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Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association

89

A fall in hospital deaths in dementia has been interpreted as indicating an improvement in end-of-life care. Whether other indicators of quality of end-of-life care, such as emergency department (ED) attendance, show a similar trend is unclear.

Concepts: Cohort study, Clinical trial, Death, Life, Hospital

65

Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects.

Concepts: Obesity, Mass, Body mass index, Body weight, Physical science

55

In a previous study, higher concordance to the MIND diet, a hybrid Mediterranean-Dietary Approaches to Stop Hypertension diet, was associated with slower cognitive decline. In this study we related these three dietary patterns to incident Alzheimer’s disease (AD).

Concepts: Psychology, Cognition, Mind

34

One characteristic of Alzheimer’s disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells. Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-β plaques in various transgenic amyloid mouse models and in human brains with plaque pathology. The plaque-associated DCX+ cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (Iba1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX+ cells was negative for Iba1 but was highly positive for the pan-leukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells. Peculiarly, the DCX+/Iba1+ microglia and DCX+/CD8+ T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology.

Concepts: Alzheimer's disease, Immune system, Inflammation, Nervous system, Neuron, Cell, Brain, Human brain

34

Excess sugar consumption has been linked with Alzheimer’s disease (AD) pathology in animal models.

Concepts: Alzheimer's disease, Photosynthesis, Glucose, Sugar

33

Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person’s risk of developing both Alzheimer’s disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD.

Concepts: Alzheimer's disease, DNA, Death, Parkinson's disease, Apolipoprotein E, Dementia, Lewy body, Dementia with Lewy bodies

28

It is hypothesized that retrotransposons have played a fundamental role in primate evolution and that enhanced neurologic retrotransposon activity in humans may underlie the origin of higher cognitive function. As a potential consequence of this enhanced activity, it is likely that neurons are susceptible to deleterious retrotransposon pathways that can disrupt mitochondrial function. An example is observed in the TOMM40 gene, encoding a β-barrel protein critical for mitochondrial preprotein transport. Primate-specific Alu retrotransposons have repeatedly inserted into TOMM40 introns and at least one variant associated with late-onset Alzheimer’s disease originated from an Alu insertion event. We provide evidence of enriched Alu content in mitochondrial genes and postulate that Alus can disrupt mitochondrial populations in neurons, thereby setting the stage for progressive neurologic dysfunction. This Alu neurodegeneration hypothesis is compatible with decades of research and offers a plausible mechanism for the disruption of neuronal mitochondrial homeostasis, ultimately cascading into neurodegenerative disease.

Concepts: Alzheimer's disease, DNA, Gene, Mitochondrion, RNA, Neurology, Neurodegenerative disorders, Acetylcholine

28

BACKGROUND: The Alzheimer’s Disease Assessment Scale-Cognitive Behavior section (ADAS-Cog) is the most widely used measure of cognitive performance in AD clinical trials. This key role has rightly brought its performance under increased scrutiny with recent research using traditional psychometric methods, questioning the ADAS-Cog’s ability to adequately measure early-stage disease. However, given the limitations of traditional psychometric approaches, herein we use the more sophisticated Rasch Measurement Theory (RMT) methods to fully examine the strengths and weaknesses of the ADAS-Cog, and identify potential paths toward its improvement. METHODS: We analyzed AD Neuroimaging Initiative (ADNI) ADAS-Cog data (675 measurements across four time-points over 2 years) from the AD participants. RMT analysis was undertaken to examine three broad areas: adequacy of scale-to-sample targeting; degree to which, taken together, the ADAS-Cog items adequately perform as a measuring instrument; and how well the scale measured the subjects in the current sample. RESULTS: The 11 ADAS-Cog components mapped-out a measurement continuum, worked together adequately, and were stable across different time-points and samples. However, the scale did not prove to be a good match to the patient sample supporting previous research. RMT analysis also identified problematic “gaps” and “bunching” of the components across the continuum. CONCLUSION: Although the ADAS-Cog has the building blocks of a good measurement instrument, this sophisticated analysis confirms limitations with potentially serious implications for clinical trials. Importantly, and unlike traditional psychometric methods, our RMT analysis has provided important clues aimed at solving the measurement problems of the ADAS-Cog.

Concepts: Measurement, Metrology, Psychometrics, Test method, Measuring instrument

27

26

Positron emission tomography (PET) of brain amyloid β is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.

Concepts: Alzheimer's disease, Medicine, Nuclear medicine, Medical imaging, Positron emission tomography, Positron, Ethics, Morality