Impaired survival of neural progenitor cells in dentate gyrus of adult mice lacking fMRP.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability in humans. Individuals affected with the disorder exhibit a deficiency of the fragile X mental retardation protein (FMRP), due to transcriptional silencing of the Fmr1 gene. It is widely accepted that learning deficits in FXS result from impaired synaptic function and/or plasticity in the brain. Interestingly, recent evidence suggests that conditional knockout of Fmr1 in neural progenitor cells in mice impairs hippocampal neurogenesis, which in turn contributes to learning impairments. To examine the nature of the neurogenic impairments and determine whether they impact the morphology of the dentate gyrus, we assessed the extent of neural progenitor cell proliferation, survival, and differentiation in older adult Fmr1 knockout mice. Here, we show that the number of fast-proliferating cells in the subgranular layer of the dentate gyrus, as well as the subsequent survival of these cells, are dramatically reduced in Fmr1 knockout mice. In addition, the number of mature neurons in the granule layer of the dentate gyrus of these mice is significantly smaller than in wild type littermate controls, suggesting that impaired proliferation and survival of neural progenitor cells compromises the structure of the dentate gyrus. Impaired adult neurogenesis may underlie, at least in part, the learning deficits that characterize fragile X syndrome.

Cognitive impairment in patients with advanced heart failure and its implications on decision-making capacity.

Cognitive impairment (CI) is a multifaceted entity that entails more than just memory loss. Deficits in other domains, most importantly executive function, can have profound effects on health outcomes in afflicted patients. The prevalence of CI among the heart failure population is exceedingly high, and even higher so among patients with advanced heart failure (AHF). These patients display consistent declines in memory, attention, psychomotor abilities, and executive function. Such deficits interfere with patients' abilities to recognize worsening symptoms, adhere to complex medication regimens, and make sound decisions pertaining to medical care. Regular evaluation of cognitive status using instruments such as the Montreal Cognitive Assessment is a fast, reliable method that allows physicians who treat patients with AHF to anticipate these obstacles to treatment and act accordingly. Referral for more comprehensive neuropsychological evaluation should be considered for patients with unexplained declines from baseline, legal determination of competence, and for heart transplant or ventricular assist device placement candidates.