Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample.

Objective: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old).

Method: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures.

Discrepancies between crystallized and fluid ability are associated with frequency of social and physical engagement in community dwelling older adults.

Objective: Age differences have been noted in the discrepancies between crystallized and fluid ability (Gc-Gf). Larger Gc-Gf discrepancies have also been shown to be associated with Alzheimer's disease biomarkers and clinical severity. However, little is known regarding the relationship between Gc-Gf discrepancies in normal aging and functional outcomes.

The Historical Progression From ADL Scrutiny to IADL to Advanced ADL: Assessing Functional Status in the Earliest Stages of Dementia.

Background: Decrements in instrumental activities (IADL) have been observed in the prodromal phase of dementia. Given the long predementia stage in neurodegenerative diseases, it has been proposed that subtle functional changes may precede clinical IADL impairment. Incorporating more challenging advanced ADLs (eg, volunteer work) into the assessment process may increase the sensitivity of functional measures, thus expanding the window for monitoring or interventions.

Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial.

Importance: Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed.

Objective: To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program.

Design, Setting, And Participants: A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials.

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS).

Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT).

Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months.

Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most frequently occurring histological subtypes of breast cancer, accounting for 80-90% and 10-15% of the total cases, respectively. At the time of diagnosis and surgical resection of the primary tumour, most patients do not have clinical signs of metastases, but bone micrometastases may already be present. Our aim was to develop a novel preclinical ILC model of spontaneous bone micrometastasis.

A pooled analysis of two phase 3 clinical trials of dalfampridine in patients with multiple sclerosis.

Background: Two phase 3 clinical trials demonstrated that dalfampridine extended-release 10-mg tablets (D-ER), twice daily, significantly improved walking relative to placebo in patients with multiple sclerosis (MS). The objective of this study was to evaluate the efficacy and safety of D-ER in patients with MS using pooled data from the two phase 3 trials.

Methods: Data were pooled from the two trials, and D-ER was compared with placebo for timed-walk responder rate, changes in walking speed, and the 12-item Multiple Sclerosis Walking Scale (MSWS-12).

Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis.

Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine-ER, an extended-release formulation of dalfampridine (also known by its chemical name, 4-aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine-ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination.

Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment.

Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV + patients scanned with whole-brain MRI at 1.

Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study.

HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤ 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI).

Marked heterogeneity in growth characteristics of myoblast clonal cultures and myoblast mixed cultures obtained from the same individual.

Background: Sarcopenia is defined as an age-related decrease in skeletal muscle mass and function while adjacent satellite cells are unable to compensate for this loss. However, myoblast cultures can be established even in the presence of sarcopenia.

Objective: It is yet unknown whether satellite cells from failing muscle in older age are equally affected, as human satellite cells have been assessed using myoblast mixed cultures and not by using myoblast clonal cultures.

A phase 3 trial of extended release oral dalfampridine in multiple sclerosis.

Objective: A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics.

Methods: This was a 39-center, double-blind trial in patients with definite MS of any course type.

Differential functional magnetic resonance imaging response to food pictures in successful weight-loss maintainers relative to normal-weight and obese controls.

Background: Prior research indicates that successful weight-loss maintainers (SWLs) work harder than people of normal weight to maintain their weight loss, including greater dietary restriction of fat and higher physical activity levels. However, little work to date has examined how SWLs differ biologically from normal-weight (NW) and obese controls.

Objective: The objective was to compare the brain responses of SWLs to food pictures with those of NW and obese controls.