scholarly journals Interactions Between Plasma Amyloid and Aging Markers to Determine Clinically Meaningful Cognitive Decline

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 699-700
Author(s):  
Wan-Hsuan Lu ◽  
Kelly Giudici ◽  
Bruno Vellas ◽  
Philipe de Souto Barreto
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Mitochondrial Dysfunction ◽  
Cox Regression ◽  
Amyloid Β ◽  
Community Dwelling ◽  
Clinical Dementia Rating ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Monocyte Chemoattractant Protein 1

Abstract Background Brain amyloidosis is a well-known pathological hallmark of Alzheimer’s disease (AD) and can be early identified by measuring plasma amyloid-β (Aβ) status. Growing evidence implicates the biological mechanisms of aging, including chronic inflammation, mitochondrial dysfunction and neurodegeneration, in AD pathogenesis. This study aims to investigate the interactions between plasma Aβ status and aging markers on clinically meaningful cognitive decline. Methods This secondary analysis from Multidomain Alzheimer Preventive Trial (MAPT) enrolled 401 community-dwelling older adults (mean age ± SD: 76.7 ± 4.6 years) who had clinical dementia rating (CDR) scale as 0 or 0.5, and who had their plasma biomarkers measured: amyloidosis: Aβ42/40 ratio; inflammatory: tumor necrosis factor receptor type 1 (TNFR-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP); mitochondrial dysfunction: growth differentiation factor 15 (GDF-15); neurodegeneration: neurofilament light chain (NfL). Cognitive decline was determined by diagnosed dementia and worsening CDR status. Cox regression and moderation modeling were applied to examine the interrelationships between biomarkers and risk of cognitive decline. Results Among 401 participants, 43.9% were cognitive normal (CDR=0) and 56.1% were mild cognitive impairment (CDR=0.5) initially. After 3.3 ± 1.1 years of follow-up, 7.0% of population evolved dementia and 34.2% had worsening CDR status. GDF-15 and NfL presented prospective associations with incident dementia. However, risk of dementia associated with plasma Aβ did not change after considering the serum level of GDF-15 and NfL. Conclusion The markers of mitochondrial dysfunction and neurodegeneration did not partially explain the associations between plasma Aβ status and cognitive decline in older adults.

Interactions between weight loss and plasma neurodegenerative markers for determining cognitive decline among community-dwelling older adults

2022 ◽  
Author(s):  
Kelly Virecoulon Giudici ◽  
Sophie Guyonnet ◽  
John E Morley ◽  
Andrew D Nguyen ◽  
Geetika Aggarwal ◽  
...  
Keyword(s):  
Older Adults ◽  
Weight Loss ◽  
Cognitive Decline ◽  
Community Dwelling ◽  
Composite Score ◽  
Digit Symbol Substitution Test ◽  
Clinical Dementia Rating ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Category Naming

Abstract This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β42/40 (Aβ42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8y (SD=4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onwards by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test, Digit Symbol Substitution Test, ten MMSE orientation items (MMSEO) and Free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL+lower Aβ42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p<0.0001) and MMSEO (p=0.021), compared to non-WL+higher Aβ42/40. WL+higher NfL (>94.55pg/mL, highest quartile) or progranulin (>38.4ng/mL, three higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO and composite score (all p<0.03), compared to non-WL+lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs. Q4) revealed higher cognitive decline among the WL+lower progranulin group compared to non-WL+lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment.

scholarly journals Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Juan Luis Sanchez-Sanchez ◽  
Kelly V. Giudici ◽  
Sophie Guyonnet ◽  
Julien Delrieu ◽  
Yan Li ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
Continuous Variable ◽  
Community Dwelling ◽  
Clinical Dementia Rating ◽  
Delayed Recall ◽  
Domain Specific

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.

scholarly journals Plasma amyloid‐β 42/40 as a predictor of cognitive decline among community‐dwelling older adults: MAPT study

2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Kelly V Giudici ◽  
Philipe de Souto Barreto ◽  
Yan Li ◽  
Randall J Bateman ◽  
Bruno Vellas ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Community Dwelling ◽  
Community Dwelling Older Adults

scholarly journals Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingxiao He ◽  
John E. Morley ◽  
Geetika Aggarwal ◽  
Andrew D. Nguyen ◽  
Bruno Vellas ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Light Chain ◽  
Cognitive Functions ◽  
Linear Models ◽  
Cognitive Status ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
State Examination

AbstractNeurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer’s Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β =  − 0.007, 95% CI [− 0.013, − 0.001]; CCS: β =  − 0.003, 95% CI [− 0.006, − 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β =  − 0.003, 95% CI [− 0.005, − 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β =  − 0.07, 95% CI [− 0.12, − 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.

scholarly journals Plasma MCP-1 and Changes on Cognitive Function in Community-Dwelling Older Adults

2021 ◽  
Author(s):  
Juan Luis Sanchez-Sanchez ◽  
Kelly V Giudici ◽  
Sophie Guyonnet ◽  
Delrieu Julien ◽  
Li Yan ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
Community Dwelling ◽  
Z Score ◽  
Clinical Dementia Rating ◽  
Delayed Recall ◽  
Domain Specific

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.

scholarly journals Temporal trajectory of biofluid markers in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min Seok Baek ◽  
Myung Jun Lee ◽  
Han-Kyeol Kim ◽  
Chul Hyoung Lyoo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Amyloid Β ◽  
Rapid Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Using Data ◽  
Negative Exponential ◽  
T Tau

AbstractFull dynamics of biofluid biomarkers have been unknown in patients with Parkinson’s disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF α-synuclein (α-syn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF α-syn, Aβ, t-tau and p-tau levels than those of the controls. In all PD patients, CSF α-syn and Aβ decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of Aβ and α-syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low Aβ group showed earlier decline of α-syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high Aβ group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and Aβ burden at baseline. PD patients with Aβ pathology may be associated with early appearance of α-synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.

The Brief Odor Detection Test (B-ODT) for Very Early Diagnosis of Cognitive Decline: A Preliminary Study

2017 ◽  
Vol 18 (2) ◽  
pp. 197-210
Author(s):  
Dimitra Savvoulidou ◽  
Efthymia Totikidou ◽  
Chariklia Varvesiotou ◽  
Magda Iakovidou ◽  
Ourania Sfakianaki ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Adult Population ◽  
Detection Threshold ◽  
Community Dwelling ◽  
Odor Detection ◽  
Olfactory Impairment ◽  
Older Adult Population ◽  
Community Dwelling Older Adults

Olfactory impairment in older adults is associated with cognitive decline. This study describes the development of a Brief Odor Detection Test (B-ODT), and its pilot administration in community-dwelling older adults. The study aimed at examining whether the test could differentiate older adults with very mild cognitive impairment from their cognitively healthy counterparts. The sample consisted of 34 older adults (22 women), aged from 65 to 87 years. Participants were divided into two groups according to their general cognitive functioning. Odor detection was measured via vanillin solutions at the following concentrations: 150 mg/L, 30 mg/L, 15 mg/L, 3 mg/L, and .03 mg/L. The first condition of the test involved a scale administration of vanillin solutions. The second condition examined the change in air odour and it required vanillin solution of 30 mg/L and a metric ruler of 30 cm. The examiner had to place the solution at a specific distance point from each nostril. Odour identification sensitivity was secondarily measured. The results showed statistically significant differences in odour detection threshold between the two groups. In the unirhinal testing, left nostril differences of the two groups were definite. Hence, the B-ODT seems a promising instrument for very early cognitive impairment screening in older adult population.

scholarly journals The ACHIEVE Trial: Lessons Learned From Nesting a Randomized Controlled Trial Within an Observational Cohort Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 811-811
Author(s):  
Jennifer Deal ◽  
Nicholas Reed ◽  
David Couper ◽  
Kathleen Hayden ◽  
Thomas Mosley ◽  
...  
Keyword(s):  
Older Adults ◽  
Randomized Controlled Trial ◽  
Observational Study ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Lessons Learned ◽  
Community Dwelling ◽  
Randomized Controlled ◽  
Study Staff ◽  
Increased Risk

Abstract Hearing impairment in older adults is linked to accelerated cognitive decline and a 94% increased risk of incident dementia in population-based observational studies. Whether hearing treatment can delay cognitive decline is unknown but could have substantial clinical and public health impact. The NIH-funded ACHIEVE randomized controlled trial of 977 older adults aged 70-84 years with untreated mild-to-moderate hearing loss, is testing the efficacy of hearing treatment versus health education on cognitive decline over 3 years in community-dwelling older adults (Clinicaltrials.gov Identifier: NCT03243422.) This presentation will describe lessons learned from ACHIEVE’s unique study design. ACHIEVE is nested within a large, well-characterized multicenter observational study, the Atherosclerosis Risk in Communities Study. Such nesting within an observational study maximizes both operational and scientific efficiency. With trial results expected in 2022, this presentation will focus on the benefits gained in design and recruitment/retention, including dedicated study staff, well-established protocols, and established study staff-participant relationships. Part of a symposium sponsored by Sensory Health Interest Group.

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations

2021 ◽  
pp. 1-9
Author(s):  
Gihwan Byeon ◽  
Min Soo Byun ◽  
Dahyun Yi ◽  
Jun Ho Lee ◽  
So Yeon Jeon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Older Adults ◽  
Cognitive Decline ◽  
Brain Atrophy ◽  
Homocysteine Level ◽  
Cognitive Impairments ◽  
Interactive Effect ◽  
Brain Mri ◽  
Amyloid Β ◽  
Serum Homocysteine

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer’s disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

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