Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition

Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as strongly agree or somewhat agree (68-88 across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment. Copyright © International Psychogeriatric Association 2014

99mTc Hexamethyl-Propylene-Aminoxime Single-Photon Emission Computed Tomography Prediction of Conversion From Mild Cognitive Impairment to Alzheimer Disease

Objective—To examine the utility of single photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)

DEVELOPMENT OF AN UPSA SHORT FORM FOR USE IN LONGITUDINAL STUDIES IN THE EARLY ALZHEIMER’S DISEASE SPECTRUM

BACKGROUND: In individuals with only mild or very mild cognitive attenuations (i.e., so-called pre-clinical AD), performance-based measures of function may be superior to informant-based measures because of increased sensitivity, greater reliability, and fewer ceiling effects. Objective: We sought to determine if a performance-based measure of everyday function would demonstrate adequate psychometric properties and validity in the context of serial assessment over a one-year period in patients with Mild Cognitive Impairment (MCI) and early stage Alzheimer’s disease (AD). Design: Participants were assessed with the performance-based measure at baseline, six weeks, and one year. Setting: A specialized center for the assessment and treatment of AD. Participants: Three groups of subjects participated: a healthy subjects (HS) older cognitively intact group (N=43), an MCI group (N=20), and an AD group (N=26). Measurements: A three subtest short form of the UCSD Performance-Based Skills Assessment (UPSA) (called the UPSA-3) was the measure of interest. It consisted of the Communication, Planning, and Finance subtests. Results: Mixed model repeated measures were used to assess performance over time. Large group effects were present (HS>MCI>AD). Additionally, the AD and MCI groups demonstrated declines over one year, while the HS group remained stable (group x time interaction p=.11). The MCI/AD group demonstrated adequate test-retest reliability and did not demonstrate ceiling or floor effects. Conclusion: Our data indicate that the UPSA-3 is suitable for clinical trials in that it has adequate ecological coverage and reasonable psychometric properties, and perhaps most importantly, demonstrates validity in serial assessments

Questionable Dementia: Clinical Course and Predictors of Outcome

OBJECTIVE:To evaluate the clinical course and predictors of outcome in outpatients with cognitive impairment who do not meet criteria for dementia at initial evaluation. DESIGN: Naturalistic longitudinal study. METHODS: Cognitively impaired patients in a memory disorders clinic who fell between the “normal” and “dementia” categories were defined broadly as “questionable dementia” (QD).Of 127consecutiveQ D patients, 75were followed for a minimum of 1year (mean 2.5 years, SD 1.7).Baseline neuropsychological testing was conducted in 62 of these 75 QD patients. RESULTS:: At the final follow-up time-point, 41.3% met diagnostic criteria for dementia (27 of 31 patients with dementia had possible or probable Alzheimer’s Disease, AD), 44% were rated as not demented, and 14.7% remained as “uncertain” dementia. Increased age was associated with the final diagnosis of dementia, but duration of follow-up, Clinical Dementia Rating, and modified Mini Mental State (mMMS) scores were not predictive. Low scores on the mMMS delayed recall subtest, consistent long-term retrieval on the Selective Reminding Test, category naming for animals, and the WAIS-R digit symbol, picture arrangement, and block design subtests were predictive of the final diagnosis of dementia (all P 5.01). mMMS delayed recall showed 66.7% sensitivity and 71.4% specificity, the other five neuropsychological subtests together showed 66.7% sensitivity and 66.7% specificity, and the six tests together showed 81% sensitivity and 76.9% specificity. Similar predictive accuracy was obtained for the final diagnosis of AD. CONCLUSIONS:In Q D patients, poor performance on the mMMS delayed recall item may be a useful predictor of the diagnosis of dementia (and AD) on follow-up. Combining a screening instrument like the mMMS with specific neuropsy

Predictive Utility of Type and Duration of Symptoms at Initial Presentation in Patients with Mild Cognitive Impairment

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD

Role of Amyloid-β and Tau Proteins in Alzheimer's Disease : Confuting the Amyloid Cascade

Altres ajuts: R01 AG017761/AG/NIA NIH HHS/United States; R01 AG049402/AG/NIA NIH HHS/United StatesThe "Amyloid Cascade Hypothesis" has dominated the Alzheimer's disease (AD) field in the last 25 years. It posits that the increase of amyloid-β (Aβ) is the key event in AD that triggers tau pathology followed by neuronal death and eventually, the disease. However, therapeutic approaches aimed at decreasing Aβ levels have so far failed, and tau-based clinical trials have not yet produced positive findings. This begs the question of whether the hypothesis is correct. Here we have examined literature on the role of Aβ and tau in synaptic dysfunction, memory loss, and seeding and spreading of AD, highlighting important parallelisms between the two proteins in all of these phenomena. We discuss novel findings showing binding of both Aβ and tau oligomers to amyloid-β protein precursor (AβPP), and the requirement for the presence of this protein for both Aβ and tau to enter neurons and induce abnormal synaptic function and memory. Most importantly, we propose a novel view of AD pathogenesis in which extracellular oligomers of Aβ and tau act in parallel and upstream of AβPP. Such a view will call for a reconsideration of therapeutic approaches directed against Aβ and tau, paving the way to an increased interest toward AβPP, both for understanding the pathogenesis of the disease and elaborating new therapeutic strategies