodromal stage, our findings suggest that decreased awareness is the result of an inability for the participant to update his/her insight into his/her cognitive performance (i.e., demonstrating a petrified self).
Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.802501
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Article ; Online: Cortical microstructural imaging from diffusion MRI: towards sensitive biomarkers for clinical trials.

Rodriguez-Vieitez, Elena / Vannini, Patrizia / Montal, Victor / Graff, Caroline

Brain : a journal of neurology

2024 Volume 147, Issue 3, Page(s) 746–748

MeSH term(s)	Humans ; Alzheimer Disease ; Diffusion Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging/methods ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awae054
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Article ; Online: Measurement of Dimensions of Self-awareness of Memory Function and Their Association With Clinical Progression in Cognitively Normal Older Adults.

Mimmack, Kayden J / Gagliardi, Geoffroy P / Marshall, Gad A / Vannini, Patrizia

JAMA network open

2023 Volume 6, Issue 4, Page(s) e239964

Abstract: Importance: The ability to separately explore 2 dimensions of self-awareness of memory function-increased and decreased awareness-in cognitively normal older adults provides an important opportunity to understand subtle changes in either direction in ... ...

Abstract	Importance: The ability to separately explore 2 dimensions of self-awareness of memory function-increased and decreased awareness-in cognitively normal older adults provides an important opportunity to understand subtle changes in either direction in relation to risk of Alzheimer disease. Objective: To investigate the association of a novel measure for self-awareness of memory function with future clinical progression in individuals who were cognitively normal at baseline. Design, setting, and participants: This cohort study used data from the Alzheimer's Disease Neuroimaging Initiative, a multicenter study. Participants were older adults who were cognitively normal (ie, Clinical Dementia Rating [CDR] global score of 0) at baseline and had at least 2 years of follow-up. Data were collected from June 2010 to December 2021 and pulled from the University of Southern California Laboratory of Neuro Imaging database on January 18, 2022. Clinical progression was defined as the first instance of 2 consecutive follow-up CDR scale global scores of 0.5 or greater. Main outcomes and measures: A traditional awareness score was measured by calculating the mean discrepancy between the participant and their study partner's scores on the Everyday Cognition questionnaire. An unawareness or heightened awareness subscore was generated by capping item-level positive or negative differences at zero before averaging. The main outcome-risk of future clinical progression-was analyzed for each baseline awareness measure using Cox regression analysis. Longitudinal trajectories of each measure were additionally compared using linear mixed-effects models. Results: The 436-person sample included 232 (53.2%) female participants, with a mean (SD) age of 74.5 (6.7) years; 25 participants (5.7%) were Black, 14 (3.2%) Hispanic, and 398 (91.3%) White; and 91 participants (20.9%) clinically progressed over their period of observation. Survival analyses showed that a 1-point improvement on the unawareness subscore was associated with an 84% reduction in progression hazard (hazard ratio, 0.16 [95% CI, 0.07-0.35]; P < .001), or equivalently, a 1-point decrease was associated with a 540% increase in progression hazard (95% CI, 183% to 1347%), with no significant results for the heightened awareness or traditional scores. Conclusions and relevance: In this cohort study of 436 cognitively normal older adults, unawareness, rather than heightened awareness, of memory decline was strongly associated with future clinical progression, providing further support that discordant self- and informant-reported cognitive decline may provide important information to practitioners.
MeSH term(s)	Humans ; Female ; Aged ; Male ; Cohort Studies ; Neuropsychological Tests ; Alzheimer Disease/diagnostic imaging ; Cognitive Dysfunction ; Disease Progression
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2023.9964
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Article: Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment.

Wang, Sharon / Mimmack, Kayden / Cacciamani, Federica / Elnemais Fawzy, Michael / Munro, Catherine / Gatchel, Jennifer / Marshall, Gad A / Gagliardi, Geoffroy / Vannini, Patrizia

Frontiers in aging neuroscience

2024 Volume 16, Page(s) 1335878

Abstract: Introduction: Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and ...

Abstract	Introduction: Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross-sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI). Methods: We included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. Anosognosia was defined as the study-partner having an ECog score ≥2.5/4 and the participant having an ECog score < 2.5/4 on their baseline measure and their last observation without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia. Results: Thirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline ( Discussion: Loss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.
Language	English
Publishing date	2024-03-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2024.1335878
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Article ; Online: Multi-modal Neuroimaging Phenotyping of Mnemonic Anosognosia in the Aging Brain.

Bueichekú, Elisenda / Diez, Ibai / Gagliardi, Geoffroy / Kim, Chan-Mi / Mimmack, Kayden / Sepulcre, Jorge / Vannini, Patrizia

Communications medicine

2024 Volume 4, Issue 1, Page(s) 65

Abstract: Background: Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer's Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and ... ...

Abstract	Background: Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer's Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging. Methods: Amyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups. Results: Individuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition. Conclusions: Unawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.
Language	English
Publishing date	2024-04-05
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00497-9
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Article ; Online: Pathological correlates of impaired self-awareness of memory function in Alzheimer's disease.

Gagliardi, Geoffroy / Kuppe, Madeline / Lois, Cristina / Hanseeuw, Bernard / Vannini, Patrizia

Alzheimer's research & therapy

2021 Volume 13, Issue 1, Page(s) 118

Abstract: Introduction: Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer's disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self- ... ...

Abstract	Introduction: Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer's disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self-awareness. Methods: Two hundred thirty-six clinically normal (N) and 102 impaired (I) participants from the ADNI cohort were included. Amyloid (global) and tau burden (in entorhinal and inferior temporal cortices) were assessed using positron emission tomography (PET). Self-awareness of memory was assessed using discrepancy indexes of subjective participant-informant ratings, as well as participant-objective scores of memory performance. Subjective and objective values were derived from the Everyday Cognition memory questionnaire and Logical Memory (delayed recall). Results: Lower awareness (both methods) of memory function was associated with higher levels of pathology in the I group as compared to N. There was a significant effect of tauopathy, but not amyloidosis, on individual complaint, such that higher levels of tau associated with lower awareness. Discussion: Impaired self-awareness appears progressively in the evolution of the disease related to AD biomarkers. Discordant subjective and objective measures may be important for clinical consideration.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/diagnostic imaging ; Amyloid beta-Peptides/metabolism ; Cognitive Dysfunction ; Humans ; Positron-Emission Tomography ; Tauopathies ; Temporal Lobe/metabolism ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; tau Proteins
Language	English
Publishing date	2021-06-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-021-00856-x
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Article ; Online: Regional cerebral tau predicts decline in everyday functioning across the Alzheimer's disease spectrum.

Dubbelman, Mark A / Mimmack, Kayden J / Sprague, Emily H / Amariglio, Rebecca E / Vannini, Patrizia / Marshall, Gad A

Alzheimer's research & therapy

2023 Volume 15, Issue 1, Page(s) 120

Abstract: Background: Emerging difficulty performing cognitively complex everyday tasks, or 'instrumental activities of daily living' (IADL) may be an early clinical sign of Alzheimer's disease (AD). We aimed to investigate how changes over time in everyday ... ...

Abstract	Background: Emerging difficulty performing cognitively complex everyday tasks, or 'instrumental activities of daily living' (IADL) may be an early clinical sign of Alzheimer's disease (AD). We aimed to investigate how changes over time in everyday functioning relate to cerebral tau burden across the AD clinical spectrum. Methods: We included 581 participants (73.9 ± 7.6 years old; 52% female) from the Alzheimer's Disease Neuroimaging Initiative who underwent tau positron emission tomography (PET) and completed at least two assessments of the Functional Activities Questionnaire (FAQ). Participants were classified as cognitively normal (n = 334) or symptomatic (n = 247). We analyzed the association between longitudinal FAQ scores and baseline tau in six temporal, parietal, and frontal brain regions in mixed-effects models. Models were run in the entire sample, as well as stratified by diagnostic group (cognitively normal or symptomatic). We additionally investigated tau-PET adjusted for, as well as interacting with, amyloid-β. Results: Greater tau burden in several frontal, temporal, and parietal regions was associated with steeper decline over time in everyday functioning. These findings remained when adjusting for baseline global cortical amyloid-β; amyloid-β itself was only associated with change over time in FAQ scores when tau was not included in the model. When stratifying by diagnostic group, most associations between tau and everyday functioning, adjusted for amyloid-β, were present only in the symptomatic group. Conclusions: The rate of change in everyday functioning is related to baseline tau burden in various brain regions, more strongly so than global cortical amyloid-β, specifically in cognitively symptomatic individuals. Longitudinal studies in incident dementia populations are needed to better understand functional changes in response to AD pathology across the disease.
MeSH term(s)	Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; tau Proteins/metabolism ; Activities of Daily Living ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Positron-Emission Tomography/methods
Chemical Substances	tau Proteins ; Amyloid beta-Peptides
Language	English
Publishing date	2023-07-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-023-01267-w
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Article ; Online: Creative Connections: Computational Semantic Distance Captures Individual Creativity and Resting-State Functional Connectivity.

Orwig, William / Diez, Ibai / Vannini, Patrizia / Beaty, Roger / Sepulcre, Jorge

Journal of cognitive neuroscience

2020 Volume 33, Issue 3, Page(s) 499–509

Abstract: Recent studies of creative cognition have revealed interactions between functional brain networks involved in the generation of novel ideas; however, the neural basis of creativity is highly complex and presents a great challenge in the field of ... ...

Abstract	Recent studies of creative cognition have revealed interactions between functional brain networks involved in the generation of novel ideas; however, the neural basis of creativity is highly complex and presents a great challenge in the field of cognitive neuroscience, partly because of ambiguity around how to assess creativity. We applied a novel computational method of verbal creativity assessment-semantic distance-and performed weighted degree functional connectivity analyses to explore how individual differences in assembly of resting-state networks are associated with this objective creativity assessment. To measure creative performance, a sample of healthy adults (
MeSH term(s)	Adult ; Brain/diagnostic imaging ; Brain Mapping ; Creativity ; Humans ; Magnetic Resonance Imaging ; Semantics
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1007410-7
ISSN	1530-8898 ; 0898-929X ; 1096-8857
ISSN (online)	1530-8898
ISSN	0898-929X ; 1096-8857
DOI	10.1162/jocn_a_01658
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Article: Cortical Networks of Creative Ability Trace Gene Expression Profiles of Synaptic Plasticity in the Human Brain.

Orwig, William / Diez, Ibai / Bueichekú, Elisenda / Vannini, Patrizia / Beaty, Roger / Sepulcre, Jorge

Frontiers in human neuroscience

2021 Volume 15, Page(s) 694274

Abstract: The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain networks that support creativity by combining functional ... ...

Abstract	The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain networks that support creativity by combining functional neuroimaging data with gene expression information. Given the multifaceted nature of creative thinking, we hypothesized that distributed connectivity would not only be related to individual differences in creative ability, but also delineate the cortical distributions of genes involved in synaptic plasticity. We defined neuroimaging phenotypes using a graph theory approach that detects local and distributed network circuits, then characterized the spatial associations between functional connectivity and cortical gene expression distributions. Our findings reveal strong spatial correlations between connectivity maps and sets of genes devoted to synaptic assembly and signaling. This connectomic-transcriptome approach thus identifies gene expression profiles associated with high creative ability, linking cognitive flexibility to neural plasticity in the human brain.
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2021.694274
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