LUCIANA MASCARENHAS FONSECA

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LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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    ASSOCIATION BETWEEN BEREAVEMENT AND COGNITIVE DECLINE IN DOWN SYNDROME: GROUND FOR FURTHER STUDIES ON PERSISTENT COMPLEX BEREAVEMENT DISORDER AS PROPOSED BY DSM-5?
    (2015) FONSECA, L. M.; OLIVEIRA, M. C.; GUILHOTO, L. M. F. F.; CAVALHEIRO, E. A.; BOTTINO, C. M. C.
  • article 13 Citação(ões) na Scopus
    Amnestic and non-amnestic symptoms of dementia: An international study of Alzheimer's disease in people with Down's syndrome
    (2020) FONSECA, Luciana M.; PADILLA, Concepcion; JONES, Elizabeth; NEALE, Natalie; HADDAD, Glenda G.; MATTAR, Guilherme P.; BARROS, Eriton; CLARE, Isabel C. H.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.; HOEXTER, Marcelo Q.; HOLLAND, Anthony J.; ZAMAN, Shahid
    The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. Objective To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. Methods Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. Results Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). Conclusion Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.
  • article 13 Citação(ões) na Scopus
    Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome
    (2019) FONSECA, Luciana Mascarenhas; MATTAR, Guilherme Prado; HADDAD, Glenda Guerra; GONCALVES, Aline Souza; MIGUEL, Andre de Queiroz Constantino; GUILHOTO, Laura Maria; ZAMAN, Shahid; HOLLAND, Anthony J.; BOTTINO, Cassio Machado de Campos; HOEXTER, Marcelo Queiroz
    There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (>= 30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p <= 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.
  • article 0 Citação(ões) na Scopus
    Intraindividual Cognitive Variability and Magnetic Resonance Imaging in Aging American Indians: Data from the Strong Heart Study
    (2023) FONSECA, Luciana Mascarenhas; CHAYTOR, Naomi Sage; OLUFADI, Yunusa; BUCHWALD, Dedra; GALVIN, James E.; SCHMITTER-EDGECOMBE, Maureen; SUCHY-DICEY, Astrid
    Background: American Indians have high prevalence of risk factors for Alzheimer's disease and related dementias (ADRD) compared to the general population, yet dementia onset and frequency in this population are understudied. Intraindividual cognitive variability (IICV), a measure of variability in neuropsychological test performance within a person at a single timepoint, may be a novel, noninvasive biomarker of neurodegeneration and early dementia. Objective: To characterize the cross-sectional associations between IICV and hippocampal, total brain volume, and white matter disease measured by magnetic resonance imaging (MRI) among older American Indians. Methods: IICV measures for memory, executive function, and processing speed, and multidomain cognition were calculated for 746 American Indians (aged 64-95) who underwent MRI. Regression models were used to examine the associations of IICV score with hippocampal volume, total brain volume, and graded white matter disease, adjusting for age, sex, education, body mass index, intracranial volume, diabetes, stroke, hypertension, hypercholesterolemia, alcohol use, and smoking. Results: Higher memory IICV measure was associated with lower hippocampal volume (Beta = -0.076; 95%CI -0.499, -0.023; p = 0.031). After adjustment for Bonferroni or IICV mean scores in the same tests, the associations were no longer significant. No IICV measures were associated with white matter disease or total brain volume. Conclusion: These findings suggest that the IICV measures used in this research cannot be robustly associated with crosssectional neuroimaging features; nonetheless, the results encourage future studies investigating the associations between IICV and other brain regions, as well as its utility in the prediction of neurodegeneration and dementia in American Indians.
  • article 6 Citação(ões) na Scopus
    Glycemic Variability and Fluctuations in Cognitive Status in Adults With Type 1 Diabetes (GluCog): Observational Study Using Ecological Momentary Assessment of Cognition
    (2023) FONSECA, L. M.; STRONG, R. W.; SINGH, S.; BULGER, J. D.; CLEVELAND, M.; GRINSPOON, E.; JANESS, K.; JUNG, L.; MILLER, K.; PASSELL, E.; RESSLER, K.; SLIWINSKI, M. J.; VERDEJO, A.; WEINSTOCK, R. S.; GERMINE, L.; CHAYTOR, N. S.
    Background: Individuals with type 1 diabetes represent a population with important vulnerabilities to dynamic physiological, behavioral, and psychological interactions, as well as cognitive processes. Ecological momentary assessment (EMA), a methodological approach used to study intraindividual variation over time, has only recently been used to deliver cognitive assessments in daily life, and many methodological questions remain. The Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) study uses EMA to deliver cognitive and self-report measures while simultaneously collecting passive interstitial glucose in adults with type 1 diabetes. Objective: We aimed to report the results of an EMA optimization pilot and how these data were used to refine the study design of the GluCog study. An optimization pilot was designed to determine whether low-frequency EMA (3 EMAs per day) over more days or high-frequency EMA (6 EMAs per day) for fewer days would result in a better EMA completion rate and capture more hypoglycemia episodes. The secondary aim was to reduce the number of cognitive EMA tasks from 6 to 3. Methods: Baseline cognitive tasks and psychological questionnaires were completed by all the participants (N=20), followed by EMA delivery of brief cognitive and self-report measures for 15 days while wearing a blinded continuous glucose monitor. These data were coded for the presence of hypoglycemia (<70 mg/dL) within 60 minutes of each EMA. The participants were randomized into group A (n=10 for group A and B; starting with 3 EMAs per day for 10 days and then switching to 6 EMAs per day for an additional 5 days) or group B (N=10; starting with 6 EMAs per day for 5 days and then switching to 3 EMAs per day for an additional 10 days). Results: A paired samples 2-tailed t test found no significant difference in the completion rate between the 2 schedules (t17=1.16; P=.26; Cohen dz=0.27), with both schedules producing >80% EMA completion. However, more hypoglycemia episodes were captured during the schedule with the 3 EMAs per day than during the schedule with 6 EMAs per day. Conclusions: The results from this EMA optimization pilot guided key design decisions regarding the EMA frequency and study duration for the main GluCog study. The present report responds to the urgent need for systematic and detailed information on EMA study designs, particularly those using cognitive assessments coupled with physiological measures. Given the complexity of EMA studies, choosing the right instruments and assessment schedules is an important aspect of study design and subsequent data interpretation. ©Luciana Mascarenhas Fonseca, Roger W Strong, Shifali Singh, Jane D Bulger, Michael Cleveland, Elizabeth Grinspoon, Kamille Janess, Lanee Jung, Kellee Miller, Eliza Passell, Kerry Ressler, Martin John Sliwinski, Alandra Verdejo, Ruth S Weinstock, Laura Germine, Naomi S Chaytor.
  • article 21 Citação(ões) na Scopus
    Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review
    (2016) FONSECA, Luciana Mascarenhas; YOKOMIZO, Juliana Emy; BOTTINO, Cassio Machado; FUENTES, Daniel
    Background: There is a proven link between Down syndrome and the early development of the neuropathological features of Alzheimer's disease (AD). Changes in the personality and behavior of adults with Down syndrome might indicate the early stages of dementia or of frontotemporal lobar degeneration. The objective of this study was to investigate the executive functions and changes in behavior associated with frontal lobe degeneration in individuals with Down syndrome who develop AD. We conducted a systematic review selecting studies employing cognitive assessments. Summary: We identified few studies using objective measurements to determine whether cognitive aspects associated with the frontal lobe correlate with dementia in this population. We observed a tendency toward such correlations. (C) 2016 S. Karger AG, Basel
  • article 17 Citação(ões) na Scopus
    Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Tria
    (2018) SIMON, Sharon S.; HAMPSTEAD, Benjamin M.; NUCCI, Mariana P.; DURAN, Fabio L. S.; FONSECA, Luciana M.; MARTINO, Maria da Graca M.; AVILA, Renata; PORTO, Fabio H. G.; BRUCKI, Sonia M. D.; MARTINS, Camila B.; TASCONE, Lyssandra S.; JR, Edson Amaro; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.
    Background: Mnemonic strategy training (MST) has been shown to improve cognitive performance in amnestic mild cognitive impairment (a-MCI), however, several questions remain unresolved. The goal of the present study was to replicate earlier pilot study findings using a randomized controlled design and to evaluate transfer effects and changes in brain activation. Methods: Thirty patients with a-MCI were randomized into MST or education program. At baseline, participants completed clinical and neuropsychological assessments as well as structural and functional magnetic resonance imaging (fMRI). Interventions were administered individually and comprised four sessions, over 2 weeks. MST taught patients to use a three-step process to learn and recall face-name associations. Post-treatment assessment included fMRI, a separate face-name association task, neuropsychological tests, and measures of metamemory. Behavioral (i.e., non-fMRI) measures were repeated after one and 3-months. Results: Participants in the MST condition showed greater improvement on measures of face-name memory, and increased associative strategy use; effects that were accompanied by increased fMRI activation in the left anterior temporal lobe. While all participants reported greater contentment with their everyday memory following intervention, only the MST group reported significant improvements in their memory abilities. There was no clear indication of far-transfer effects to other neuropsychological tests. Conclusion: Results demonstrate that patients with a-MCI not only show stimulus specific benefits of MST, but that they appear capable of transferring training to at least some other cognitive tasks. MST also facilitated the use of brain regions that are involved in face processing, episodic and semantic memory, and social cognition, which are consonant with the cognitive processes engaged by training.
  • article 5 Citação(ões) na Scopus
    Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress
    (2021) FONSECA, Luciana Mascarenhas; MATTAR, Guilherme Prado; HADDAD, Glenda Guerra; BURDULI, Ekaterina; MCPHERSON, Sterling M.; GUILHOTO, Laura Maria de Figueiredo Ferreira; YASSUDA, Monica Sanches; BUSATTO, Geraldo Filho; BOTTINO, Cassio Machado de Campos; HOEXTER, Marcelo Queiroz; CHAYTOR, Naomi Sage
    Background: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Objective: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (>= 30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R-2 = 0.627, F(15,76) = 8.510, p < 0.001). Conclusion: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.
  • article 14 Citação(ões) na Scopus
    The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil
    (2019) FONSECA, Luciana M.; HADDAD, Glenda G.; MATTAR, Guilherme P.; OLIVEIRA, Melaine C. de; SIMON, Sharon S.; GUILHOTO, Laura M.; BUSATTO, Geraldo F.; ZAMAN, Shahid; HOLLAND, Anthony J.; HOEXTER, Marcelo Q.; BOTTINO, Cassio M.
    Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS >= 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAM DEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.
  • article 0 Citação(ões) na Scopus
    The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States
    (2023) SIMON, Sharon Sanz; BRUCKI, Sonia Maria Dozzi; FONSECA, Luciana Mascarenhas; BECKER, Jacqueline; CAPPI, Carolina; MARQUES, Andrea Horvath; HEYN, Patricia C.; GONCALVES, Priscila Dib; MARTINS, Silvia S.; BUSATTO, Geraldo; SUEMOTO, Claudia Kimie; NITRINI, Ricardo; CARAMELLI, Paulo; YASSUDA, Monica Sanches; MIOTTO, Eliane Correa; GRINBERG, Lea Tenenholz; RENTERIA, Miguel Arce; ALEGRIA, Margarita; STERN, Yaakov; RIVERA-MINDT, Monica; BERTOLA, Laiss
    Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities. It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population.Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles.Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials.Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities.