Social and collaborative discourse reduces the adverse effect of age on learning and memory

The adverse effects of aging on declarative memory are reliably observed when younger and older adults are compared on standard memory tests. We examined learning within a social and collaborative referential context, to determine whether this learning environment might alter the negative effects of aging. Younger pairs outperformed older pairs early in the task, but remarkably, these differences were attenuated and, on some measures, abolished by the end of the task, as older adults evidenced learning that was indistinguishable from younger adults. Learning in a social and collaborative setting may mitigate age-related cognitive decline and offers promise in memory rehabilitation

Abnormal Face‐hand Testing is Associated with Anosognosia in Patients with Neuropathologically‐confirmed Alzheimer’s Disease

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Objective To investigate whether specific elements of the neurological and neuropsychological evaluation are associated with anosognosia for memory impairment in subjects with neuropathologically-confirmed Alzheimer’s disease. Methods Included were subjects from the Arizona Study of Aging and Neurodegenerative Disease with clinically documented dementia and neuropathological confirmation of AD for whom anosognosia could be confirmed based on antemortem data. Anosognosia was defined by a discrepancy between 1) the patient’s self-report and results of testing, and/or 2) the patient’s self-report and the caregiver’s report regarding memory impairment. The anosognosic and non-anosognosic groups were compared on targeted clinical, cognitive, and neuropathological findings. Results Of 61 subjects included, 34 were diagnosed as anosognosic, and 27 non-anosognosic. The anosognosic group performed worse on two tests of frontal systems function - letter fluency (COWAT) (p=0.010) and a score derived from the Trailmaking test (Trailmaking B time – Trailmaking A time) (p=0.015). In addition, significantly more anosognosic subjects (92%) had abnormal results on face-hand testing (double simultaneous stimulation) compared to non-anosognosic subjects (62% abnormal; p=0.018). Significance In this study of patients with moderate Alzheimer’s disease (mean CDR=2), the anosognosic group showed significantly greater impairment on tests of frontal/executive function. In addition, this group had a significantly higher rate of abnormal face-hand testing, consistent with right parietal pathology. The FHT, which takes about 30 seconds to administer, may prove useful as a marker for anosognosia risk in AD.This item is part of the College of Medicine - Phoenix Scholarly Projects 2014 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]

Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome (NODRS)

The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues