Background This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes. Methods Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/− 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined. Results Lower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/− 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers. Conclusions Cognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.

Arthroscopic Bankart repair combined with Hill-Sachs remplissage can restore shoulder stability without significant impairment of shoulder function in patients with engaging Hill-Sachs lesions.

therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Ambipolar thin film transistors have attracted increasing research interests due to their promising applications in complementary logic circuits and the dissipative charge transporting devices. Here, we report the fabrication of an ambipolar transistor using tin mono-oxide (SnO) as a channel, which possesses balanced electron and hole field-effect mobilities. A complementary metal oxide semiconductor-like inverter using the SnO dual operation transistors is demonstrated with a maximum gain up to 30 and long-term air stability. Such logic device configuration would simplify the circuit design and fabrication process, offering more opportunities for designing and constructing oxide-based logic circuits.

No abstract

This study evaluated the utility of baseline and longitudinal MRI measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by Apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow-up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE-ε4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE-ε4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of AD.

Objective: This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).Methods: Longitudinal CSF collection and cognitive assessments were performed on a cohort of 265 participants who were cognitively normal at their baseline assessment and subsequently developed MCI or dementia. CSF b-amyloid 1-42 (Ab1-42), total tau (t-tau), and phosphorylated tau (p-tau) were determined longitudinally. Consensus diagnoses were completed annually. Cox regression analyses were performed, with baseline CSF values and time-dependent rate of change in CSF values as covariates (adjusted by baseline age, race, and education), in relation to time to onset of mild cognitive symptoms. Results:The mean time from baseline to onset of mild cognitive symptoms was 5.41 years.Increased risk of progressing from normal cognition to onset of clinical symptoms was associated with baseline values of Ab1-42, p-tau, and the ratios of p-tau/Ab1-42 and t-tau/Ab1-42 (p , 0.002). Additionally, the rate of change in the ratios of t-tau/Ab1-42 (p , 0.004) and p-tau/Ab1-42 (p , 0.02) was greater among participants who were subsequently diagnosed with MCI.Conclusions: Baseline differences in CSF values were predictive of clinical symptoms that were a harbinger of a diagnosis of MCI more than 5 years before symptom onset, and continue to show longitudinal changes as cognitive symptoms develop, demonstrating that baseline and longitudinal changes in CSF biomarkers are evident during the preclinical phase of Alzheimer disease. There is substantial evidence that a subset of older individuals who are cognitively normal have Alzheimer disease (AD) pathology in their brains, based on both autopsy findings 1-3 and amyloid imaging. [4][5][6] It has been presumed that individuals with pathologic change are at high risk of developing cognitive decline over several years, and that the earliest manifestation of this preclinical phase of disease is a change in levels of CSF biomarkers. 7The importance of CSF biomarkers was first emphasized by studies comparing patients with AD dementia with controls. 8,9 The most common finding of studies that have examined normal individuals has been that, over a follow-up duration of 1 to 8 years, baseline levels of b-amyloid 1-42 (Ab1-42) or the ratio of tau or phosphorylated tau (p-tau) to Ab1-42 is associated with an increased likelihood of being diagnosed with mild cognitive impairment (MCI). 10-12The current study addresses issues that remain unresolved by these studies. First, the outcome in all instances has been the diagnosis of MCI. Because onset of clinical symptoms can precede the diagnosis of MCI by several years, 7 it is unclear whether CSF biomarker changes are evident even earlier. Second, most subjects in previous studies were older than 70 years of age; thus, it is unknown

Arthroscopic reduction and fixation of a bony Bankart lesion can achieve good results in selected cases. The size of the reconstructed glenoid is crucial to the success of the surgery.