GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer's Disease.

Prevention of Alzheimer's disease (AD) is a high priority mission while searching for a disease modifying therapy for AD, a devastating major public health crisis. Clinical observations have identified a prodromal stage of AD for which the patients have mild cognitive impairment (MCI) though do not yet meet AD diagnostic criteria. As an identifiable transitional stage before the onset of AD, MCI should become the high priority target for AD prevention, assuming successful prevention of MCI and/or its conversion to AD also prevents the subsequent AD.

Mitochondrial Membrane Potential Influences Amyloid-β Protein Precursor Localization and Amyloid-β Secretion.

Background: Amyloid-β (Aβ), which derives from the amyloid-β protein precursor (AβPP), forms plaques and serves as a fluid biomarker in Alzheimer's disease (AD). How Aβ forms from AβPP is known, but questions relating to AβPP and Aβ biology remain unanswered. AD patients show mitochondrial dysfunction, and an Aβ/AβPP mitochondria relationship exists.

Correlation of Skin Carotenoid Content with 3-Day Dietary Intake in Community Dwelling Older Adults.

Pressure-mediated reflection spectroscopy (RS) measures skin carotenoid content (SCC). Continued validation of this method is pertinent to validate its use as an objective measure of fruit and vegetable intake. This study aimed to assess relationships between SCC scores and self-reported dietary carotenoid intake from 3-day food records in community dwelling older adults.

Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle.

Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study (   = 50) compared muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH;  = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI;   = 11) or MCI taking the ad medication donepezil (MCI + med;   = 15).

High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease.

To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid. This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City. Among all participants ( = 102), higher daily intake of the HGDiet pattern (β = 0.

Alzheimer's disease clinical trial update 2019-2021.

The current clinical trial landscape targeting Alzheimer's disease (AD) is reviewed in the context of studies completed from 2019 to 2021. This review focuses on available data for observational and phase II/III clinical trial results, which will have the most impact on the field. ClinicalTrials.

Mitochondrial pathway polygenic risk scores are associated with Alzheimer's Disease.

Genetic, animal and epidemiological studies involving biomolecular and clinical endophenotypes implicate mitochondrial dysfunction in Alzheimer's disease (AD) pathogenesis. Polygenic risk scores (PRS) provide a novel approach to assess biological pathway-associated disease risk by combining the effects of variation at multiple, functionally related genes. We investigated the associations of PRS for genes involved in 12 mitochondrial pathways (pathway-PRS) with AD in 854 participants from Alzheimer's Disease Neuroimaging Initiative.

Mutations in the Amyloid-β Protein Precursor Reduce Mitochondrial Function and Alter Gene Expression Independent of 42-Residue Amyloid-β Peptide.

Background: Dominant missense mutations in the amyloid-β protein precursor (AβPP) cause early-onset familial Alzheimer's disease (FAD) and are associated with changes in the production or properties of the amyloid-β peptide (Aβ), particularly of the 42-residue variant (Aβ42) that deposits in the Alzheimer's disease (AD) brain. Recent findings, however, show that FAD mutations in AβPP also lead to increased production of longer Aβ variants of 45-49 residues in length.

Objective: We aimed to test neurotoxicity of Aβ42 vis-á-vis longer variants, focusing specifically on mitochondrial function, as dysfunctional mitochondria are implicated in the pathogenesis of AD.

CONSENSUS: a Shiny application of dementia evaluation and reporting for the KU ADC longitudinal Clinical Cohort database.

Background: The University of Kansas Alzheimer's Disease Center (KU ADC) maintains several large databases to track participant recruitment, enrollment, and capture various research-related activities. It is challenging to manage and coordinate all the research-related activities. One of the crucial activities involves generating a consensus diagnosis and communicating with participants and their primary care providers.

Mild cognitive impairment: when nutrition helps brain energy rescue-a report from the EuGMS 2020 Congress.

Background: Mild cognitive impairment (MCI) is characterized by a decline in cognition and mainly affects older individuals above the age of 60. The global incidence of MCI varies, but it is often underdiagnosed and untreated. There is a distinct lack of approved pharmacologic options to treat MCI.

A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise.

Exercise likely has numerous benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined. If the brain does benefit from exercise it does so primarily through cumulative brief, "acute" exposures over a lifetime.

The impact of COVID-19 on the well-being and cognition of older adults living in the United States and Latin America.

Background: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru.

Methods: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020.

Bioenergetic and inflammatory systemic phenotypes in Alzheimer's disease APOE ε4-carriers.

We examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean platelet mitochondrial cytochrome oxidase Vmax activity was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. Proteins that mediate mitophagy and energy sensing were higher in APOE ε4 lymphocytes which could represent compensatory changes and recapitulate phenomena observed in post-mortem AD brains.

Apolipoprotein E4 Moderates the Association Between Vascular Risk Factors and Brain Pathology.

Background: The strongest genetic risk factor for late-onset Alzheimer disease (AD), Apolipoprotein E4 (APOE4), increases cardiovascular disease risk and may also act synergistically with vascular risk factors to contribute to AD pathogenesis. Here, we assess the interaction between APOE4 and vascular risk on cerebrovascular dysfunction and brain pathology.

Methods: This is an observational study of cognitively normal older adults, which included positron emission tomography imaging and vascular risk factors.

A ketogenic diet differentially affects neuron and astrocyte transcription.

Ketogenic diets (KDs) alter brain metabolism. Multiple mechanisms may account for their effects, and different brain regions may variably respond. Here, we considered how a KD affects brain neuron and astrocyte transcription.

Aerobic exercise improves hippocampal blood flow for hypertensive Apolipoprotein E4 carriers.

Cerebrovascular dysfunction likely contributes causally to Alzheimer's disease (AD). The strongest genetic risk factor for late-onset AD, (), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for carriers.

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer's: A 1-year randomized controlled trial.

Background: Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer's-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging.

Methods And Findings: This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs.

Mitophagy and the Brain.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis.

Psychometric Properties of NASA-TLX and Index of Cognitive Activity as Measures of Cognitive Workload in Older Adults.

Cognitive workload is increasingly recognized as an important determinant of performance in cognitive tests and daily life activities. Cognitive workload is a measure of physical and mental effort allocation to a task, which can be determined through self-report or physiological measures. However, the reliability and validity of these measures have not been established in older adults with a wide range of cognitive ability.

Reliability of P3 Event-Related Potential During Working Memory Across the Spectrum of Cognitive Aging.

Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals with a vast range of cognitive ability has not been established. In this test-retest reliability study, 39 older individuals (age 74.

Effects of high intensity interval exercise on cerebrovascular function: A systematic review.

High intensity interval exercise (HIIE) improves aerobic fitness with decreased exercise time compared to moderate continuous exercise. A gap in knowledge exists regarding the effects of HIIE on cerebrovascular function such as cerebral blood velocity and autoregulation. The objective of this systematic review was to ascertain the effect of HIIE on cerebrovascular function in healthy individuals.

Cardiovascular disease risk is associated with middle cerebral artery blood flow velocity in older adults.

Purpose: The aim of this study was to evaluate the of cardiovascular disease (CVD) on middle cerebral blood flow velocity (MCAv) at rest and during exercise. A secondary aim was to explore the relationship between MCAv and 1) the presence of white matter lesions and 2) cognitive function.

Methods: We recruited individuals who were cognitively normal older adults.