Journal of Alzheimer's Disease - Volume 70, issue 4

Authors: Jensen-Dahm, Christina | Zakarias, Johanne Købstrup | Gasse, Christiane | Waldemar, Gunhild

Article Type: Research Article

Abstract: Background: We recently reported frequent use of opioids among elderly with dementia. Discrepancies in clinical practice may in part explain the higher use of opioids in elderly with dementia, which geographical variation may be able to clarify. Objective: To investigate geographical variation in opioid use in elderly with dementia compared to elderly without dementia. Methods: Register-based cross-sectional study in the entire elderly (≥65 years) population of Denmark in 2015. Data included place of residence, prescriptions, and discharge diagnoses from hospital contacts. Prevalence of opioid use among elderly with (n  = 36,014) and without dementia (n  = 1,011,787) was …compared nationwide across the five Danish regions using logistic regression analysis and for the 98 municipalities using age and sex standardization. Results: 32.5% of elderly with dementia and 16.9% without were treated with an opioid in 2015. For home-living elderly with dementia, there was a 4-fold difference in opioid use (9.4 to 36.8%) between municipalities compared to a 1.6-fold (12.7 to 20.2%) difference for elderly without. In nursing home residents there was a 2-fold difference (dementia: 26.5 to 55.2%; no dementia: 31.8 to 60.4%). Differences between the five regions were minor. Conclusion: Opioid use in elderly with dementia was frequent and almost twice as high compared to elderly without dementia, which may challenge patient safety. The pronounced geographical variations at municipality level, particularly among elderly with dementia, indicate differences in the approach to treatment of chronic pain in primary care. Our study suggests that more guidance on treatment of pain in elderly with dementia is needed. Show more

Keywords: Analgesics, dementia, elderly, opioid, pain

DOI: 10.3233/JAD-190413

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1209-1216, 2019

Authors: El Haj, Mohamad | Boudoukha, Abdelhalim | Antoine, Pascal | Moustafa, Ahmed A. | Gallouj, Karim | Allain, Philippe

Article Type: Research Article

Abstract: We investigated, for the first time, how people with mild Alzheimer’s disease (AD) reflect on continuity of their self (i.e., whether they are the same person they were before). We invited people with mild AD and control participants to conduct The Thinking about Life Experiences (TALE) Scale. More specifically, we invited participants to indicate whether they think about their life story: when they want to feel that they are the same person that they were before (Item 1), when they are concerned about whether they are still the same type of person that they were earlier (Item 2), when they …are concerned about whether their values have changed over time (Item 3), when they are concerned about whether their beliefs have changed over time (Item 4), and when they want to understand how they have changed from who they were before (Item 5). The scores of people with AD and control participants on the items of the TALE scale were similar, except for the first item on which people with AD provided higher scores than did control participants. As demonstrated by scores on Item 1, people with mild AD can retrieve autobiographical memories to reflect on situations in which they want to feel that they are the same person that they were before. In other words, people with mild AD can draw on their personal and meaningful events to maintain a continuous sense of self or even to reflect on situations in which they are concerned about their self-continuity. Show more

Keywords: Alzheimer’s disease, autobiographical memory, self, self-continuity

DOI: 10.3233/JAD-190440

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1217-1224, 2019

Authors: Gruters, Angélique A.A. | Ramakers, Inez H.G.B. | Verhey, Frans R.J. | Köhler, Sebastian | Kessels, Roy P.C. | de Vugt, Marjolein E.

Article Type: Research Article

Abstract: Background: It is uncertain whether self- and proxy-reported cognitive decline in older adults reflect an actual objective cognitive dysfunction in the clinical sense, and if these are predictive for developing dementia. Objective: The aim of the present study is to investigate the cross-sectional and longitudinal relation between subjective cognitive decline and objective cognitive performance, depressive symptoms, and to determine the predictive value for development of dementia. Methods: We included 405 patients without dementia at first visit from the Maastricht memory clinic participating in a longitudinal cohort study. Subjective cognitive decline was measured using a self- and …proxy-report questionnaire. All patients underwent a standardized neuropsychological assessment. Follow-up assessments were performed yearly for three consecutive years, and once after five years. Results: Subjective cognitive decline was associated with lower cognitive performance and more depressive symptoms. When comparing self- (n  = 342, 84%) and proxy-reported decline (n  = 110, 27%), it was shown that proxy reports were associated with a more widespread pattern of lower cognitive performance. In participants without cognitive impairment proxy-reported decline was not associated with depressive symptoms. In contrast, self-reported decline was associated with a stable course of depressive symptoms at follow-up. Proxy-reported cognitive decline (HR = 1.76, 95% CI = 1.12– 2.78), and mutual complaints (HR = 1.73, CI:1.09– 2.76) predicted incident dementia while self-reported decline did not reach statistical significance (HR = 1.26, 95% CI = 0.65– 2.43). Conclusion: Proxy-reported cognitive decline was consistently associated with lower cognitive performance and conversion to dementia over 5 years. Self-reported cognitive decline in patients without cognitive impairment might indicate underlying depressive symptoms and thus deserve clinical attention as well. Show more

Keywords: Cognition, dementia, depressive symptoms, mild cognitive impairment, proxy-report, subjective cognitive decline

DOI: 10.3233/JAD-180857

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1225-1239, 2019

Authors: Raman, Fabio | Grandhi, Sameera | Murchison, Charles F. | Kennedy, Richard E. | Landau, Susan | Roberson, Erik D. | McConathy, Jonathan | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Tools for efficient evaluation of amyloid- and tau-PET images are needed in both clinical and research settings. Objective: This study was designed to validate a semi-automated image analysis methodology, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Methods: 127 amyloid-PET and 55 tau-PET studies with volumetric MRIs were obtained from ADNI. The BLAzER methodology utilizes segmentation of MR images by FS or NR, then visualizes and …quantifies regional brain PET data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and to detect segmentation errors. Results: BLAzER analysis required ∼5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p  < 0.001) and regional tau-PET SUVRs across all Braak staging regions (r > 0.97, p  < 0.001) with high inter-operator reproducibility (ICC > 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS versus NR segmentation with BLAzER, global SUVRs were strongly correlated for amyloid-PET (r = 0.9841, p  < 0.001), but were systematically higher (4% on average) with NR, likely due to more inclusion of white matter with NR-defined regions. Conclusions: BLAzER provides an efficient methodology for regional brain PET quantification. FDA-cleared components and visualization of registration reduce barriers between research and clinical applications. Show more

Keywords: [18F]AV-45, [18F]AV-1451, amyloid-β , brain segmentation, neuroimaging, positron emission tomography, tau

DOI: 10.3233/JAD-190329

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1241-1257, 2019

Authors: Manji, Zahra | Rojas, Asheebo | Wang, Wenyi | Dingledine, Raymond | Varvel, Nicholas H. | Ganesh, Thota

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) pathology consists of extracellular deposits of amyloid-β peptides (Aβ) and intracellular neurofibrillary tangles. These pathological alterations are accompanied by a neuroinflammatory response consisting of increased expression of inflammatory mediators. An anti-inflammatory strategy designed to prevent or delay the development of AD would benefit from knowing when neuroinflammation appears in the transgenic models during prodromal disease stages relative to Aβ pathology. We investigated the expression patterns of inflammatory mediators in the brain of 5xFAD mice in comparison to development of Aβ deposition. Expression changes in inflammatory mediators and glial markers are more robust in female mice starting at …three months of age, in contrast to males in which there is no clear trend through five months. Female and male 5xFAD mice also displayed an age-dependent increase in cortical Aβ deposition congruent with neuroinflammation. Thus, in the 5xFAD mouse model of AD, administration of an anti-inflammatory agent would be most efficacious when administered before three months of age. Show more

Keywords: Alzheimer’s disease, amyloid, chemokines, cytokines, inflammation

DOI: 10.3233/JAD-180678

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1259-1274, 2019

Authors: Calderón-Garcidueñas, Lilian | Kulesza, Randy J. | Mansour, Yusra | Aiello-Mora, Mario | Mukherjee, Partha S. | González-González, Luis Oscar

Article Type: Research Article

Abstract: A major impediment in early diagnosis of Alzheimer’s disease (AD) is the lack of robust non-invasive biomarkers of early brain dysfunction. Metropolitan Mexico City (MMC) children and young adults show hyperphosphorylated tau, amyloid-β, and α -synuclein within auditory and vestibular nuclei and marked dysmorphology in the ventral cochlear nucleus and superior olivary complex. Based on early involvement of auditory brainstem centers, we believe brainstem auditory evoked potentials can provide early AD biomarkers in MMC young residents. We measured brainstem auditory evoked potentials in MMC clinically healthy children (8.52±3.3 years) and adults (21.08±3.0 years, 42.48±8.5 years, and 71.2±6.4 years) compared to …clean air controls (6.5±0.7 years) and used multivariate analysis adjusting for age, gender, and residency. MMC children had decreased latency to wave I, delays in waves III and V, and longer latencies for interwave intervals, consistent with delayed central conduction time of brainstem neural transmission. In sharp contrast, young adults have significantly shortened interwave intervals I–III and I–V. By the 5th decade, wave V and interval I–V were significantly shorter, while the elderly cohort had significant delay in mean latencies and interwave intervals. Compensatory plasticity, increased auditory gain, cochlear synaptopathy, neuroinflammation, and AD continuum likely play a role in the evolving distinct auditory pathology in megacity urbanites. Understanding auditory central and peripheral dysfunction in the AD continuum evolving and progressing in pediatric and young adult populations may shed light on the complex mechanisms of AD development and help identify strong noninvasive biomarkers. AD evolving from childhood in air pollution environments ought to be preventable. Show more

Keywords: Air pollution, alpha synuclein, Alzheimer’s disease continuum, auditory nuclei, auditory plasticity, auditory gain, brainstem auditory evoked potentials, children, hyperphosphorylated tau, combustion and friction-derived nanoparticles

DOI: 10.3233/JAD-190405

Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1275-1286, 2019