Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice.

Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

The influence of ApoE4 on the clinical outcomes and pathophysiology of degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most common cause of nontraumatic spinal cord injury in adults worldwide. Surgical decompression is generally effective in improving neurological outcomes and halting progression of myelopathic deterioration. However, a subset of patients experience suboptimal neurological outcomes. Given the emerging evidence that apolipoprotein E4 (ApoE4) allelic status influences neurodegenerative conditions, we examined whether the presence of the ApoE4 allele may account for the clinical heterogeneity of treatment outcomes in patients with DCM. Our results demonstrate that human ApoE4+ DCM patients have a significantly lower extent of improvement after decompression surgery. Functional analysis of our DCM mouse model in targeted-replacement mice expressing human ApoE4 revealed delayed gait recovery, forelimb grip strength, and hind limb mechanical sensitivity after decompression surgery, compared with their ApoE3 counterparts. This was accompanied by an exacerbated proinflammatory response resulting in higher concentrations of TNF-α, IL-6, CCL3, and CXCL9. At the site of injury, there was a significant decrease in gray matter area, an increase in the activation of microglia/macrophages, and increased astrogliosis after decompression surgery in the ApoE4 mice. Our study is the first to our knowledge to investigate the pathophysiological underpinnings of ApoE4 in DCM, which suggests a possible personalized medicine approach for the treatment of DCM in ApoE4 carriers.

Driving habits and behaviors of patients with brain tumors: a self-report, cognitive and driving simulation study.

The purpose of the study is to determine driving habits and behaviors of patients with brain tumors in order to better inform discussions around driving safety in this population. Eight-four patients with brain tumors participated in a survey on their driving behaviors since their diagnosis. Thirteen of these patients and thirteen sex- and age-matched healthy controls participated in cognitive testing and several driving simulation scenarios in order to objectively assess driving performance. Survey responses demonstrated that patients with brain tumors engage in a variety of driving scenarios with little subjectve difficulty. On the driving simulation tasks, patients and healthy controls performed similarly except that patients had more speed exceedances (U = 41, p < 0.05) and a greater variability in speed (U = 57, p < 0.05). Performance on the selective attention component of the UFOV was significantly associated with greater total errors in the Bus Following task for patients with brain tumors compared to healthy controls (rs = 0.722, p < 0.05, CI [0.080, 0.957]). Better comprehensive driving assessments are needed to identify patients with driving behaviors that put themselves and others at risk on the road.

To drive or not to drive, that is still the question: current challenges in driving recommendations for patients with brain tumours.

Driving is a complex task that requires integration of various skills that may be impaired in patients with brain tumours. Determining fitness to drive is a responsibility of all physicians in Canada; however, it is an inconsistent practice based on few objective guidelines. The primary purpose of the study is to determine the consistency of driving recommendations amongst health care professionals in Ontario. Secondary aims include evaluation of physician awareness of driving regulations and determination of whether physicians would benefit from more specific driving guidelines. An 18-item questionnaire was sent to 126 health care professionals who take care of patients with brain tumours in Ontario. Seventy-five health care professionals responded to the survey. Less than 10% said they could reliably determine fitness to drive and almost an equal percentage of respondents indicated that determining fitness to drive should be a shared responsibility. The factors deemed important in determining driving safety were highly variable; 70% indicated that cognitive and emotional deficits were important. Over a third of respondents never heard of the CMA guidelines and of those who were familiar with it, 12.5% felt they were sufficient to inform clinical decisions. 90% of respondents wanted more specific and detailed driving guidelines for patients with brain tumours. The current guidelines for physicians are not specific enough for physicians to confidently determine fitness to drive in this population. These findings suggest the need for more detailed guidelines for driving safety that are based on empirical studies on driving habits and performance in patients with a variety of brain tumours.