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Levetiracetam effects on hippocampal blood flow and symptoms in medication-free individuals with nonaffective first episode psychosis (letter) [Letter]

Goff, Donald C; Santacatterina, Michele; Capichioni, Gillian; Ando, Fumika; Hart, Kamber; Convit, Antonio; Rusinek, Henry
PMID: 37657280
ISSN: 1573-2509
CID: 5618122

Paediatric obesity and metabolic syndrome associations with cognition and the brain in youth: Current evidence and future directions

Sadler, Jennifer R; Thapaliya, Gita; Ranganath, Kushi; Gabay, Andrea; Chen, Liuyi; Smith, Kimberly R; Osorio, Ricardo S; Convit, Antonio; Carnell, Susan
Obesity and components of the metabolic syndrome (MetS) are associated with differences in brain structure and function and in general and food-related cognition in adults. Here, we review evidence for similar phenomena in children and adolescents, with a focus on the implications of extant research for possible underlying mechanisms and potential interventions for obesity and MetS in youth. Current evidence is limited by a relative reliance on small cross-sectional studies. However, we find that youth with obesity and MetS or MetS components show differences in brain structure, including alterations in grey matter volume and cortical thickness across brain regions subserving reward, cognitive control and other functions, as well as in white matter integrity and volume. Children with obesity and MetS components also show some evidence for hyperresponsivity of food reward regions and hyporesponsivity of cognitive control circuits during food-related tasks, altered brain responses to food tastes, and altered resting-state connectivity including between cognitive control and reward processing networks. Potential mechanisms for these findings include neuroinflammation, impaired vascular reactivity, and effects of diet and obesity on myelination and dopamine function. Future observational research using longitudinal measures, improved sampling strategies and study designs, and rigorous statistical methods, promises to further illuminate dynamic relationships and causal mechanisms. Intervention studies targeted at modifiable biological and behavioural factors associated with paediatric obesity and MetS can further inform mechanisms, as well as test whether brain and behaviour can be altered for beneficial outcomes.
PMID: 37202148
ISSN: 2047-6310
CID: 5508112

Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study

Ramos-Cejudo, Jaime; Johnson, Andrew D; Beiser, Alexa; Seshadri, Sudha; Salinas, Joel; Berger, Jeffrey S; Fillmore, Nathanael R; Do, Nhan; Zheng, Chunlei; Kovbasyuk, Zanetta; Ardekani, Babak A; Nunzio, Pomara; Bubu, Omonigho M; Parekh, Ankit; Convit, Antonio; Betensky, Rebecca A; Wisniewski, Thomas M; Osorio, Ricardo S
Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.
PMID: 35470685
ISSN: 2047-9980
CID: 5215632

Does obesity-associated insulin resistance affect brain structure and function of adolescents differentially by sex?

Gabay, Andrea; London, Stephanie; Yates, Kathy F; Convit, Antonio
Metabolic abnormalities affect the adolescent brain. For equivalent abnormalities in metabolism young people exhibit deficits in more cognitive domains than adults. We examine sex differences performance for adolescents with obesity/insulin resistance (IR) and evaluated how sex and IR effected frontal lobe structures and executive functioning. 125 adolescents underwent medical, cognitive, and brain-imaging assessments. Participants were categorized as insulin sensitive (IS) (QUICKI ≥ 0.350) or IR (QUICKI < 0.350). Degree of IR may affect brain and cognition differentially by sex. Females had positive associations between QUICKI and anterior cingulate cortex (ACC) volume, medial orbito-frontal cortex (OFC) thickness, and scores on the Stroop and Digit Symbol Substitution (DSST) tests. Females with IR tended to have thinner insular cortices. No such associations were found in males. In female adolescents, IR may negatively affect brain structure and function. No such effects were found for males. Although needing more development, hormonal effects and inflammation are potential contributors.
PMID: 34875560
ISSN: 1872-7506
CID: 5099582

Lower extremity MRI following 10-week supervised exercise intervention in patients with diabetic peripheral neuropathy

Brown, Ryan; Sharafi, Azadeh; Slade, Jill M; Convit, Antonio; Davis, Nathan; Baete, Steven; Milton, Heather; Mroczek, Kenneth J; Kluding, Patricia M; Regatte, Ravinder R; Parasoglou, Prodromos; Rao, Smita
INTRODUCTION/BACKGROUND:The purpose of this study was to characterize using MRI the effects of a 10-week supervised exercise program on lower extremity skeletal muscle composition, nerve microarchitecture, and metabolic function in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS/METHODS:) and once following intervention to measure relaxation times (T1, T1ρ, and T2), phosphocreatine recovery, fat fraction, and diffusion parameters. RESULTS:and postintervention MRI metrics were: calf adipose infiltration -2.6%±6.4%, GM T1ρ -4.1%±7.7%, GM T2 -3.5%±6.4%, and gastrocnemius lateral T2 -4.6±7.4%. Insignificant changes were observed in gastrocnemius phosphocreatine recovery rate constant (p>0.3) and tibial nerve fractional anisotropy (p>0.6) and apparent diffusion coefficient (p>0.4). CONCLUSIONS:The 10-week supervised exercise intervention program successfully reduced adiposity and altered resting tissue properties in the lower leg in DPN. Gastrocnemius mitochondrial oxidative capacity and tibial nerve microarchitecture changes were not observed, either due to lack of response to therapy or to lack of measurement sensitivity.
PMID: 34518157
ISSN: 2052-4897
CID: 5012272

The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study

Ramos-Cejudo, Jaime; Johnson, Andrew D; Beiser, Alexa; Seshadri, Sudha; Salinas, Joel; Berger, Jeffrey S; Fillmore, Nathanael R; Do, Nhan; Zheng, Chunlei; Kovbasyuk, Zanetta; Ardekani, Babak A; Bubu, Omonigho M; Parekh, Ankit; Convit, Antonio; Betensky, Rebecca A; Wisniewski, Thomas M; Osorio, Ricardo S
PMID: 34916927
ISSN: 1663-4365
CID: 5080232

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Pegueroles, Jordi; Pané, Adriana; Vilaplana, Eduard; Montal, Víctor; Bejanin, Alexandre; Videla, Laura; Carmona-Iragui, María; Barroeta, Isabel; Ibarzabal, Ainitze; Casajoana, Anna; Alcolea, Daniel; Valldeneu, Silvia; Altuna, Miren; de Hollanda, Ana; Vidal, Josep; Ortega, Emilio; Osorio, Ricardo; Convit, Antonio; Blesa, Rafael; Lleó, Alberto; Fortea, Juan; Jiménez, Amanda
Aims/hypothesis/UNASSIGNED:Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. Methods/UNASSIGNED:We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). Results/UNASSIGNED:). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE] <0.05), but not to AD CSF biomarkers. It is notable that the impact of obesity on brain metabolism and structure was also found in amyloid negative individuals. Conclusions/interpretation/UNASSIGNED:In the cognitively unimpaired elderly, obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology.
PMID: 32743041
ISSN: 2352-8729
CID: 4793322

Multinuclear MR imaging in diabetic peripheral neuropathy [Meeting Abstract]

Parasoglou, Prodromos; Baete, Steven; Ho, Amanda; Brown, Ryan; Convit, Antonio; Garwood, Elisabeth; Mroczek, Kenneth; Slade, Jill
ISSN: 1085-9489
CID: 3557752


Rivas, J.; Sharma, R.; Miller, M. D.; Godinho, A.; Ayappa, I; Jean-Louis, G.; Varga, A. W.; Convit, A.; Osorio, R. S.
ISSN: 1550-9109
CID: 3114292

Cognitive functions among predominantly minority urban adolescents with metabolic syndrome

Mangone, Alexander; Yates, Kathy F; Sweat, Victoria; Joseph, Adriana; Convit, Antonio
The rise in the rate of adolescent obesity has led to a concurrent rise in the rate of metabolic syndrome (MetS) among young people. In addition to diabetes and cardiovascular disease, MetS has also been linked to cognitive dysfunction. The goal of this study was to assess whether cognitive differences exist between minority urban adolescents carrying excess weight who meet criteria for MetS as compared to their peers without MetS. Two hundred and ninety-six urban adolescents, predominantly Hispanic and carrying excess weight as defined by a BMI above 25 kg/m2, were screened for MetS and divided into MetS and no MetS groups. All participants completed the CNS Vital Signs (CNS-VS) computerized neurocognitive battery that assesses cognitive domains of Memory, Processing Speed, Reaction Time, Executive Function, Complex Attention, and Cognitive Flexibility. The MetS group (29.2%, n = 84) performed significantly lower on 2 of the 7 cognitive domains: Executive Function (EF) and Cognitive Flexibility. Additionally, waist circumference was determined to be a significant predictor of both these domains. These findings suggest EF is negatively impacted in adolescents with MetS, despite there being no statistical differences between MetS groups on most other measured cognitive domains. Due to the interrelated nature of obesity, waist circumference, and MetS, these findings have larger implications for the obesity epidemic as well.
PMID: 28631969
ISSN: 2162-2973
CID: 2604252