scholarly journals Association Between sTREM2, an Immune Biomarker of Microglial Activation, and Aging-Related Brain Volume Changes in Community-Dwelling Older Adults: A 7-Year Follow-Up Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryuzo Orihashi ◽  
Yoshito Mizoguchi ◽  
Yoshiomi Imamura ◽  
Shigeto Yamada ◽  
Akira Monji

BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in older adults.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and clinical dementia rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and higher CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal.ConclusionSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in older adults aged 65 years and above.

2020 ◽  
Author(s):  
Ryuzo Orihashi ◽  
Yoshito Mizoguchi ◽  
Yoshiomi Imamura ◽  
Shigeto Yamada ◽  
Akira Monji

Abstract BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in elderly people.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal. ConclusionsSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in elderly people aged 65 years and above.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Ryuzo Orihashi ◽  
Yoshito Mizoguchi ◽  
Yoshiomi Imamura ◽  
Shigeto Yamada ◽  
Takefumi Ueno ◽  
...  

Abstract Oxytocin is deeply involved in human relations. In recent years, it is becoming clear that oxytocin is also involved in social cognition and social behaviour. Oxytocin receptors are also thought to be present in the hippocampus and amygdala, and the relationship between oxytocin and the structure and function of the hippocampus and amygdala has been reported. However, a few studies have investigated oxytocin and its relationship to hippocampus and amygdala volume in elderly people. The aim of this study is to investigate the association between serum oxytocin levels and hippocampus and amygdala volume in elderly people. The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum oxytocin level measurements, brain MRI, Mini–Mental State Examination and Clinical Dementia Rating were performed in Time 1 (2009–11). Follow-up brain MRI, Mini–Mental State Examination and Clinical Dementia Rating were performed in Time 2 (2016–17). The interval between Time 1 and Time 2 was about 7 years. Fifty-eight participants (14 men, mean age 72.36 ± 3.41 years, oxytocin 0.042 ± 0.052 ng/ml; 44 women, mean age 73.07 ± 4.38 years, oxytocin 0.123 ± 0.130 ng/ml) completed this study. We analysed the correlation between serum oxytocin levels (Time 1) and brain volume (Time 1, Time 2 and Times 1–2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping. Analysis at the cluster level (family-wise error; P &lt; 0.05) showed a positive correlation between serum oxytocin levels (Time 1) and brain volume of the region containing the left hippocampus and amygdala (Time 2). This result suggests that oxytocin in people aged 65 years and older may be associated with aging-related changes in hippocampus and amygdala volume.


2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Juan Luis Sanchez-Sanchez ◽  
Kelly V. Giudici ◽  
Sophie Guyonnet ◽  
Julien Delrieu ◽  
Yan Li ◽  
...  

Abstract Background Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition—Aβ42/40) with overall and domain-specific cognitive evolution among older adults. Methods Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1+)) were used, as well as a dichotomy of Aβ42/40. Outcomes were measured annually over 4 years and included the following: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory). Results Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1+ was associated with worse evolution in the CCS (4-year between-group difference: β = −0.14, 95%CI = −0.26, −0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1+ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ42/40× MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables. Conclusions Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ42/40.


2021 ◽  
Author(s):  
Juan Luis Sanchez-Sanchez ◽  
Kelly V Giudici ◽  
Sophie Guyonnet ◽  
Delrieu Julien ◽  
Li Yan ◽  
...  

Abstract BackgroundMonocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition - Aβ42/40) with overall and domain-specific cognitive evolution among older adults.MethodsSecondary analyses including 1,097 subjects (mean age=75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1+)) were used, as well as a dichotomy of Aβ42/40. Outcomes were measured annually over 4 years and included: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory). ResultsPlasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4-years of follow up, specifically in measures of free and cued delayed recall. MCP-1+ was associated with worse evolution in the CCS (4-year between-group difference: β=-0.14, 95%CI=-0.26, -0.02) and the CDR sum of boxes (2-year: β=0.19, 95%CI=0.06, 0.32). In domain-specific analyses, MCP-1+ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarkers values Aβ42/40 x MCP-1 x time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables.ConclusionsBaseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. Whether plasma MCP-1 interacts with Aβ42/40 to determine cognitive decline should be clarified by further research. The MCP-1 effect on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ42/40.


2021 ◽  
Vol 10 (9) ◽  
pp. 1866
Author(s):  
Javier López ◽  
Maria Inés Serrano ◽  
Isabel Giménez ◽  
Cristina Noriega

A meta-analysis of the efficacy of forgiveness interventions in older adults was conducted. International databases (Medline, PsycINFO, Scopus, Web of Science) were searched for studies published from 1990 to 2020 that attempted to promote forgiveness in older adults. Most intervention studies are group treatments targeted towards community-dwelling older adults. Participants in these studies are mainly women. The intervention objectives and contents vary widely and often criteria are not well-defined. Participants that received forgiveness interventions reported significantly higher levels of forgiveness than participants that did not receive treatment. Additionally, forgiveness interventions resulted in more changes in depression, stress and anger than no intervention conditions. Forgiveness treatment also enhances positive states (satisfaction with life, subjective happiness, and psychological wellbeing). The reported effects are moderate. The specific treatment model (e.g., Enright’s, Worthington’s) and format (e.g., group-based interventions and individually delivered programs) do not differentially predict better outcomes. In conclusion, future intervention studies should include more male participants and utilize a broader range of follow-up periods. Caution must be exercised because of the limited number of studies developed to date; researchers must be cautious when generalizing the results.


Author(s):  
Niklas Sörlén ◽  
Andreas Hult ◽  
Peter Nordström ◽  
Anna Nordström ◽  
Jonas Johansson

Abstract Background We aimed to determine the effectiveness of 4 weeks of balance exercise compared with no intervention on objectively measured postural sway. Methods This was a single-center parallel randomized controlled, open label, trial. A six-sided dice was used for allocation at a 1:1-ratio between exercise and control. The trial was performed at a university hospital clinic in Sweden and recruited community-dwelling older adults with documented postural instability. The intervention consisted of progressively challenging balance exercise three times per week, during 4 weeks, with follow-up at week five. Main outcome measures were objective postural sway length during eyes open and eyes closed conditions. Results Sixty-five participants aged 70 years (balance exercise n = 32; no intervention n = 33) were randomized. 14 participants were excluded from analysis because of early dropout before follow-up at week five, leaving 51 (n = 22; n = 29) participants for analysis. No significant differences were detected between the groups in any of the postural sway outcomes. Within-group analyses showed significant improvements in hand grip strength for the intervention group, while Timed Up & Go improvements were comparable between groups but only statistically significant in the control group. Conclusions Performing balance exercise over a four-week intervention period did not acutely improve postural sway in balance-deficient older adults. The lower limit in duration and frequency to achieve positive effects remains unclear. Trial registration Clinical trials NCT03227666, July 24, 2017, retrospectively registered.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 407
Author(s):  
Laetitia Lengelé ◽  
Olivier Bruyère ◽  
Charlotte Beaudart ◽  
Jean-Yves Reginster ◽  
Médéa Locquet

This study aimed to assess the impact of malnutrition on the 5-year evolution of physical performance, muscle mass and muscle strength in participants from the SarcoPhAge cohort, consisting of community-dwelling older adults. The malnutrition status was assessed at baseline (T0) according to the “Global Leadership Initiatives on Malnutrition” (GLIM) criteria, and the muscle parameters were evaluated both at T0 and after five years of follow-up (T5). Lean mass, muscle strength and physical performance were assessed using dual X-ray absorptiometry, handgrip dynamometry, the short physical performance battery test and the timed up and go test, respectively. Differences in muscle outcomes according to nutritional status were tested using Student’s t-test. The association between malnutrition and the relative 5-year change in the muscle parameters was tested using multiple linear regressions adjusted for several covariates. A total of 411 participants (mean age of 72.3 ± 6.1 years, 56% women) were included. Of them, 96 individuals (23%) were diagnosed with malnutrition at baseline. Their muscle parameters were significantly lower than those of the well-nourished patients both at baseline and after five years of follow-up (all p-values < 0.05), except for muscle strength in women at T5, which was not significantly lower in the presence of malnutrition. However, the 5-year changes in muscle parameters of malnourished individuals were not significantly different than those of well-nourished individuals (all p-values > 0.05).


2021 ◽  
Author(s):  
K Makino ◽  
S Lee ◽  
S Bae ◽  
I Chiba ◽  
K Harada ◽  
...  

Abstract Objective The present study aimed to examine the prospective associations of physical frailty with future falls and fear of falling (FOF) among community-dwelling older adults. Methods A prospective cohort study with a 48-month follow-up was conducted in a Japanese community. Participants were 2469 community-dwelling older adults aged 65 years or older who completed baseline and follow-up assessments at intervals of 48±2 months. Primary outcomes were recent falls (defined as at least one fall within the past year) and FOF (determined by response to “Are you afraid of falling?”) at follow-up survey. Physical frailty, operationalized by the frailty phenotype (slowness, weakness, exhaustion, weight loss, and low activity) based on the criteria of the Japanese version of the Cardiovascular Health Study (J-CHS), was also assessed as a predictor of future falls and FOF. Results Multivariate logistic regression showed that pre-frailty or frailty increase the risk of not only future falls (OR: 1.57; 95%CI = 1.20-2.05) but also FOF (OR: 1.33; 95%CI = 1.05-1.69). In addition, the relationship between baseline frailty status and future falls remained significant after adjusting for baseline FOF (OR: 1.55; 95%CI = 1.19-2.02), and the relationship between baseline frailty status and future FOF also remained significant after adjusting for baseline falls (OR: 1.32; 95%CI = 1.04-1.68). Conclusions Frailty status may predict future falls and FOF among community-dwelling older adults. Strategies to prevent frailty may be beneficial to prevent not only future falls but also future FOF in a community setting. Impact Falls and FOF have a close relationship but a different clinical meaning. Older adults with physical frailty may require monitoring as high-risk not only for falls but also for FOF.


2021 ◽  
pp. 1-17
Author(s):  
Taeko Makino ◽  
Hiroyuki Umegaki ◽  
Masahiko Ando ◽  
Xian Wu Cheng ◽  
Koji Ishida ◽  
...  

Background: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified. Objective: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC). Methods: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions. Results: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82–3.66] points) than the control group (1.36 [0.44–2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups. Conclusion: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline.


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