Subsequent Cognitive Decline Research Articles

Associations Between Atherosclerosis and Subsequent Cognitive Decline: A Prospective Cohort Study.

This study aimed to examine whether baseline atherosclerosis was associated with subsequent short-term domain-specific cognitive decline. This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population-based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima-media thickness, carotid plaques, coronary artery calcification, and brachial-ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022-2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima-media thickness, carotid plaques, and brachial-ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima-media thickness (β=-0.065 SD/y [95% CI, -0.112 to -0.017]; P=0.008), carotid plaques (β=-0.070 SD/y [95% CI, -0.130 to -0.011]; P=0.021), and brachial-ankle pulse wave velocity (β=-0.057 SD/y [95% CI, -0.105 to -0.010]; P=0.018), and a coronary artery calcification score≥400 (β=-0.081 SD/y [95% CI, -0.153 to -0.008]; P=0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima-media thickness, coronary artery calcification, and brachial-ankle pulse wave velocity were significantly associated with a faster decline in global cognition. More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

Latent change-on-change between amyloid accumulation and cognitive decline.

While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored. A series of bivariate latent change score models (LCSM) examined the relationship between changes in 11C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS). Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope. Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau. Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse theeffects of MTL tau.

HIV Stigma is Associated with Two-Year Decline in Cognitive Performance Among People with HIV.

HIV stigma is associated with suboptimal clinical outcomes and has been cross-sectionally linked to cognitive deficits in people with HIV (PWH). However, it is unclear whether HIV stigma precedes cognitive decline or vice versa. We examined associations in 303 adult PWH (mean age 50.01 (11.91) years; 46% female; 67% non-Hispanic Black) between the abbreviated Berger Stigma Scale score and longitudinal change across the NIH Toolbox Cognition Battery measures. 89% of participants reported experiencing HIV stigma. In unadjusted analyses, greater HIV stigma was associated with worse attention performance at yearly follow-up visits (B = -0.07, 95% CI = -0.13 - -0.01, p = 0.025). When adjusting for clinicodemographic variables, HIV stigma was associated with worse processing speed and global cognition at yearly follow-up visits. This finding suggests that HIV stigma precedes subsequent cognitive decline and highlights the importance of reducing stigma to improve cognitive functioning among PWH.

A Lack of Food for Thought: Midlife Food Insecurity and Its Association With Subsequent Cognitive Ability of Older Americans.

The 50-59 age group in the United States experience higher levels of food insecurity (FI) compared to older adults. While previous research has identified an association between FI and cognition outcomes in older populations, limited research has examined midlife as a specific FI exposure window and the association of this hardship with long-run cognition outcomes. Utilizing 14 waves of Health and Retirement Study (HRS) data (1995-2020), I applied mixed-effects models to assess the relationship between midlife FI exposure and later-life cognitive function, controlling for childhood disadvantages and other health-related and sociodemographic characteristics. Findings indicate that both cumulative FI duration and ever experiencing FI during ages 50-59 are significantly associated with subsequent cognitive decline. Specifically, ever experiencing FI during midlife was linked to a decrease in cognitive function by 0.07 standard units (95% confidence interval [CI], -0.13 to -0.003; p < .05). In addition, each additional year of FI exposure during midlife was associated with a reduction in cognitive function by 0.01 standard units (95% CI: -0.03 to -0.003; p < .05). These associations remained robust even after accounting for a range of potential confounders and covariates. The findings support the cumulative inequality model, suggesting that midlife FI is a significant predictor of lower cognitive function in later life. Both the timing and extent of FI during midlife are crucial factors in shaping cognitive health outcomes. Policy interventions targeting FI in the 50-59 age group could play a pivotal role in promoting healthy aging and mitigating cognitive decline in older adulthood.

Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults.

Animal and computational models of Alzheimer's disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial-temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phases of AD.

α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.

Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn "strains" - conformations with distinct biological properties. However, biomarkers for PD vs. DLB, including potential aSyn strain differences, are lacking. Here, we used two monoclonal antibodies selective for different in vitro aSyn species - termed Strain A and B - to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. Surprisingly, levels of Strain A and B aSyn species differed in plasma from individuals with PD vs. DLB in two independent cohorts. Lower plasma aSyn Strain A species also predicted subsequent PD cognitive decline. Strain A and Strain B aSyn species were undetectable in CSF, but plasma aSyn species could template aSyn fibrillization, particularly in PD. Our findings suggest that aSyn strains may impact LBD clinical presentation and originate outside the brain.

Herpes zoster and long-term risk of subjective cognitive decline

BackgroundHerpes zoster (HZ), commonly known as “shingles,” may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking.MethodsWe included 149,327 participants from three large cohorts—the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)—to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD). Poisson regression was used to estimate the multivariable-adjusted relative risk (MVRR) of a 3-unit increment in SCD score according to years since HZ compared with participants with no history of HZ.ResultsCompared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was significantly and independently higher among individuals with a history of HZ, but the duration of time since HZ when the elevated risk of SCD was statistically significant differed among the cohorts. In NHS, HZ was associated with higher long-term risk of SCD; compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was 1.14 (1.01, 1.32) for ≥ 13 years since HZ. In NHS II, HZ was associated with higher risk of SCD in both the short-term [MVRR 1.34 (1.18, 1.53) for 1–4 years] and long-term [MVRR 1.20 (1.08, 1.34) for ≥ 13 years since HZ]. In HPFS, an elevated risk of SCD was suggested across all time points. Among the subset of participants with information on APOE ε4, there was a suggestion that the association differed by APOE ε4 carrier status, but the results were not consistent between women and men. Among the subset of women with information on HZ vaccination, there was a suggestion that the long-term risk of SCD may be greater among women who were not vaccinated against HZ.ConclusionsData from three large independent cohorts of women and men showed that HZ was associated with higher long-term risk of SCD, and the risk may differ by APOE ε4-carrier status.

Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.

Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

Trajectories of pain and their associations with long-term cognitive decline in older adults: evidence from two longitudinal cohorts.

Pain is a dynamic experience that varies over time, but it remains unknown whether trajectories of pain are associated with subsequent cognitive decline. The purpose of this study was to identify distinct trajectories of pain presence and activity-limiting pain and investigate their longitudinal associations with the rate of subsequent cognitive decline in older adults. A total of 5685 participants from the English Longitudinal Study of Ageing (ELSA) and 7619 participants from the Health and Retirement Study (HRS) were included. Pain presence trajectories were identified over eightyears in the ELSA and 10years in the HRS, while trajectories of activity-limiting pain were identified over 10years in the HRS. We utilised linear mixed-effects models to investigate the long-term relationship between pain trajectories and the rate of cognitive decline across various domains, including memory, orientation, executive function and global cognition. Three pain presence trajectories were identified. Moderate-increasing and high-stable groups exhibited steeper declines in global cognition than the low-stable group. Furthermore, individuals in the moderate-increasing group experienced a more rapid decline in executive function, while the high-stable group showed a faster decline in orientation function. Two trajectories of activity-limiting pain were identified, with the moderate-increasing group experiencing a faster decline in orientation function and global cognition. The trajectories of both pain presence and activity-limiting pain are linked to the rate of subsequent cognitive decline among older people. Interventions for specific pain trajectories might help to delay the decline rate of cognition in specific domains.

Role of Cardiac Biomarkers in Stroke and Cognitive Impairment.

This topical review assesses the growing role of cardiac biomarkers beyond cardiovascular health and focuses on their importance in stroke and dementia. The first part describes blood-based cardiac biomarkers in patients with stroke and highlights applications in the setting of early diagnosis, poststroke complications, outcome prediction as well as secondary prevention. Among other applications, natriuretic peptides can be helpful in differentiating stroke subtypes. They are also currently being investigated to guide prolonged ECG monitoring and secondary prevention in patients with stroke. Elevated cardiac troponin after ischemic stroke can provide information about various poststroke complications recently termed the stroke-heart syndrome. The second part focuses on the role of cardiac biomarkers in vascular cognitive impairment and dementia, emphasizing their association with structural brain lesions. These lesions such as silent brain infarcts and white matter hyperintensities often co-occur with cardiac disease and may be important mediators between cardiovascular disease and subsequent cognitive decline. ECG and echocardiogram measurements, in addition to blood-based biomarkers, show consistent associations with vascular brain changes and incident dementia, suggesting a role in indicating risk for cognitive decline. Together, the current evidence suggests that cardiac blood-based, electrophysiological, and imaging biomarkers can be used to better understand the heart and brain connection in the setting of not only stroke but also dementia.

Exercise to Counteract Alzheimer's Disease: What Do Fluid Biomarkers Say?

Neurodegenerative diseases (NDs) represent an unsolved problem to date with an ever-increasing population incidence. Particularly, Alzheimer's disease (AD) is the most widespread ND characterized by an accumulation of amyloid aggregates of beta-amyloid (Aβ) and Tau proteins that lead to neuronal death and subsequent cognitive decline. Although neuroimaging techniques are needed to diagnose AD, the investigation of biomarkers within body fluids could provide important information on neurodegeneration. Indeed, as there is no definitive solution for AD, the monitoring of these biomarkers is of strategic importance as they are useful for both diagnosing AD and assessing the progression of the neurodegenerative state. In this context, exercise is known to be an effective non-pharmacological management strategy for AD that can counteract cognitive decline and neurodegeneration. However, investigation of the concentration of fluid biomarkers in AD patients undergoing exercise protocols has led to unclear and often conflicting results, suggesting the need to clarify the role of exercise in modulating fluid biomarkers in AD. Therefore, this critical literature review aims to gather evidence on the main fluid biomarkers of AD and the modulatory effects of exercise to clarify the efficacy and usefulness of this non-pharmacological strategy in counteracting neurodegeneration in AD.

Augmentation of perivascular space visualization in basal ganglia and white matter hyperintensity lesion is a meaningful finding for subsequent cognitive decline.

Cerebral small vessel disease (CSVD) causes cognitive decline and perivascular space enlargement is one of the image markers for CSVD. To search for clinical significance in the time-course augmentation of perivascular space in basal ganglia (BG-PVS) for cognitive decline. This study population included 179 participants from a community-based cohort, aged 70 years at baseline. They had undergone magnetic resonance imaging (MRI) studies two or three times between 2000 and 2008. Based on the severity of BG-PVS or white matter hyperintensity lesions (WMHL) in 2000, the participants were divided into low-grade or high-grade groups, respectively. In addition, their time-course augmentation was evaluated, and we created a categorical BG-PVS WMHL change score based on their augmentation (1 = neither, 2 = BG-PVS augmentation only, 3 = WMHL augmentation only, 4 = both). Cognitive function was assessed based on the Mini-Mental State Examination (MMSE); the change was defined as the difference between scores in 2000 and 2008. We used simple or multiple regression analysis for MMSE score change according to MRI findings and clinical characteristics that were probably related to cognitive decline. In univariate analysis, MMSE score change was negatively associated with BG-PVS high grade at baseline and BG-PVS WMHL change score 4; this remained significant in multivariate analysis. In the final model based on the Akaike Information Criterion, BG-PVS WMHL change score 4 was associated with a 3.3-point decline in subsequent MMSE score. This study suggested that augmentation in both BG-PVS and WMHL was associated with subsequent cognitive decline.

The Grip Strength Loss Rate and the Subsequent Cognitive Decline Rate in Older Adults: The Moderating Role of Social Isolation.

Accumulating evidence suggests that low grip strength (GS) is associated with a faster cognitive decline, but most previous studies have measured GS at a single time point, ignoring changes in GS. We aimed to explore the association of the GS loss rate with the sequent cognitive decline, as well as the moderating role of social isolation in older adults. Data were from the English Longitudinal Study of Ageing. Absolute and relative GS loss rates were calculated as the annual losses from Wave 2 (2004-05) to Wave 4 (2008-09). Participants were divided into 3 groups according to the tertiles of GS loss rates. Linear mixed models were used to assess the association of the GS loss rate during Waves 2-4 with the cognitive decline rate during Waves 4-9 (Wave 9,2018-19). Of the 4356 participants included in analyses, 1938 (44.5%) were men, with a mean age of 68.4 (SD: 8.4) years. Compared with Tertile 1 of the absolute GS loss rate, Tertile 2 (β = -0.009 [95% CI: -0.018 to -0.001] SD/year) and Tertile 3 (β = -0.018 [95% CI: -0.027 to -0.010] SD/year) were associated with a faster cognitive decline rate. The results of relative GS were similar to those of absolute GS. Social isolation was a significant modifier in the associations of the absolute GS loss rate with decline rates in global cognition and episodic memory, but not in temporal orientation. We did not observe that social isolation moderated the association of the relative GS loss rate with the cognitive decline rate. Both absolute and relative GS loss rates were positively associated with the cognitive decline rate in older adults. Low social isolation scores attenuated the association of the absolute GS loss rate with the cognitive decline rate.

Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline.

Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention. We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS]). The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score=1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and=1.15 [1.08; 1.22] in carriers; P=0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline. Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia.

Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging.

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence-associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Association between untreated and treated blood pressure levels and cognitive decline in community-dwelling middle-aged and older adults in China: a longitudinal study

BackgroundOptimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults.MethodsThis study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline.ResultsWe included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (β=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (β=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (β=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline.ConclusionsCumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.

Adverse childhood experiences, perceived stress, and chronic diseases among older adults: A cross-sectional study in Mexico

BackgroundAdverse childhood experiences (ACEs) are traumatic events that cause a condition of chronic stress in the body and that are related to subsequent cognitive decline and the development of psychiatric disorders and chronic diseases. ObjectiveThe objective of the present study was to examine the relationship between ACEs, stress, and chronic diseases in older adults. MethodsThis work was a cross-sectional study. We analyzed 450 participants aged 65 and older. To measure ACE, we used the ACE questionnaire that is a 10-item scale to measure the occurrence of a set of experiences during childhood and adolescence. In addition, the perceived stress scale was used as screening tool for stress. Logistic regression models were used to examine the associations between overall ACE score and individual ACE component scores and risk stress/comorbidities in adulthood after controlling for potential confounders. ResultsThe overall prevalence of perceived stress among older adults was 79.1%. Almost 76% of the sample reported being diagnosed with four or more chronic diseases. We found that the risk of stress increased in case of exposure to one-three ACEs (OR = 1.42, CI = [1.19–1.93]) and in case of experiencing at least four or more ACEs (OR = 1.43, CI = [1.23–1.82]). There was a statistical non-significant association between ACE exposure and the presence of chronic diseases. ConclusionTogether our findings demonstrate clear links between ACEs and negative mental health outcomes. Future work will assess these issues in longitudinal studies to examine the long-term impact of ACEs on health outcomes. Physicians should be able to provide clinical interventions for trauma-focused care.

Atrophy links lower novelty-related locus coeruleus connectivity to cognitive decline in preclinical AD.

Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC-MTL functional connectivity (FCLC-MTL) on cortical atrophy across Braak stage regions and its impact on cognition. We analyzed functional magnetic resonance imaging and amyloid beta (Aβ) positron emission tomography data from 128 cognitively normal participants, associating novelty-related FCLC-MTL with longitudinal atrophy and cognition with and without Aβ moderation. Cross-sectionally, lower FCLC-MTL was associated with atrophy in Braak stage II regions. Longitudinally, atrophy in Braak stage 2 to 4 regions related to lower baseline FCLC-MTL at elevated levels of Aβ, but not to other regions. Atrophy in Braak stage 2regions mediated the relation between FCLC-MTL and subsequent cognitive decline. FCLC-MTL is implicated in Aβ-related cortical atrophy, suggesting that LC-MTL connectivity could confer neuroprotective effects in preclinical AD. Novelty-related functional magnetic resonance imaging (fMRI) LC-medial temporal lobe (MTL) connectivity links to longitudinal Aβ-dependent atrophy. This relationship extended to higher Braak stage regions with increasing Aβ burden. Longitudinal MTL atrophy mediated the LC-MTL connectivity-cognition relationship. Our findings mirror the animal data on MTL atrophy following NE signal dysfunction.

Neuronal microstructural changes in the human brain are associated with neurocognitive aging.

Gray matter (GM) alterations play a role in aging-related disorders like Alzheimer's disease and related dementias, yet MRI studies mainly focus on macroscopic changes. Although reliable indicators of atrophy, morphological metrics like cortical thickness lack the sensitivity to detect early changes preceding visible atrophy. Our study aimed at exploring the potential of diffusion MRI in unveiling sensitive markers of cortical and subcortical age-related microstructural changes and assessing their associations with cognitive and behavioral deficits. We leveraged the Human Connectome Project-Aging cohort that included 707 participants (394 female; median age = 58, range = 36-90 years) and applied the powerful mean apparent diffusion propagator model to measure microstructural parameters, along with comprehensive behavioral and cognitive test scores. Both macro- and microstructural GM characteristics were strongly associated with age, with widespread significant microstructural correlations reflective of cellular morphological changes, reduced cellular density, increased extracellular volume, and increased membrane permeability. Importantly, when correlating MRI and cognitive test scores, our findings revealed no link between macrostructural volumetric changes and neurobehavioral performance. However, we found that cellular and extracellular alterations in cortical and subcortical GM regions were associated with neurobehavioral performance. Based on these findings, it is hypothesized that increased microstructural heterogeneity and decreased neurite orientation dispersion precede macrostructural changes, and that they play an important role in subsequent cognitive decline. These alterations are suggested to be early markers of neurocognitive performance that may distinctly aid in identifying the mechanisms underlying phenotypic aging and subsequent age-related functional decline.