scholarly journals Interactions between sleep disturbances and Alzheimer’s disease on brain function: a preliminary study combining the static and dynamic functional MRI

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaicheng Li ◽  
Xiao Luo ◽  
Qingze Zeng ◽  
Yerfan Jiaerken ◽  
Shuyue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Sleep Disturbance ◽  
Brain Function ◽  
Sleep Disturbances ◽  
Brain Activity ◽  
Vascular Risk Factor ◽  
Underlying Mechanism ◽  
Amyloid Pet

AbstractThough sleep disturbance constitutes the risk factor for Alzheimer’s disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.

scholarly journals Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer’s Disease

2019 ◽  
Vol 20 (4) ◽  
pp. 803 ◽  
Author(s):  
Eiko Minakawa ◽  
Keiji Wada ◽  
Yoshitaka Nagai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Sleep Disturbance ◽  
Experimental Studies ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Common Symptom ◽  
Increased Risk ◽  
Impaired Sleep

Sleep disturbance is a common symptom in patients with various neurodegenerative diseases, including Alzheimer’s disease (AD), and it can manifest in the early stages of the disease. Impaired sleep in patients with AD has been attributed to AD pathology that affects brain regions regulating the sleep–wake or circadian rhythm. However, recent epidemiological and experimental studies have demonstrated an association between impaired sleep and an increased risk of AD. These studies have led to the idea of a bidirectional relationship between AD and impaired sleep; in addition to the conventional concept that impaired sleep is a consequence of AD pathology, various evidence strongly suggests that impaired sleep is a risk factor for the initiation and progression of AD. Despite this recent progress, much remains to be elucidated in order to establish the benefit of therapeutic interventions against impaired sleep to prevent or alleviate the disease course of AD. In this review, we provide an overview of previous studies that have linked AD and sleep. We then highlight the studies that have tested the causal relationship between impaired sleep and AD and will discuss the molecular and cellular mechanisms underlying this link. We also propose future works that will aid the development of a novel disease-modifying therapy and prevention of AD via targeting impaired sleep through non-pharmacological and pharmacological interventions.

scholarly journals Vascular risk burden is a key player in the early progression of Alzheimer's disease

2021 ◽  
Author(s):  
João Pedro Ferrari-Souza ◽  
Wagner S. Brum ◽  
Lucas A. Hauschild ◽  
Lucas U. Da Ros ◽  
Pâmela C. L. Ferreira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Decline ◽  
Vascular Risk Factor ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Preclinical Alzheimer’S Disease ◽  
Risk Factor Burden

Understanding whether vascular risk factors synergistically potentiate Alzheimer's disease progression is important in the context of emerging treatments for preclinical Alzheimer's disease. The existence of a synergistic relationship could suggest that the combination of therapies targeting Alzheimer's disease pathophysiology and vascular risk factors might potentiate treatment outcomes. In the present retrospective cohort study, we tested whether vascular risk factor burden interacts with Alzheimer's disease pathophysiology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired subjects. We evaluated 503 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Baseline vascular risk factor burden was calculated considering the history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, stroke or transient ischemic attack, smoking, atrial fibrillation, and left ventricular hypertrophy. Alzheimer's disease pathophysiology was evaluated using cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42) reflecting brain amyloidosis (A) and tau phosphorylated at threonine 181 (p-tau181) reflecting brain tau pathology (T). Individuals were dichotomized as having an elevated vascular risk factor burden (V+ if having two or more vascular risk factors) and as presenting preclinical Alzheimer's disease [(AT)+ if having abnormal CSF p-tau181 and Aβ1-42 levels]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. Linear mixed-effects models revealed that an elevated vascular risk factor burden synergistically interacted with Alzheimer's disease pathophysiology to drive longitudinal increases in plasma NfL levels (β = 5.08, P = 0.016) and cognitive decline (β = -0.43, P = 0.020). Additionally, we observed that vascular risk factor burden was not associated with CSF Aβ1-42 or p-tau181 changes over time. Survival analysis demonstrated that individuals with preclinical Alzheimer's disease and elevated vascular risk factor burden [(AT)+V+] had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio = 3.5, P < 0.001). Our results support the notion that vascular risk factor burden and Alzheimer's disease pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive decline. These findings can help in providing the blueprints for the combination of vascular risk factor management and Alzheimer's disease pathophysiology treatment in preclinical stages. Moreover, we observed plasma NfL as a robust marker of disease progression that may be used to track therapeutic response in future trials.

scholarly journals Association of Sleep Disturbances and Cognitive Decline among Cognitively Normal Elders Over Time

2021 ◽  
Author(s):  
Wei Feng ◽  
Mandela William Nzoyoum Kuetche ◽  
Meng Zhang ◽  
MengMeng Liu ◽  
Deginet Aklilu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Regression Models ◽  
Sleep Disturbances ◽  
Amyloid Pet ◽  
Longitudinal Impact ◽  
Cognitively Normal ◽  
Over Time

Abstract Background: While sleep disturbances (SD) has been shown to be associated with worse cognition, but the causal relationship between the two subjects to debate. Our objective was to investigate the longitudinal impact of SD on cognitive function.Objective: To determine the effect of self-reported clinical diagnosis of SD on longitudinal changes in brain amyloid-PET, CSF-biomarkers (Aβ42, T-tau and P-tau) and cognitive function in cognitively normal.Methods: A total of 463 cognitively normal elders (357 normal and 106 SD) were included. Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants were collected from 2005 to 2020. The generalized linear mixed models adjusting variables which were selected by the Akaike Information Criterion (AIC) and the marginal effect estimation method was used to estimate the risk effect of SD. Cox proportional hazards regression models estimated the relative hazard of Alzheimer’s Disease (AD), among baseline SD patients.Results: The age range of participants was 73.60±5.71 years old, and the female proportion was 43.63%. In adjusted regression models, Participants with baseline SD had higher likelihood of developing worse cognition over subsequent follow-up, PACC (decrease 7.53 points [95%CI, 7.36-7.70]; P<0.001), MMSE (decrease 5.26 points [95%CI, 5.17-5.35]; P<0.001), and CDR–Sum of Boxes (increase 5.61 points [95%CI, 5.67-5.54]; P=0.001). Similarly, Cox regression analysis suggested that sleep disturbances is a risk factor of AD (HR=1.55, 95% CI=1.08 to 2.22).Conclusion: SD probably is a warning sign of AD, because it is associated with greater likelihood of cognitive decline or dementia over time. Associations are likely multifactorial and could be explained by intervening variables in the path from SD to dementia, or by common risk factors for pathological processes in brain. These findings suggest need for more attentions of older adults with sleep compromise.

Sign in / Sign up

Export Citation Format

Share Document