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1.  Early-onset dementias: diagnostic and etiological considerations 
Alzheimer's Research & Therapy  2013;5(Suppl 1):S7.
This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect.
PMCID: PMC3936399  PMID: 24565469
3.  Validation of the relevant outcome scale for Alzheimer's disease: a novel multidomain assessment for daily medical practice 
The Relevant Outcome Scale for Alzheimer's Disease (ROSA) is a new observer rating instrument recently developed for routine medical practice. The validity and reliability of ROSA as well as sensitivity to changes due to intervention were examined in an open-label, single-arm, multicenter clinical study in patients with Alzheimer's disease (AD).
The study enrolled 471 patients with a diagnosis of AD consistent with the criteria of the National Institute of Neurological and Communicative Disease and Stroke/Alzheimer's Disease and Related Disorders Association or with the Diagnostic and Statistical Manual Disorders criteria for dementia of Alzheimer's type. Following assessments of the ROSA and other standard assessments (Alzheimer's Disease Assessment Scale - cognitive subscale, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia), patients were treated with memantine for 12 weeks. Factor analysis of the baseline ROSA total scores was performed based on the principal components method using the varimax orthogonal rotational procedure. The psychometric analyses of the ROSA included internal consistency, test-retest reliability, inter-rater reliability, construct validity, and responsiveness to changes over time.
All items showed adequate factor loadings and were retained in the final ROSA as Factor 1 (all items related to cognition, communication, function, quality of life and caregiver burden) and Factor 2 (all behavior items). The ROSA demonstrated high internal consistency (Cronbach's α = 0.93), test-retest reliability (intraclass correlation coefficient = 0.93), and inter-rater reliability (intraclass correlation coefficient = 0.91). The correlation coefficients between the ROSA and each of the validated scales ranged between 0.4 and 0.7, confirming the ROSA construct validity. Nonsubstantial floor and ceiling effects were found in middle and late disease stages, whereas a small ceiling effect was observed in the early stage. The ROSA responsiveness to change was high (responsiveness index ≥0.8) for all severity stages.
The ROSA is a valid and reliable instrument to aid medical practitioners in sensitively assessing AD-relevant symptoms over time in their clinical practice.
PMCID: PMC3218804  PMID: 21914212
4.  Review of Alzheimer's disease scales: is there a need for a new multi-domain scale for therapy evaluation in medical practice? 
The present review of Alzheimer's disease (AD) rating scales aims to outline the need for a new rating scale to be used in routine clinical practice for long-term medical care of AD patients. An ideal scale would be: 1) practical, easy and quick to administer for an experienced clinician; 2) validated for AD; 3) multi-domain: covering the AD-relevant areas of cognition, activities of daily living, behavior, communication/social interaction, and quality of life; 4) applicable to all AD severity stages; 5) able to monitor disease progression; and 6) sensitive to measure therapy effects.
The National Library of Medicines' MEDLINE database was searched for the years 1981 to September 2008, using a set of keywords aiming to select instruments which cover at least some of the requirements for an ideal practical AD scale for therapy evaluation. Measures for AD staging and screening tests were not considered for review.
Of 1,902 articles resulting from the literature search, 68 relevant AD scales were identified. Most of them were scales that predominantly measure the severity of major dysfunctions in particular AD domains. Only five scales met some of the requirements for a practical multi-domain AD scale, but did not possess all required characteristics.
Despite the multitude of AD scales for various purposes, there remains a need for a new multi-domain and easy to administer AD scale for assessment of disease progression and response to therapy in daily medical practice.
PMCID: PMC2949590  PMID: 20796301

Results 1-4 (4)