ANA TEREZA DI LORENZO ALHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
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- Pedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Disease(2020) CRAIG, Chesney E.; JENKINSON, Ned J.; BRITTAIN, John-Stuart; GROTHE, Michel J.; ROCHESTER, Lynn; SILVERDALE, Monty; ALHO, Ana T. D. L.; ALHO, Eduardo J. L.; HOLMES, Paul S.; RAY, Nicola J.Background There is an urgent need to identify individuals at risk of postural instability and gait difficulties, and the resulting propensity for falls, in Parkinson's disease. Objectives Given known relationships between posture and gait and degeneration of the cholinergic pedunculopontine nucleus, we investigated whether metrics of pedunculopontine nucleus microstructural integrity hold independent utility for predicting future postural instability and gait difficulties and whether they could be combined with other candidate biomarkers to improve prognostication of these symptoms. Methods We used stereotactic mapping of the pedunculopontine nucleus and diffusion tensor imaging to extract baseline pedunculopontine nucleus diffusivity metrics in 147 participants with Parkinson's disease and 65 controls enrolled in the Parkinson's Progression Markers Initiative. We also recorded known candidate markers of posture and gait changes: loss of caudate dopamine and CSF beta-amyloid 1-42 levels at baseline; as well as longitudinal progression motor symptoms over 72-months. Results Survival analyses revealed that reduced dopamine in the caudate and increased axial diffusivity in the pedunculopontine nucleus incurred independent risk of postural instability and gait difficulties. Binary logistic regression and receiver operating characteristics analysis in 117 participants with complete follow-up data at 60 months revealed that only pedunculopontine nucleus microstructure provided more accurate discriminative ability for predicting future postural instability and gait difficulties than clinical and demographic variables alone. Conclusion Dopaminergic and cholinergic loss incur independent risk for future postural instability and gait difficulties, and pedunculopontine nucleus microstructure can be used to prognosticate these symptoms from early Parkinson's disease stages. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
- Sexual Dimorphism in the Human Olfactory Bulb: Females Have More Neurons and Glial Cells than Males(2014) OLIVEIRA-PINTO, Ana V.; SANTOS, Raquel M.; COUTINHO, Renan A.; OLIVEIRA, Lays M.; SANTOS, Glaucia B.; ALHO, Ana T. L.; LEITE, Renata E. P.; FARFEL, Jose M.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; LENT, RobertoSex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55-94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-euronal cells, favoring women by 40-50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb.