scholarly journals Sex Differences in Large Artery Stiffness: Implications for Cerebrovascular Dysfunction and Alzheimer’s Disease

2021 ◽  
Vol 2 ◽  
Author(s):  
Mackenzie N. Kehmeier ◽  
Ashley E. Walker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Impairment ◽  
Disease Progression ◽  
Large Artery ◽  
Cerebrovascular Dysfunction ◽  
Artery Stiffness ◽  
Post Menopause ◽  
The Impact

Two in every three Alzheimer’s disease diagnoses are females, calling attention to the need to understand sexual dimorphisms with aging and neurodegenerative disease progression. Dysfunction and damage to the vasculature with aging are strongly linked to Alzheimer’s disease. With aging there is an increase in stiffness of the large elastic arteries, and this stiffening is associated with cerebrovascular dysfunction and cognitive impairment. However, it is unclear how the deleterious effects of arterial stiffness may differ between females and males. While environmental, chromosomal, and sex hormone factors influence aging, there is evidence that the deficiency of estrogen post-menopause in females is a contributor to vascular aging and Alzheimer’s disease progression. The purpose of this mini review is to describe the recent developments in our understanding of sex differences in large artery stiffness, cerebrovascular dysfunction, and cognitive impairment, and their intricate relations. Furthermore, we will focus on the impact of the loss of estrogen post-menopause as a potential driving factor for these outcomes. Overall, a better understanding of how sex differences influence aging physiology is crucial to the prevention and treatment of neurodegenerative diseases.

scholarly journals Estimating Alzheimer’s Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia

2018 ◽  
Vol 15 (8) ◽  
pp. 777-788 ◽  
Author(s):  
Matthew Davis ◽  
Thomas O`Connell ◽  
Scott Johnson ◽  
Stephanie Cline ◽  
Elizabeth Merikle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Progression ◽  
Transition Probabilities ◽  
Health State ◽  
The Impact ◽  
Normal Cognition ◽  
Mci Due To Ad

Background: Alzheimer’s Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. Objective: To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. Methods: Patient-level longitudinal data from the National Alzheimer’s Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. Results: Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. Conclusion: Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.

Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer’s Disease Reveals Sex Differences

2020 ◽  
Vol 78 (4) ◽  
pp. 1707-1719
Author(s):  
Biancamaria Guarnieri ◽  
Michelangelo Maestri ◽  
Federico Cucchiara ◽  
Annalisa Lo Gerfo ◽  
Alessandro Schirru ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Health Status ◽  
Type I ◽  
Activity Trackers ◽  
Increased Risk ◽  
Wearable Activity Trackers

Background: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention. Objective: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities. Methods: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status. Results: Wake after sleep onset (WASO) was higher (p < 0.001) and sleep efficiency (SE) lower (p = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p = 0.004). SE was lower in male AD compared to female AD (p = 0.038) and SRI lower in male AD compared to male controls (p = 0.008), male MCI (p = 0.047), but also female AD subjects (p = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p = 0.009) in the overall population, controls (p = 0.005), and AD subjects (p = 0.034). The confusion-matrices showed good predictive power of actigraphic data. Conclusion: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications.

The Impact of Amyloid-β or Tau on Cognitive Change in the Presence of Severe Cerebrovascular Disease

2020 ◽  
Vol 78 (2) ◽  
pp. 573-585
Author(s):  
Hyemin Jang ◽  
Hee Jin Kim ◽  
Yeong Sim Choe ◽  
Soo-Jong Kim ◽  
Seongbeom Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Interaction Effect ◽  
Significant Interaction ◽  
Amyloid Β ◽  
Cognitive Change ◽  
Significant Interaction Effect ◽  
The Impact

Background: As Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) commonly coexist, the interaction between two has been of the considerable interest. Objective: We determined whether the association of Aβ and tau with cognitive decline differs by the presence of significant CSVD. Methods: We included 60 subcortical vascular cognitive impairment (SVCI) from Samsung Medical Center and 82 Alzheimer’s disease-related cognitive impairment (ADCI) from ADNI, who underwent Aβ (florbetaben or florbetapir) and tau (flortaucipir, FTP) PET imaging. They were retrospectively assessed for 5.0±3.9 and 5.6±1.9 years with Clinical Dementia Rating-sum of boxes (CDR-SB)/Mini-Mental State Examination (MMSE). Mixed effects models were used to investigate the interaction between Aβ/tau and group on CDR-SB/MMSE changes. Results: The frequency of Aβ positivity (45% versus 54.9%, p = 0.556) and mean global FTP SUVR (1.17±0.21 versus 1.16±0.17, p = 0.702) were not different between the two groups. We found a significant interaction effect of Aβ positivity and SVCI group on CDR-SB increase/MMSE decrease (p = 0.013/p < 0.001), and a significant interaction effect of global FTP uptake and SVCI group on CDR-SB increase/MMSE decrease (p < 0.001 and p = 0.030). Finally, the interaction effects of regional tau and group were prominent in the Braak III/IV (p = 0.001) and V/VI (p = 0.003) not in Braak I/II region (p = 0.398). Conclusion: The association between Aβ/tau and cognitive decline is stronger in SVCI than in ADCI. Therefore, our findings suggested that Aβ positivity or tau burden (particularly in the Braak III/IV or V/VI regions) and CSVD might synergistically affect cognitive decline.

scholarly journals Eigenvector alignment: assessing functional network changes in amnestic mild cognitive impairment and Alzheimer’s disease

2020 ◽  
Author(s):  
Ruaridh Clark ◽  
Niia Nikolova ◽  
William J. McGeown ◽  
Malcolm Macdonald
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Structural Changes ◽  
Amnestic Mild Cognitive Impairment ◽  
Functional Networks ◽  
Limited Information ◽  
The Impact

AbstractEigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer’s disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network’s dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain’s functional networks develop and adapt when challenged by disease processes such as AD.

scholarly journals Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Angeles Vinuesa ◽  
Carlos Pomilio ◽  
Amal Gregosa ◽  
Melisa Bentivegna ◽  
Jessica Presa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Brain Aging ◽  
Therapeutic Targets ◽  
Low Grade ◽  
Increased Risk ◽  
The Impact

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer’s disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.

scholarly journals Alzheimer's disease and sleep disturbances: a review

2019 ◽  
Vol 77 (11) ◽  
pp. 815-824 ◽  
Author(s):  
Conrado Regis Borges ◽  
Dalva Poyares ◽  
Ronaldo Piovezan ◽  
Ricardo Nitrini ◽  
Sonia Brucki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sleep Disturbances ◽  
Neurodegenerative Process ◽  
Preclinical Ad ◽  
Scientific Attention ◽  
Meta Analyses ◽  
The Impact

ABSTRACT The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD.

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