scholarly journals 0422 Apocalypse Tau: The Relationship Between Inflammaging and Local Sleep Disruption in Older Adults is Mediated by Tau Burden

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A161-A162
Author(s):  
A Dave ◽  
K E Sprecher ◽  
K K Lui ◽  
M G Chappel-Farley ◽  
I Y Chen ◽  
...  

Abstract Introduction Chronic inflammation in aging is independently associated with tau burden and sleep disruption, though the mechanism linking inflammation with sleep disruption remains unknown. Recent evidence associates tau burden with deficits in local expression of sleep spindles and slow wave activity (SWA). Here we test the hypothesis that age-related central inflammation disrupts local sleep by influencing tau pathology. Methods Cognitively asymptomatic older adults from the Wisconsin Alzheimer’s Disease Research Center underwent overnight polysomnography with high-density electroencephalography (hdEEG; 256 channels) at the University of Wisconsin-Madison (n=33, 61.9±6.7 years, 23 female). EEG data were subjected to multitaper spectral analysis (0.5-40Hz) to yield topographic maps of SWA (SWA1:0.5-1Hz, SWA2:1-4.5Hz) and spindle (sigma1:11-13Hz; sigma2:13-16Hz) power during NREM sleep. Cerebrospinal fluid assay-based measurements of YKL-40 (indicating glial activation), phosphorylated tau (Ptau), and total tau (Ttau), were correlated with SWA and sigma topographical power employing Holm-Bonferroni correction. Multiple linear regression models were implemented controlling for age, apnea-hypopnea index (AHI), and sex at significant derivations. Finally, Sobel testing was employed to assess whether tau burden mediated YKL-40-sleep associations. Results Age was associated with YKL-40 (r=0.53, p=0.002), and YKL-40 was associated with both Ptau (r=0.66, p<0.001) and Ttau (r=0.68, p<0.001). Correlations between sigma2 activity and both Ptau and Ttau were detected at 14 derivations, 12 of which remained significant after controlling for age, sex, and AHI. YKL-40 was associated with sigma2 power (r=-0.39, p=0.025) across derivations expressing peak significance with tau. Sobel mediation analyses indicated that both Ptau (t=-2.15, p=0.031) and Ttau (t=-2.36, p=0.018) mediated the relationship between YKL-40 and sigma2 activity at these derivations. SWA was not associated with Ttau, Ptau, or YKL-40. Conclusion These results suggest that age-related increases in central glial activation may disrupt local expression of fast spindles by increasing tau burden, highlighting a potential role for chronic inflammation in sleep deficits observed in aging and Alzheimer’s disease. Support Supported by R56 AG052698, P50AG033514

2018 ◽  
Vol 8 (11) ◽  
pp. 83
Author(s):  
Lisa Kirk Wiese ◽  
Christine Lynn Williams

Objective: Every 66 seconds a U.S. resident develops Alzheimer’s disease (AD). Future nurses will be caring for the rapidly escalating number of adults turning 65, yet information regarding nursing students’ knowledge about the age-related disease of Alzheimer’s is limited. The purpose of this study was to examine 102 Florida baccalaureate nursing students’ basic and advanced AD knowledge.Methods: A descriptive design using two AD knowledge measures and analysis using paired samples t-test were employed.Results: Although the setting was a region of the U.S. with the highest percentage of older adults, knowledge deficits regarding age-related Alzheimer’s disease were striking. Students’ basic knowledge was significantly higher than their advanced AD knowledge (t(101) = 2.28, p = .027). Only 31% of students identified that high cholesterol may increase risk. Just 20% of students correctly answered that exercise does not prevent AD. About 25% correctly responded that the average life expectancy after the onset of AD is 6-12 years. Only 2% of nursing students correctly identified that persons with AD experience stress from disease-related symptoms. Overall, less than 50% of students correctly answered any item on the measure designed for use among health care providers.Conclusions: To better prepare nursing students to care for the increasing numbers of older adults facing risk of AD, updated curricula targeting dementia-related illnesses are essential. Information is offered regarding current state of the science resources of benefit to faculty, students, and practicing nurses, such as experiential learning and Hartford Institute of Geriatric Nursing collaborative programs.


Intelligence ◽  
2018 ◽  
Vol 70 ◽  
pp. 22-29 ◽  
Author(s):  
Karra D. Harrington ◽  
Christa Dang ◽  
Yen Ying Lim ◽  
David Ames ◽  
Simon M. Laws ◽  
...  

2018 ◽  
Author(s):  
Sarah K. Kaufman ◽  
Kelly Del Tredici ◽  
Talitha L. Thomas ◽  
Heiko Braak ◽  
Marc I. Diamond

AbstractAlzheimer’s disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological “seeds” may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/EC). The relationship of tau seeding activity, phospho-tau pathology, and progression of neurodegeneration remains obscure. Consequently, we employed an established cellular biosensor assay to quantify tau seeding activity in fixed human tissue, in parallel with AT8 phospho-tau staining of immediately adjacent sections. We studied four brain regions from each of n=247 individuals across a range of disease stages. We detected the earliest and most robust seeding activity in the TRE/EC. The LC did not uniformly exhibit seeding activity until later NFT stages. We also detected seeding activity in the first temporal gyrus and visual cortex at stages before NFTs and/or AT8-immunopositivity were detectable. AD and putative PART cases exhibited similar patterns of seeding activity that anticipated histopathology across all NFT stages. Our findings are consistent with the prion model and suggest that pathological seeding activity begins in the TRE/EC rather than in the LC, and may offer an important addition to classical histopathology.


2017 ◽  
Vol 6 (2) ◽  
pp. 22-28
Author(s):  
Dereck L. Salisbury ◽  
Fang Yu

Background: Alzheimer's disease (AD) currently affects 5.4 million Americans and is the sixth leading cause of death in the United States. The mechanism of exercise-induced brain adaptations are not fully understood, but enhanced aerobic fitness has been postulated as an essential physiological mechanism and is beginning to be studied. The purpose of this analysis was to examine the relationship between changes in aerobic fitness and cognition following 6 months of aerobic exercise training in older adults with AD. Methods: Twenty-seven community-dwelling older adults with mild to moderate AD completed a 6-month, 3 times per week, moderate-vigorous intensity cycling exercise program in 2 identical studies using a single-group repeated-measures designs. AD symptoms were measured with the AD Assessment Scale–cognitive subscale (ADAS-cog), while aerobic fitness was assessed by the intermittent shuttle walk test (ISWT) at baseline and 6 months. Pearson's correlation coefficient tests and linear regression were used to assess the relationship between changes in aerobic fitness and cognition. Results: Adjusted for age, the 6-month change in ISWT distance had an inverse relationship with the 6-month change in ADAS-Cog (r = −0.49; P = .01), indicating that enhanced aerobic fitness was associated with improved cognitive changes. Linear regression was statistically significant when adjusted by age (F([2,14] =5.33, P =.01, R2 = .31). Conclusion: Enhanced aerobic fitness may attenuate cognitive decline in persons with mild to moderate AD.


2020 ◽  
Vol 7 (1) ◽  
pp. 1-11
Author(s):  
Tammanna R. Sahrawat ◽  
Jyoti Dwivedi

Ageing is associated with a number of diseases. Alzheimer’s disease (AD) and diabetes are among such most common diseases. These two diseases are considered to be fundamentally similar disorders because they share some common elements, though they differ in the time of onset, tissues affected as well as the magnitudes of their specific traits. The present study was undertaken to prospect the association between the genes involved in Diabetes and AD; and their common pathophysiology. Using a network system biology approach, the genes common between Diabetes and AD were retrieved from DisGeNET database. The common genes were analysed using in silico tool, Cyctoscape’s various plug-ins, ClusterONE, CytoHubba, ClueGO and CluePedia. Eleven genes which can act as potential marker for both Diabetes and AD namely IL4, ICAM1, ALB, INS, CSF2, IL6, TNF, IL10, GAPDH, TLR4, and AKT have been identified in the present study. This is the first study of its kind in which relationship between Diabetes and AD has been investigated to identify their common genes, which can help in better understanding of pathophysiology of these age-related diseases.


2002 ◽  
Vol 3 (1) ◽  
pp. 12-38 ◽  
Author(s):  
Mark A. McDaniel ◽  
Steven F. Maier ◽  
Gilles O. Einstein

We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phos-phatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antiox-idants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. In sum, for most of the “brain-specific” nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.


2020 ◽  
Vol 32 (S1) ◽  
pp. 118-118
Author(s):  
Cristina G. Dumitrache ◽  
Laura Rubio ◽  
Nuria Calet ◽  
José Andrés González ◽  
Ian C. Simpson

Background:Cognitive reserve, or the extent to which brain can cope with damage, is associated with extended healthy aging and with slow age-related cognitive decline, as well as a lower number of dementia-associated clinical cognitive signs. Thus, understanding how cognitive reserve might affect different cognitive abilities is important. This study aims at investigating the associations between cognitive reserve and linguistic abilities in a group of Spanish older adults with Alzheimer’s disease.Method:The sample comprised 25 older adults with a clinical diagnostic of AD with mild to moderate dementia, and 25 controls who were residing in care homes from the province of Granada and with ages between 52 and 92 years old (M= 83.40, SD= 7.18). The Mini Mental State Examination (MMSE), the Global Deterioration Scale, the Cognitive Reserve Questionnaire, and the Short Form of the Boston Naming Test for Individuals with Aphasia were used to collect data. Correlations and regression analysis were performed.Results:Results showed that cognitive reserve positively and significantly correlated with naming and with phonological fluency but not with semantic fluency word or sentence repetitions or with the global cognitive functioning and the severity of cognitive impairment. The regression analysis showed that cognitive reserve explained 24.7% of the variance in spontaneous naming (F=3.764, p=.039). On the contrary cognitive reserve did not predict verbal fluency.Conclusions:People with higher cognitive reserve score obtained higher scores in phonological fluency and in spontaneous naming and in naming after a semantic clue. Thus, cognitive reserve is linked with better linguistic abilities in AD patients and therefore it should be considered when designing speech therapy interventions for these patients.


2020 ◽  
Vol 10 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Takayuki Tabira ◽  
Maki Hotta ◽  
Miki Murata ◽  
Kazuhiro Yoshiura ◽  
Gwanghee Han ◽  
...  

Background/Aims: Age-related changes in impairments in activities of daily living (ADL) in older adults with very mild Alzheimer’s disease (vmAD) have been scarcely explored. We clarified the characteristics of ADL impairment and examined how ADL impairments differed by age in such patients compared with community-dwelling cognitively normal older adults. Methods: The participants were 107 older adults with vmAD (Mini-Mental State Examination [MMSE] score ≥24), all of whom were first-visit outpatients at the Dementia Clinic of the Department of Neuropsychiatry, Kumamoto University Hospital. The controls were 682 community-dwelling older adults who participated in the 3rd Nakayama Study with MMSE score ≥24. We examined the association of instrumental and basic ADL (IADL and BADL, respectively) independence with the odds of vmAD using multiple logistic regression analysis and determined differences in ADL impairment by age using age- and sex-matched analysis. Results: Impairments in handling finances (OR 57.08), managing medication (OR 5.13), and dressing (OR 3.35; BADL) were associated with greater odds of vmAD. Among those aged 65 years and above, there were fewer patients with vmAD than healthy controls who could independently handle finances and medication. Among patients with vmAD, the percentages of those who could independently manage shopping, food preparation, and housekeeping only decreased after age 74. Age-related decreases in independence were observed in few BADL items; these, however, were temporary. Conclusions: Patients with vmAD show significantly decreased IADL independence from early old age.


2010 ◽  
Vol 16 (4) ◽  
pp. 672-678 ◽  
Author(s):  
MEGHAN B. MITCHELL ◽  
JERRY J. BUCCAFUSCO ◽  
ROSANN F. SCHADE ◽  
SCOTT J. WEBSTER ◽  
SHYAMALA MRUTHINTI ◽  
...  

AbstractThe immunoglobulins (IgGs) for beta amyloid (Aβ) and receptors for the advanced glycation end products (RAGE) have previously been shown to be related to memory and language measures in a mixed neurological sample of older adults. In this study, we examined group differences in Aβ and RAGE IgGs, as well as the relationship between both IgGs and cognitive performance in nondiabetic older adults with normal cognition, mild cognitive impairment (MCI), and probable Alzheimer’s disease (AD). We found RAGE and Aβ levels to be elevated in some AD participants, leading to significant AD–control group differences. While there was an overall correlation between both IgG levels and global cognition across all three groups, this relationship was largely attributable to group differences in cognition, highlighted by considerable variability within groups in the relationship between IgG levels and cognition. While findings do not support a consistent relationship between cognition and either IgG, further research with larger samples is needed to better characterize cognitive differences between AD participants with high versus low Aβ and RAGE titers. (JINS, 2010, 16, 672–678.)


Sign in / Sign up

Export Citation Format

Share Document