LUCIANA MASCARENHAS FONSECA
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject 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.- 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, ShahidThe 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.
- 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 QueirozThere 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.
- 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, AstridBackground: 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.
- 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, DanielBackground: 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
- 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 SageBackground: 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.
- 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.
- Screening for Dementia and Cognitive Decline in Adults With Down Syndrome A Novel Approach Using the Informant Questionnaire on Cognitive Decline in the Elderly(2022) MATTAR, Guilherme Prado; UCHIDA, Ricardo R.; HADDAD, Glenda G.; SHIOZAWA, Pedro; SILVA, Maria de Fatima Reboucas da; HOEXTER, Marcelo Q.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. de Campos; FONSECA, Luciana M.; V, Orestes ForlenzaObjective: The aim was to examine the psychometric properties of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a diagnostic tool to screen for dementia in aging individuals with Down syndrome (DS). Methods: This was a cross-sectional study of 92 individuals with DS 30 y or above of age) evaluated with the IQCODE. Using the informant questionnaire of the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, we divided the subjects into 3 diagnostic groups: stable cognition; prodromal dementia; and dementia. The ability of the IQCODE to discriminate between diagnostic groups was analyzed by calculating the areas under the receiver operator characteristic curves (AUCs). Results: The optimal IQCODE cutoffs were 3.14 for dementia versus stable cognition (AUC= 0.993; P< 0.001) and 3.11 for prodromal dementia+dementia versus stable cognition (AUC= 0.975; P< 0.001), with sensitivity/specificity/accuracy of 100%/96.8%/97.3%, and 93.3%/ 91.9%/92.4%, respectively. The IQCODE showed a weak-to-moderate correlation with cognitive performance (P< 0.05). Conclusion: The IQCODE is a useful tool to screen for cognitive decline in individuals with DS and is suitable for use in a primary care setting.
- MoCA Intraindividual Cognitive Variability in Older Adults With Type 1 Diabetes(2023) FONSECA, Luciana Mascarenhas; SHEPPARD, David P.; CHAYTOR, Naomi S.Older adults with type 1 diabetes (T1D) may have an elevated risk of developing Alzheimer disease and related dementia. Higher intraindividual cognitive variability (IICV) has been proposed as a novel risk factor of Alzheimer disease and related dementia. Here, we examined the association between cross-domain IICV measured using the Montreal Cognitive Assessment (MoCA) and cognitive impairment measured using traditional neuropsychological tests in older individuals with T1D. Participants with T1D (N=201) completed both the MoCA and a battery of traditional neuropsychological tests. Participants with cognitive impairment, determined using traditional tests, had significantly higher IICV scores and significantly lower total MoCA scores (P<0.001). However, the effect of the total score was greater than that of the IICV score on the likelihood of cognitive impairment (total odds ratio=3.50, IICV odds ratio=2.03, P<0.001). The MoCA total score performed better than the MoCA IICV score in identifying T1D individuals classified with cognitive impairment.
- Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome(2018) NEALE, Natalie; PADILLA, Concepcion; FONSECA, Luciana Mascarenhas; HOLLAND, Tony; ZAMAN, ShahidPeople with Down syndrome (DS) develop Alzheimer's disease (AD) at higher rates and a younger age of onset compared to the general population. As the average lifespan of people with DS is increasing, AD is becoming an important health concern in this group. Neuroimaging is becoming an increasingly useful tool in understanding the pathogenesis of dementia development in relation to clinical symptoms. Furthermore, neuroimaging has the potential to play a role in AD diagnosis and monitoring of therapeutics. This review describes major recent findings from in vivo neuroimaging studies analysing DS and AD via ligand-based positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG)-PET, structural magnetic resonance imaging (sMRI), and diffusion tensor imaging (DTI). Electroencephalography (EEG) and retinal imaging are also discussed as emerging modalities. The review is organized by neuroimaging method and assesses the relationship between cognitive decline and neuroimaging changes. We find that amyloid accumulation seen on PET occurs prior to dementia onset, possibly as a precursor to the atrophy and white matter changes seen in MRI studies. Future PET studies relating tau distribution to clinical symptoms will provide further insight into the role this protein plays in dementia development. Brain activity changes demonstrated by EEG and metabolic changes seen via FDG-PET may also follow predictable patterns that can help track dementia progression. Finally, newer approaches such as retinal imaging will hopefully overcome some of the limitations of neuroimaging and allow for detection of dementia at an earlier stage.