Shared biological pathways for frailty and cognitive impairment: A systematic review.
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ABSTRACT:
SUBMITTER: Sargent L
PROVIDER: S-EPMC6376483 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Shared biological pathways for frailty and cognitive impairment: A systematic review.
Sargent Lana L Nalls Mike M Starkweather Angela A Hobgood Sarah S Thompson Holly H Amella Elaine J EJ Singleton Andrew A
Ageing research reviews 20180810
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Project description:IntroductionWe describe findings from a large study that provide empirical support for the emerging construct of cognitive frailty and put forth a theoretical framework that may advance the future study of complex aging conditions. While cognitive impairment and physical frailty have long been studied as separate constructs, recent studies suggest they share common etiologies. We aimed to create a population predictive model to gain an understanding of the underlying biological mechanisms for the relationship between physical frailty and cognitive impairment.MethodsData were obtained from the longitudinal "Invecchaiare in Chianti" (Aging in Chianti, InCHIANTI Study) with a representative sample (n = 1453) of older adults from two small towns in Tuscany, Italy. Our previous work informed the candidate 132 single nucleotide polymorphisms (SNPs) and 155 protein biomarkers we tested in association with clinical outcomes using a tree boosting, machine learning (ML) technique for supervised learning analysis.ResultsWe developed two highly accurate predictive models, with a Model I area under the curve (AUC) of 0.88 (95% confidence interval [CI] 0.83-0.90) and a Model II AUC of 0.86 (95% CI 0.80-0.90). These models indicate cognitive frailty is driven by dysregulation across multiple cellular processes including genetic alterations, nutrient and lipid metabolism, and elevated levels of circulating pro-inflammatory proteins.DiscussionWhile our results establish a foundation for understanding the underlying biological mechanisms for the relationship between cognitive decline and physical frailty, further examination of the molecular pathways associated with our predictive biomarkers is warranted. Our framework is in alignment with other proposed biological underpinnings of Alzheimer's disease such as genetic alterations, immune system dysfunction, and neuroinflammation.
| S-EPMC7362211 | biostudies-literature
Project description:Although immediate early genes (IEGs) such as Bdnf, Arc and Egr1, have been implicated in plasticity, the larger pathways related to memory and memory disorders are not well understood. Here, we combined statistical Affymetrix microarray and behavioral analyses to identify key genes and pathways associated with aging-related cognitive impairment. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal). ANOVA, linear contrasts, and overrepresentation analyses identified genes and pathways that differed from Y generally with aging (in both AU and AI) or selectively with cognitive status (only in AI or AU). Plasticity pathways, including insulin/cAMP/IEG signaling, and glycogenolytic and lipogenic pathways, were selectively downregulated (5 days) in AI, whereas Notch2 (regulating oligodendrocyte differentiation) and myelination pathways were upregulated (particularly at 21 days). Downregulation with general aging occurred in signal transduction and axonal growth/transport pathways, whereas upegulation occurred in immune/inflammatory, lipid metabolism/transport (e.g., Lxr-Srebf1), and lysosomal pathways. In AU, receptor/signal transduction genes were selectively upregulated, suggesting possible compensatory mechanisms. Immunohistochemistry confirmed and extended results to the protein level. Thus, this study identified novel cognition-linked processes, suggesting a new model in which energy-intensive, plasticity/lipogenic processes and energy-generating pathways necessary for learning are coordinately downregulated during training, while myelinogenic programs that impair cognition are concurrently activated. Keywords: Immediate Early Genes, Insulin Signaling, Cholesterol, Myelination, Glia, Inflammation, Young and Old comparaison, behavioral-characterization, Aging-related cognitive impairment.
2007-03-15 | GSE5666 | GEO
Project description:AimsThis study analyzes the impact of frailty, mild cognitive impairment, and cognitive frailty on adverse outcomes in community-dwelling older adults.MethodsThis systematic review and meta-analysis were conducted using the PRISMA guidelines and MOOSE statement. We developed a specific search strategy for each electronic database and searched PubMed, Web of Science, MEDLINE, and Embase from initial records to July 2021. The studies on adverse outcomes of frailty, pre-frailty, mild cognitive impairment, and mild cognitive impairment with pre-frailty and cognitive frailty were included. Two researchers independently extracted data based on a spreadsheet and assessed the risk of bias. The primary outcomes were mortality, dementia, disability, and hospitalization. The second outcome included quality of life and falls. All analysis was conducted by using Review Manager (RevMan) 5.3 software.ResultsA total of 22 cohort studies (71,544 older adults with mean age ranging from 65.1 to 93.6 years) were included with a low risk of bias and high methodological quality with a NOS score ≥7. Compared to robust elders, individuals identified as frailty were associated with a higher risk of mortality (RR = 2.11, 95% CI: 1.57-2.83) and disability (RR = 5.91, 95% CI: 2.37-14.74). Mild cognitive impairment with pre-frailty was associated with mortality (RR = 1.74, 95% CI: 1.48-2.05) and dementia (RR = 4.15, 95% CI: 1.87-9.20). Pre-frailty was associated with a higher risk of mortality (RR = 1.29, 95% CI: 1.11-1.50). Cognitive frailty was associated with higher risk of incident mortality (RR = 2.41, 95% CI: 1.97-2.94), dementia (RR = 3.67, 95% CI: 2.81-4.78), disability (RR = 11.32, 95% CI: 4.14-30.97), and hospitalization (RR = 2.30, 95% CI: 1.60-3.32), as well as poor quality of life.ConclusionCognitive frailty could be a comprehensive psychosomatic predictor for adverse outcomes among older people. Interactions between frailty, mild cognitive impairment, and cognitive frailty on adverse outcomes must be further explored.Systematic review registration[https://inplasy.com/inplasy-2022-5-0064/], identifier [INPLASY202250064].
| S-EPMC9659908 | biostudies-literature
Project description:Background and objectivesOlder patients reaching ESRD have a higher risk of adverse health outcomes. We aimed to determine the association of functional and cognitive impairment and frailty with adverse health outcomes in patients reaching ESRD. Understanding these associations could ultimately lead to prediction models to guide tailored treatment decisions or preventive interventions.Design, setting, participants, & measurementsWe searched MEDLINE, Embase, Web of Science, CENTRAL, CINAHL, PsycINFO, and COCHRANE for original studies published until February 8, 2016 reporting on the association of functional or cognitive impairment or frailty with adverse health outcome after follow-up in patients reaching ESRD either with or without RRT.ResultsOf 7451 identified citations, we included 30 articles that reported on 35 associations. Mean age was >60 years old in 73% of the studies, and geriatric conditions were highly prevalent. Twenty-four studies (80%) reported on functional impairment, seven (23%) reported on cognitive impairment, and four (13%) reported on frailty. Mortality was the main outcome measure in 29 studies (97%), and one study assessed functional status trajectory. In 34 of 35 (97%) associations reported, functional or cognitive impairment or frailty was significantly and independently associated with adverse health outcomes. The majority of studies (83%) were conducted in selected patient populations, mainly patients on incident dialysis.ConclusionsFunctional and cognitive impairment and frailty in patients reaching ESRD are highly prevalent and strongly and independently associated with adverse health outcomes, and they may, therefore, be useful for risk stratification. More research into their prognostic value is needed.
| S-EPMC5012494 | biostudies-literature
Project description:ObjectiveWe performed a systematic review and meta-analysis to study the relationship between cognitive functioning and phenotypic frailty status.MethodsWe searched Pubmed, Cochrane Library and Epistemonikos from 2000 until March 2022, and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Samples included both sexes, age ≥55 years, assessed with standardized measures of the different cognitive domains and the frailty phenotype model and analyzing the relationship between the frailty subtypes pre-frail, frail and robust and specific cognitive function.ResultsEleven studies published from 2008 until March 2022 fulfilled the inclusion criteria, and 10 were included in our meta-analyses. Sample sizes varied from 104 to 4649 individuals. Mean Mini-Mental State Examination (MMSE) scores ranged from 17.0 to 27.6, with mean difference (MD) of -2.55 (95% confidence interval [CI] -3.32, -1.78) in frail compared to robust, MD -1.64 (95% CI -2.21, -1.06) in frail compared to prefrail and MD -0.68 (95% CI -0.94, -0.43) in prefrail compared to robust. In subgroup analyses, frail persons had lower scores in the memory domain with standardized mean difference (SMD) -1.01 (95% CI -1.42, -0.59).ConclusionMMSE scores were significantly lower in frail compared to robust and prefrail persons and in prefrail compared to robust persons. Subgroup analysis of memory revealed significantly poorer scores in frail compared to robust. The results indicate a strong relationship between physical frailty and cognitive impairment suggesting incorporation of cognitive function in frailty assessments.
| S-EPMC9828066 | biostudies-literature
Project description:Dementia has become a major issue that requires urgent measures. The prevention of dementia may be influenced by dietary factors. We focused on green tea and performed a systematic review of observational studies that examined the association between green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. We searched for articles registered up to 23 August 2018, in the PubMed database and then for references of original articles or reviews that examined tea and cognition. Subsequently, the extracted articles were examined regarding whether they included original data assessing an association of green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Finally, we included three cohort studies and five cross-sectional studies. One cohort study and three cross-sectional studies supported the positive effects of green tea intake. One cohort study and one cross-sectional study reported partial positive effects. The remaining one cohort study and one cross-sectional study showed no significant association of green tea intake. These results seem to support the hypothesis that green tea intake might reduce the risk for dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Further results from well-designed and well-conducted cohort studies are required to derive robust evidence.
| S-EPMC6567241 | biostudies-other
Project description:BackgroundLoneliness precedes the onset of cognitive impairment (CI) in older adults. Although the mechanisms through which loneliness "gets under the skin" to influence the risk of developing CI have been conceptually proposed, they are rarely empirically examined. The Evolutionary Theory of Loneliness posits that loneliness as a stressor could cause dysregulations in multiple physiological systems. The current study investigated whether inflammatory, cardiovascular, and kidney biomarkers mediate the longitudinal association between loneliness and CI.MethodsCross-lagged panel models were used to examine the hypothesized relationships, using 2006, 2010, and 2014 waves of data from the Health and Retirement Study (N = 7,037). Loneliness was measured with the 3-item UCLA loneliness scale. CI was assessed with the modified telephone interview for cognitive status. Biomarkers included HbA1C, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, and Cystatin C. Using a stepwise model-building approach, first, the model included only loneliness, CI, and biomarker variables; then, sociodemographic covariates were added; lastly, health status were controlled for.ResultsIn unadjusted and partially adjusted models, loneliness was associated with higher odds of worse cognitive status in an 8-year follow-up. Only HbA1C mediated the longitudinal association between loneliness and CI. However, after further controlling for health status, all associations became nonsignificant.ConclusionsExamining a large number of participants and linking a limited number of biological markers with cognition and loneliness longitudinally, our empirical data did not support theoretical propositions, highlighting the critical importance of controlling for confounders in future studies examining longitudinal mediational relationships underlying loneliness and CI.
| S-EPMC11015400 | biostudies-literature
Project description:BackgroundMore people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia, but we do not know how to reduce deterioration.AimsTo systematically review randomised controlled trials (RCTs) evaluating the effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality or incident dementia.MethodWe reviewed 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes and prioritised primary outcome findings in placebo-controlled studies.ResultsThe strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning.ConclusionsThere was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good-quality RCTs are needed and preliminary evidence suggests these should include trials of psychological group interventions and piribedil.
| S-EPMC3943830 | biostudies-literature
Project description:IntroductionCOVID-19 has a wide range of clinical manifestations. Neurological manifestations in COVID-19 patients were demonstrated during the pandemic, including cognitive impairment. This study aimed to determine any relationship between COVID-19 and cognitive complaints, such as dementia, mild cognitive impairment (MCI), or subjective cognitive decline (SCD).MethodsWe performed a systematic review of MEDLINE via Ebsco, Cochrane EMBASE, SCOPUS, and LILACS electronic databases of observational studies with COVID-19 patients confirmed by serology or PCR who developed new cognitive impairment or deteriorated from previous cognitive impairment after infection. This review protocol was recorded on PROSPERO with registration number CRD 42021241590.ResultsA total of 3.520 articles were retrieved and read. Twenty-two studies were selected for our review. A wide range of cognitive assessment tools (n = 25) was used. The most described affected domains in these studies were executive functions, attention, and episodic memory. Thirteen studies showed a pattern of cognitive impairment in processing speed, inattention, or executive dysfunction assessed through working memory.ConclusionThis review highlights the high frequency of cognitive impairment after COVID-19 infection. However, we were unable to differentiate whether the cognitive impairment found corresponded to mild cognitive impairment or dementia through data from selected studies, and this issue serves as one objective of future studies to be addressed on this topic.
| S-EPMC9014565 | biostudies-literature
Project description:The objective of this study was to examine relationships between dimensions of physical frailty and severity of cognitive impairment in older adults with amnestic mild cognitive impairment (aMCI).The prevalence of physical frailty dimensions including slow gait speed, low physical activity, and low grip strength was examined among 201 sedentary older adults with aMCI. Associations between dimensions of physical frailty and severity of cognitive impairment, as measured with the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and individual dimensions of cognitive function were examined using multiple linear regression models.Greater than 50% of participants met physical frailty criteria on dimensions of slow gait speed, low physical activity and low grip strength. Slower gait speed was associated with elevated severity of cognitive impairment. Both gait speed and physical activity were associated with individual dimensions cognitive function.Dimensions of physical frailty, particularly gait speed, were associated with severity of cognitive impairment, after adjusting for age, sex and age-related factors. Further studies are needed to investigate mechanisms and early intervention strategies that assist older adults with aMCI to maintain function and independence.
| S-EPMC5562508 | biostudies-other