The Friedman Brain Institute

Mount Sinai, NY, United States

The Friedman Brain Institute

Mount Sinai, NY, United States
SEARCH FILTERS
Time filter
Source Type

Ohm D.T.,The Friedman Brain Institute | Bloss E.B.,The Friedman Brain Institute | Janssen W.G.,The Friedman Brain Institute | Dietz K.C.,The Friedman Brain Institute | And 7 more authors.
Journal of Neuroscience | Year: 2012

Preclinical animal models have provided strong evidence that estrogen (E) therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a nonhuman primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models. © 2012 the authors.


Seto-Salvia N.,Autonomous University of Barcelona | Seto-Salvia N.,Rovira i Virgili University | Seto-Salvia N.,Institute Catala Of Paleoecologia Humana I Evolucio Social Iphes | Pagonabarraga J.,Autonomous University of Barcelona | And 25 more authors.
Movement Disorders | Year: 2012

Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia. © 2011 Movement Disorder Society.

Loading The Friedman Brain Institute collaborators
Loading The Friedman Brain Institute collaborators