Early-onset Alzheimer's disease (EOAD) is less investigated than the more common late-onset Alzheimer's disease (LOAD) despite its more aggressive course. A cortical signature of EOAD was recently proposed and may facilitate EOAD investigation. Here, we aimed to validate this proposed MRI biomarker of EOAD neurodegeneration in an Appalachian clinical cohort.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is classically characterized by alterations in memory consolidation. With the advent of diagnostic biomarkers, some patients clinically diagnosed with AD display biomarkers inconsistent with the diagnosis.
Objective: We aimed to explore differences in memory consolidation and neurodegeneration of the temporal and parietal lobes as a function of amyloid-β status in amnestic mild cognitive impairment (aMCI).
Biological clocks and other molecular biomarkers of aging are difficult to implement widely in a clinical setting. In this study, we used routinely collected hematological markers to develop an aging clock to predict blood age and determine whether the difference between predicted age and chronologic age (aging gap) is associated with advanced aging in mice. Data from 2,562 mice of both sexes and three strains were drawn from two longitudinal studies of aging.
View Article and Find Full Text PDFIntroduction: Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A-) and regional atrophy in signature areas of Alzheimer's disease (AD).
Method: Participants included 110 individuals with aMCI (A+ = 66; A- = 44) and 33 cognitively healthy participants (HP).
Background: While the cognitive hallmark of typical Alzheimer disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted.
Objective: We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group.
Methods: First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task.
Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities.
Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions.
Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD.
Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography.
View Article and Find Full Text PDFComposite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits.
View Article and Find Full Text PDFIntroduction: Agility training (AT) is used to improve neuromuscular performance and dynamic balance, which are crucial for the physical function of older adults. Activities of daily living, which decrease with age, involve tasks that simultaneously require motor, and cognitive abilities and can be considered dual tasks.
Methods: This study investigates a training program's physical and cognitive effects using an agility ladder on healthy older adults.
Brain Behav
February 2023
The causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (Aβ ) and tau proteins could directly affect WM, spreading across brain networks.
View Article and Find Full Text PDFFront Psychol
October 2022
Background: The present study compared the effects of a traditional resistance training (TRT) and resistance training combined with cognitive task (RT + CT) on body composition, physical performance, cognitive function, and plasma brain-derived neurotrophic factor (BNDF) levels in older adults.
Methods: Thirty community-dwelling older adults were randomized into TRT (70.0 ± 8.
The response to cholinesterase inhibitors (ChEIs) treatment is variable in patients with Alzheimer's disease (AD). Patients and physicians would benefit if these drugs could be targeted at those most likely to respond in a clinical setting. Therefore, this study aimed to evaluate the ability of cerebrospinal fluid (CSF) AD biomarkers, hippocampal volumes, and Default Mode Network functional connectivity to predict clinical response to ChEIs treatment in mild AD.
View Article and Find Full Text PDFObjective: We explored the associations of dual sensory impairment (DSI) with long-term depressive and anxiety symptoms as well as low perceived social support (LPSS) as a modifier of these associations.
Methods: Multinomial logistic regression models were used to examine the associations of DSI and single sensory impairment (hearing [pure-tone average > 25 dB] and vision [impaired visual acuity and/or contrast sensitivity]) with long-term depressive symptom (≥8 on the 10-item Center for Epidemiologic Studies-Depression Scale) and anxiety symptom (present on the Hopkins Symptom Checklist) latent classes from group-based trajectory models (rare/never; mild/moderate increasing; chronically high) among 2102 Health, Aging and Body Composition Study participants (mean age:74.0 ± 2.
Background: There is a dearth of studies examining the associations of objectively measured dual sensory impairment (DSI) with incident mobility and activities of daily life (ADL) difficulty longitudinally.
Methods: Cox proportional hazards models were used to examine the associations of DSI and single sensory impairment (hearing, vision) with incident mobility difficulty (many problems or inability to walk ¼ mile and/or climb 10 steps) and ADL difficulty up to six years of follow-up among 2020 participants of the Health, Aging, and Body Composition Study, a cohort of older adults aged 70-79 years from Pittsburgh, PA and Memphis, TN. Vision impairment (VI) was defined as impaired visual acuity (20/50 or worse on Bailey-Lovie distance test) and contrast sensitivity (<1.
Aging leads to profound changes in glucose homeostasis, weight, and adiposity, which are considered good predictors of health and survival in humans. Direct evidence that these age-associated metabolic alterations are recapitulated in animal models is lacking, impeding progress to develop and test interventions that delay the onset of metabolic dysfunction and promote healthy aging and longevity. We compared longitudinal trajectories, rates of change, and mortality risks of fasting blood glucose, body weight, and fat mass in mice, nonhuman primates, and humans throughout their lifespans and found similar trajectories of body weight and fat in the three species.
View Article and Find Full Text PDFWe assess the degree of phenotypic variation in a cohort of 24-month-old male C57BL/6 mice. Because murine studies often use small sample sizes, if the commonly relied upon assumption of a normal distribution of residuals is not met, it may inflate type I error rates. In this study, 3-20 mice are resampled from the empirical distributions of 376 mice to create plasmodes, an approach for computing type I error rates and power for commonly used statistical tests without assuming a normal distribution of residuals.
View Article and Find Full Text PDFRecent case studies show that the SARS-CoV-2 infectious disease, COVID-19, is associated with accelerated decline of mental health, in particular, cognition in elderly individuals, but also with neurological and neuropsychiatric illness in young people. Recent studies also show a bidirectional link between COVID-19 and mental health in that people with previous history of psychiatric illness have a higher risk for contracting COVID-19 and that COVID-19 patients display a variety of psychiatric illnesses. Risk factors and the response of the central nervous system to the virus show large overlaps with pathophysiological processes associated with Alzheimer's disease, delirium, post-operative cognitive dysfunction and acute disseminated encephalomyelitis, all characterized by cognitive impairment.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
March 2021
Aging is associated with functional and metabolic decline and is a risk factor for all noncommunicable diseases. Even though mice are routinely used for modeling human aging and aging-related conditions, no comprehensive assessment to date has been conducted on normative mouse aging. To address this gap, the Study of Longitudinal Aging in Mice (SLAM) was designed and implemented by the National Institute on Aging (NIA/NIH) as the mouse counterpart to the Baltimore Longitudinal Study of Aging (BLSA).
View Article and Find Full Text PDFObesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain.
View Article and Find Full Text PDFA female UM-HET3 mouse from the Study of Longitudinal Aging in Mice (SLAM) was euthanized at 164 weeks of age due to hind limb weakness. Necropsy and histological analysis revealed that the most probable cause of the clinical finding was the compression of the thoracolumbar segment of the spinal cord by herniated intervertebral disks. In addition, a spontaneous chordoma was incidentally found in the coccygeal bones.
View Article and Find Full Text PDFAlzheimers Dement (N Y)
August 2018
Introduction: Information about how physical exercise affects patients with amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD) is still missing. This study evaluated the impact of multicomponent exercise training on cognition and brain structure in aMCI subjects with cerebral spinal fluid positive AD biomarkers.
Methods: Forty aMCI subjects were divided in training (multicomponent exercise thrice a week for 6 months) and nontraining groups.
Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition.
View Article and Find Full Text PDFMild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer's disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD.
View Article and Find Full Text PDFBrain Connect
October 2014
There is evidence that the default mode network (DMN) functional connectivity is impaired in Alzheimer's disease (AD) and few studies also reported a decrease in DMN intrinsic activity, measured by the amplitude of low-frequency fluctuations (ALFFs). In this study, we analyzed the relationship between DMN intrinsic activity and functional connectivity, as well as their possible implications on cognition in patients with mild AD and amnestic mild cognitive impairment (aMCI) and healthy controls. In addition, we evaluated the differences both in connectivity and ALFF values between these groups.
View Article and Find Full Text PDFAim: Cognitive functions can decline with age, and interventions focusing on stimulating them may have positive results. Previous studies have shown that square-stepping exercise (SSE) has a good influence on balance, but this exercise also seems to promote cognitive stimulation. Therefore, the purpose of the present study was to analyse the effect of 16 weeks of SSE on cognitive functions in non-demented community-dwelling older people.
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