The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.     

Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10(-8); corrected P-value for equivalent number of independent quantitative traits=7.7 × 10(-8)) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10(-8); corrected P-value=1.7 × 10(-7)). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10(-6)).     

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.     

White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study

BACKGROUND AND PURPOSE: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects.MATERIALS AND METHODS: In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions.RESULTS: Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy.CONCLUSION: Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.

The corpus callosum (CC) is the most important commissural tract in the brain containing myelinated axons transversing the subcortical white matter. The CC serves to unite the 2 hemispheres anatomically and functionally, and CC atrophy may be associated with cognitive and motor deficits.^1–5 A gradual decline in the area and width of the CC has been reported after the fourth decade of life.⁶There is a considerable interindividual variability in the area and shape of the CC in the healthy elderly. Both positive and negative results have been obtained regarding the correlation of CC cross-sectional areas to factors such as sex and handedness,^7–15 number of lacunes and the presence of infarcts in the cerebral hemispheres,^16,17 and/or brain size.¹⁸The mechanism for CC atrophy is poorly understood, but CC atrophy may reflect pathologic changes in subcortical white matter, as reported in patients with multiple sclerosis¹⁹ and vascular dementia.²⁰ In healthy elderly subjects, CC atrophy may result from axonal disruption due to white matter damage.The association between age-related white matter changes (ARWMC) and CC atrophy was previously examined in 5 studies of the elderly with leukoaraiosis,²¹ infarcts and cardiovascular risk factors,¹⁶ Alzheimer disease (AD),^21–23 and healthy elderly controls.^16,21–23 Each of these studies was based on relatively small sample sizes, and taken together, they have not provided a common conclusion concerning the potential influence of ARWMC on the size of the CC. For example, in 3 studies analyzing MR imaging from patients with AD, 1 study (N = 15) found significant correlation between ARWMC and CC atrophy, whereas 2 studies (N = 21 and N = 29) did not find any significant correlation.^22,23 In healthy elderly controls, 3 ^21,22 of 4 studies (n ≤ 29)^16,21–23 found a significant correlation between ARWMC and CC atrophy. The same association was found in a population with cardiovascular risk factors (n = 14) and infarcts (n = 30).¹⁶ However, in the population of elderly subjects with leukoaraiosis (N = 62), Yamauchi et al (2000)²⁴ did not find any significant correlation between ARWMC and CC atrophy.The contradictory conclusions could be due to the use of different methods for segmentation and subdivision of the CC or to different rating techniques for assessment of ARWMC and CC. Small populations and the use of subjective rating scales may obscure potential correlations.The aim of this study was to investigate the correlation between regional ARWMC and atrophy of CC subregions in a large population of nondisabled elderly subjects with leukoaraiosis.     

Selective vulnerability of alpha motor neurons in ALS: Relation to autoantibodies toward acetylcholinesterase (AChE) in ALS patients

The degenerative process in amyotrophic lateral sclerosis (ALS) concerns primarily alpha motor neurons in the spinal cord and brain stem, and neurons forming descending pathways to the cord, especially in the pyramidal tract. Some degeneration of large peripheral sensory nerve fibers often occurs too, but preganglionic autonomie neurons and gamma motor neurons are most often spared in the disease. The vulnerability of alpha motor neurons compared to other types of neurons in ALS is discussed in relation to retrograde axoplasmic transport from peripheral blood of foreign noxious macromolecules, interneuronal transport of such molecules, and neuronal surface structure properties relevant to uptake for retrograde axoplasmic transport. Certain differences in these aspects between alpha motor neurons and other neuronal types exist. Some differences concern the neuronal turnover of acetylcholinesterase (AChE), which could be of special interest in view of the recent demonstration of regular occurrence of autoantibodies towards this enzyme in ALS patients.