Increased Glucose Activity in Subgenual Anterior Cingulate and Hippocampus of High Performing Older Adults, Despite Amyloid Burden

Background: Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered. Objective: Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted. Methods: Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated. Results: The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group. Conclusion: These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

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Neural correlates of exceptional memory ability in SuperAgers: A multimodal approach using FDG-PET, PIB-PET, and MRI

10.1101/666438 ◽

2019 ◽

Author(s):

Wyllians Vendramini Borelli ◽

Eduardo Leal-Conceição ◽

Michele Alberton Andrade ◽

Nathalia Bianchini Esper ◽

Paula Kopschina Feltes ◽

...

Keyword(s):

Older Adults ◽

Cognitive Aging ◽

Fdg Pet ◽

Amyloid Deposition ◽

Cognitive Testing ◽

Anterior Cingulate ◽

Middle Aged ◽

Subgenual Anterior Cingulate Cortex ◽

Middle Aged Adults

AbstractIndividuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA). A multimodal brain analysis of SA may provide biomarkers of successful cognitive aging. Herein, a molecular (PET-FDG, PET-PIB), functional (fMRI) and structural analysis (MRI) of SA was conducted. Ten SA, ten age-matched older adults (C80) and ten cognitively normal middle-aged adults underwent cognitive testing and neuroimaging examinations. The relationship between cognitive scores and cingulate areas and hippocampus were examined. The SA group showed increased FDG SUVr in the left subgenual Anterior Cingulate Cortex (sACC, p<0.005) as compared to that in the C80 group. Amyloid deposition was similar between SA and C80 in the described regions or overall areas (p>0.05). The SA group also presented decreased connectivity between left sACC and posterior cingulate (p<0.005) as compared to that of C80 group. These results support the key role of ACC in SA, even in the presence of amyloid deposition. It also suggests that sACC can be used as a potential memory biomarker in older adults.AbbreviationsBCa – Bias corrected accelerated: SA – SuperAgers: C50 – Middle-aged controls: C80 – Age-matched controls

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Neurobiological findings associated with high cognitive performance in older adults: a systematic review

International Psychogeriatrics ◽

10.1017/s1041610218000431 ◽

2018 ◽

Vol 30 (12) ◽

pp. 1813-1825 ◽

Cited By ~ 2

Author(s):

Wyllians Vendramini Borelli ◽

Lucas Porcello Schilling ◽

Graciane Radaelli ◽

Luciana Borges Ferreira ◽

Leonardo Pisani ◽

...

Keyword(s):

Systematic Review ◽

Older Adults ◽

Cognitive Performance ◽

Anterior Cingulate ◽

Control Group ◽

High Performing ◽

High Performers ◽

Positron Emission ◽

Definition Of ◽

Molecular Brain

ABSTRACTObjectives:to perform a comprehensive literature review of studies on older adults with exceptional cognitive performance.Design:We performed a systematic review using two major databases (MEDLINE and Web of Science) from January 2002 to November 2017.Results:Quantitative analysis included nine of 4,457 studies and revealed that high-performing older adults have global preservation of the cortex, especially the anterior cingulate region, and hippocampal volumes larger than normal agers. Histological analysis of this group also exhibited decreased amyloid burden and neurofibrillary tangles compared to cognitively normal older controls. High performers that maintained memory ability after three years showed reduced amyloid positron emission tomography at baseline compared with high performers that declined. A single study on blood plasma found a set of 12 metabolites predicting memory maintenance of this group.Conclusion:Structural and molecular brain preservation of older adults with high cognitive performance may be associated with brain maintenance. The operationalized definition of high-performing older adults must be carefully addressed using appropriate age cut-off and cognitive evaluation, including memory and non-memory tests. Further studies with a longitudinal approach that include a younger control group are essential.

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Aging-Related Hypometabolism in the Anterior Cingulate Cortex of Cognitively Intact, Amyloid-Negative Seniors at Rest Mediates the Relationship between Age and Executive Function but Not Memory

Cerebral Cortex Communications ◽

10.1093/texcom/tgaa020 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

José V Pardo ◽

Shantal M Nyabwari ◽

Joel T Lee ◽

Keyword(s):

Executive Function ◽

Anterior Cingulate Cortex ◽

Cognitive Aging ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Metabolic Dysfunction ◽

Age Related ◽

Regional Specificity ◽

Cognitively Intact ◽

The Relationship

Abstract The anterior cingulate cortex (ACC) shows the most aging-related brain metabolic dysfunction that correlates with decreasing executive processing in otherwise healthy, cognitively intact volunteers. Here, data from ADNI are used to elucidate potential pathophysiological mechanisms involved in cognitive aging, that is, age-related decline in cognitive performance in the absence of known neurodegenerative disease. Amyloid-negative volunteers showed statistically significant mediation of ACC metabolism in the relationship between age and verbal fluency. A nonlinguistic task of executive function, Trails B, showed also negative correlation between performance and age, albeit weaker, but was not significant in the mediation analysis. Recall of story items, minimizing attentional demands compared with learning of word lists, did not correlate with age. ADNI subjects selected for low vascular risks also showed correlation between age and declining ACC metabolism. In the whole-brain amyloid-negative subset, ACC amyloid was not correlated with age. As expected, the metabolism in an arbitrary region such as motor cortex that was not expected to decline with cognitive aging showed no correlation with age or ACC metabolism suggesting regional specificity. These findings motivate the search for the pathophysiology of aging-related ACC dysfunction to prevent, diagnose, and treat the decline in executive function associated with cognitive aging.

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Operationalized definition of older adults with high cognitive performance

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn12-030001 ◽

2018 ◽

Vol 12 (3) ◽

pp. 221-227 ◽

Cited By ~ 5

Author(s):

Wyllians Vendramini Borelli ◽

Karoline Carvalho Carmona ◽

Adalberto Studart-Neto ◽

Ricardo Nitrini ◽

Paulo Caramelli ◽

...

Keyword(s):

Older Adults ◽

Cognitive Aging ◽

Memory Performance ◽

Developed Countries ◽

Memory Ability ◽

High Performing ◽

Aging Theory ◽

Aged Subjects ◽

Definition Of

ABSTRACT Recently, there has been an increasing number of studies on exceptional cognitive aging. Herein, we aim to objectively provide the operationalized characterization of older adults with unusually high memory ability. Some authors have defined them as “SuperAgers”, individuals aged 80 years or older with memory ability similar or superior to middle-aged subjects. On the other hand, the terminology “high-performing older adults” (HPOA) seems to appropriately conceptualize these individuals without exaggeration. A threshold for age is not a reliable criterion, but may be defined as 75 and 80 years of age for developing and developed countries, respectively. We propose that HPOA may exhibit episodic memory test scores equal to or greater than those of individuals aged 50-60 years, according to the validated tables for the respective country. This group must also have global cognition scores within expected average values for age and education. Executive functioning may play a central role in the exceptional memory performance of this group. Further studies are essential to confirm existing findings and may provide important evidence for cognitive aging theory and the neurobiology of dementia.

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Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder

BJPsych Open ◽

10.1192/bjo.2018.15 ◽

2018 ◽

Vol 4 (3) ◽

pp. 157-159 ◽

Cited By ~ 7

Author(s):

Andreas Frick ◽

Jonas Engman ◽

Kurt Wahlstedt ◽

Malin Gingnell ◽

Mats Fredrikson ◽

...

Keyword(s):

Anxiety Disorder ◽

Social Anxiety ◽

Anterior Cingulate Cortex ◽

Social Anxiety Disorder ◽

Selective Serotonin Reuptake Inhibitors ◽

Cingulate Cortex ◽

Demographic Variables ◽

Treatment Selection ◽

Anterior Cingulate ◽

Potential Biomarker

SummaryWe aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.Declaration of interestNone.

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