Anticholinergic burden of patients with dementia attending a Psychiatry of Later Life service.

OBJECTIVES: Older adults with dementia are particularly vulnerable to adverse outcomes resulting from anticholinergic use. We aimed to: (i) Examine the anticholinergic burden of patients with dementia attending a Psychiatry of Later Life (PLL) service (ii) Examine concomitant prescription of acetylcholinesterase inhibitors (AChEIs) and anticholinergics and (iii) Compare the Anticholinergic Cognitive Burden (ACB) scale with a recently published composite list of anticholinergics. METHODS: Retrospective chart review of new referrals with a diagnosis of dementia (n = 66) seen by the PLL service, Tallaght University Hospital, Dublin, Ireland, over a consecutive period of 4 months. RESULTS: The mean ACB score was 2.2 (range = 0-9, SD = 2.1). 37.9% (n = 25) had a clinically significant ACB score (>3) and 42.1% (n = 8) of those taking AChEIs had a clinically significant ACB score. A significantly greater number of medications with anticholinergic activity were identified using the composite list versus the traditional ACB scale (2.3 v.1.5, p = 0.001). CONCLUSIONS: We demonstrated a significant anticholinergic burden amongst patients with dementia attending a specialist PLL service. There was no difference in anticholinergic burden between groups prescribed and not prescribed AChEIs, indicating that these medications are being prescribed without discontinuation of potentially inappropriate medications with anticholinergic activity. The true anticholinergic burden experienced by patients may be underestimated by the use of the ACB score alone, although the clinical significance of this finding is unclear. Calculation of true clinical anticholinergic burden load and its translation to a specific rating scale remains a challenge.

Substrate Specificity Profiling of Histone-Modifying Enzymes by Peptide Microarray.

The dynamic addition and removal of covalent posttranslational modifications (PTMs) on histone proteins serves as a major mechanism regulating chromatin-templated biological processes in eukaryotic genomes. Histone PTMs and their combinations function by directly altering the physical structure of chromatin and as rheostats for effector protein interactions. In this chapter, we detail microarray-based methods for analyzing the substrate specificity of lysine methyltransferase and demethylase enzymes on immobilized synthetic histone peptides. Consistent with the "histone code" hypothesis, we reveal a strong influence of adjacent and, surprisingly, distant histone PTMs on the ability of histone-modifying enzymes to methylate or demethylate their substrates. This platform will greatly facilitate future investigations into histone substrate specificity and mechanisms of PTM signaling that regulate the catalytic properties of histone-modifying enzymes.

The challenges of diagnosis and treatment of dementia in Down's syndrome.

OBJECTIVES: People with Down syndrome (DS) are at high risk for developing dementia and early diagnosis is vital in enhancing quality of life. Our aim was to compare our practice to consensus recommendations on evaluation, diagnosis and pharmacological treatment of individuals with DS who develop dementia. We also aimed to establish the average time taken to make a diagnosis of dementia and to commence pharmacotherapy, and to assess tolerability to acetylcholinesterase inhibitors. METHODS: Retrospective chart review in an exhaustive sample containing all current service users attending our service with DS and a diagnosis of dementia (n=20). RESULTS: The sample was 75% female and 70% had a moderate intellectual disability. The average age at diagnosis of dementia was 52.42 years old. The average time to diagnosis from first symptom was 1.13 years and the average time to commence pharmacotherapy was 0.23 years. A total of 17 patients commenced on acetylcholinesterase inhibitors, and of these seven discontinued medication due to side-effects or lack of efficacy. CONCLUSIONS: The results on anticholinesterases add to the limited pool of data on treatment of dementia in DS. There was an identified need to improve the rates of medical, vision and hearing assessments, and prospective screening. Deficiencies in screening and diagnosis may be addressed by implementing a standardised dementia assessment pathway to include prospective screening and longitudinal assessment using easily administered scales. We highlight the importance of improving the diagnostic process, as a vital window of opportunity to commence a comprehensive care plan may be lost.

Overview of the Mars Pathfinder mission and assessment of landing site predictions.

Chemical analyses returned by Mars Pathfinder indicate that some rocks may be high in silica, implying differentiated parent materials. Rounded pebbles and cobbles and a possible conglomerate suggest fluvial processes that imply liquid water in equilibrium with the atmosphere and thus a warmer and wetter past. The moment of inertia indicates a central metallic core of 1300 to 2000 kilometers in radius. Composite airborne dust particles appear magnetized by freeze-dried maghemite stain or cement that may have been leached from crustal materials by an active hydrologic cycle. Remote-sensing data at a scale of generally greater than approximately 1 kilometer and an Earth analog correctly predicted a rocky plain safe for landing and roving with a variety of rocks deposited by catastrophic floods that are relatively dust-free.