scholarly journals Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults

2020 ◽  
Vol 47 (9) ◽  
pp. 2155-2164 ◽  
Author(s):  
Joana B. Pereira ◽  
Theresa M. Harrison ◽  
Renaud La Joie ◽  
Suzanne L. Baker ◽  
William J. Jagust
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Spatial Patterns ◽  
Clinical Symptoms ◽  
Amyloid Β ◽  
Cognitive Testing ◽  
Cross Sectional ◽  
Pittsburgh Compound B ◽  
Asymptomatic Individuals

Abstract Purpose The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. Methods We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread. Results We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas. Conclusions These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.

scholarly journals Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer’s disease and cognitively unimpaired individuals

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Kok Pin Ng ◽  
Hui Chiew ◽  
Pedro Rosa-Neto ◽  
Nagaendran Kandiah ◽  
Zahinoor Ismail ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Longitudinal Studies ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Cross Sectional Studies

AbstractThe development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-β (Aβ), tau and neurodegeneration in preclinical AD and cognitively-unimpaired individuals in 19 eligible English-language publications (8 cross-sectional studies, 10 longitudinal, 1 both cross-sectional and longitudinal). The cross-sectional studies have consistently shown that NPS, particularly depressive and anxiety symptoms, are associated with higher Aβ. The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time. However, most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology. For the association of NPS and neurodegeneration, two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD, respectively. However, evidence for the association between atrophy and NPS in preclinical AD is less consistent. Therefore, future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N) biomarkers, NPS and cognitive decline, but also to elucidate the contribution of comorbid pathology to preclinical AD.

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.

Partner bereavement and brain pathologies: a propensity score matching study

2021 ◽  
Author(s):  
Jee Wook Kim ◽  
Min Soo Byun ◽  
Jun Ho Lee ◽  
Dahyun Yi ◽  
Min Jung Kim ◽  
...  
Keyword(s):  
Propensity Score ◽  
Cognitive Decline ◽  
Propensity Score Matching ◽  
Cerebral White Matter ◽  
Older Individuals ◽  
Pittsburgh Compound B ◽  
Cerebrovascular Injury ◽  
Positron Emission ◽  
Lifetime Partner

Abstract Background: Partner bereavement is one of life’s greatest stresses and has been suggested to trigger or accelerate cognitive decline and dementia. However, little information is available about potential brain pathologies underlying the association between partner bereavement and cognitive decline. Aims: We aimed to test the hypothesis that lifetime partner bereavement is associated with in vivo human brain pathologies underlying cognitive decline. Method: A total of 319 ever-married older adults between 61 and 90 years of age underwent comprehensive clinical assessments and multimodal brain imaging including [11C] Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, [18F] fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Results: Participants were classified as experiencing no partner bereavement or partner bereavement, and comparisons using propensity score matching (59 cases and 59 controls) were performed. Partner bereavement was significantly associated with higher cerebral white matter hyperintensities (WMH) volume compared to no partner bereavement. Interactions and subsequent subgroup analyses showed that partner bereavement was significantly associated with higher WMH in the older (>75 years) subgroup and among those with no- or low-skill occupations. In addition, partner bereavement at 60 years or over affect WMH volume compared to no partner bereavement, whereas partner bereavement at 60 years did not. No group differences were observed in other brain pathologies between partner bereavement categories. Conclusions: The findings suggest that the partner bereavement may contribute to dementia or cognitive decline by increasing cerebrovascular injury, particularly in older individuals and those with no- or low-skill occupations.

Effect of the Fungus Isaria japonica from the Silkworm on Cognitive Function in Older Adults with Mild Cognitive Decline: A Pilot Study

2021 ◽  
Vol 19 (4) ◽  
pp. 383-387
Author(s):  
Daisuke Furushima ◽  
Yuri Takashima ◽  
Toshiji Miyagawa ◽  
Hiroshi Fujita ◽  
Yuzuki Nomura ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Blood Test ◽  
Mmse Score ◽  
Protective Role ◽  
In Vivo Studies ◽  
Serious Adverse Events ◽  
Silkworm Pupae

Several in vivo studies report that the fungus Isaria japonica grown on silkworm pupae, classified as a Cordycipitaceae, plays a role in preventing memory deficits and may have a protective role against cognitive impairment. The present study investigated the cognitive effects and safety of I. japonica in older adults with mild cognitive decline. Intervention trial was conducted in subjects over 60 years of age with mild cognitive decline (Mini-Mental State Examination [MMSE] score: 20-27). The subjects consumed the I. japonica supplements twice per day for 12 weeks. The outcome measures included the MMSE score and blood test values before and after the intervention. A total of 25 subjects (aged 64-94 years) were eligible for the study. After the intervention, the MMSE score (mean ± standard deviation) significantly increased from 25.5 ± 1.6 to 27.1 ± 2.4 (P < 0.0001). The blood test revealed no change in any of the hematological and biochemical parameters evaluated. Also, no serious adverse events were reported. Despite several limitations in the study design, the findings of the present study suggest that the fungus I. japonica is safe to consume and it may improve cognitive function in older adults with mild cognitive decline.

Abstract 22: Visit-to-Visit Variability in Blood Pressure is Related to Late-Life Cognitive Decline

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Bo Qin ◽  
Anthony J Viera ◽  
Linda S Adair ◽  
Brenda L Plassman ◽  
Lloyd J Edwards ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Verbal Memory ◽  
Repeated Measures ◽  
Community Dwelling ◽  
Cognitive Testing ◽  
Cognitive Test ◽  
Nutrition Survey

Introduction: Recent studies suggest higher visit-to-visit variability of blood pressure (BP) is associated with worse cognitive function, but evidence based on longitudinal cognitive testing has not been reported. Hypothesis: We assessed the hypothesis that higher visit-to-visit variability in BP, but not mean BP, would be associated with faster decline in cognitive function among community-dwelling older adults. Methods: This prospective cohort study comprised 1213 adults who had two or more waves of BP measurements as part of the China Health and Nutrition Survey from 1991, up to their first cognitive tests, and completed a cognitive screening test at two or more waves in 1997, 2000 or 2004. Mean (SD) age at first cognitive test was 64 (6) y. Outcomes were repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), standardized composite cognitive and verbal memory scores (standardized units [SU]). Visit-to visit BP variability was expressed as the standard deviation [SD] or as the variation independent of mean (SD/mean^x, with x derived from curve fitting) in BP measures obtained at a mean interval of 3.6 years. Multivariable-adjusted linear mixed-effects models were used to determine the association of changes in cognitive scores with visit-to visit BP variability. Results: Higher visit-to-visit variability in systolic BP, but not mean systolic BP, was associated with a faster decline of cognitive function (adjusted mean difference [95% CI] for high vs. low tertile of SD in variability (Figure): global score -0.23 points/y [-0.41 to -0.04], composite scores -0.029 SU/y [-0.056 to -0.002] and verbal memory -0.044 SU/y [-0.075 to -0.012]). Higher visit-to-visit variability in diastolic BP was associated with a faster decline of global cognitive function only among adults 55-64 years, independent of mean diastolic BP. Conclusion: Higher long-term BP visit-to-visit variability predicted a faster rate of cognitive decline among older adults.

Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer’s Disease

2019 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Timo Grimmer ◽  
Oliver Goldhardt ◽  
Igor Yakushev ◽  
Marion Ortner ◽  
Christian Sorg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Pittsburgh Compound B ◽  
Positron Emission ◽  
Amyloid Load ◽  
Alzheimer’S Pathology

Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

scholarly journals Repetitive Negative Thinking is associated with Subjective Cognitive Decline in older adults: a cross-sectional study

2020 ◽  
Author(s):  
Marco Schlosser ◽  
Harriet Demnitz-King ◽  
Tim Whitfield ◽  
Miranka Wirth ◽  
Natalie L. Marchant
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Repetitive Negative Thinking ◽  
Cross Sectional ◽  
Negative Thinking ◽  
Memory Complaints ◽  
Dementia Risk ◽  
Perceived Cognitive Function

Abstract Background: In the absence of a cure or effective treatment for dementia, attention has shifted towards identifying risk factors for prevention. Subjective Cognitive Decline (SCD) describes self-perceived worsening of cognition despite unimpaired performance on neuropsychological tests. SCD has been associated with an increased dementia risk and steeper memory decline. Repetitive negative thinking (RNT) is a transdiagnostic process that manifests across several mental health disorders associated with increased vulnerability to dementia. RNT has thus been proposed as a candidate marker of risk for dementia and, relatedly, could contribute to the manifestation of SCD. We aimed to investigate the relationship between SCD and RNT alongside other proposed psychological risk/protective factors for dementia and cognitive decline. Methods: In a cross-sectional online survey, 491 older adults (mean=64.9 years, SD=4.2; 63.1% female) completed measures of RNT, personality traits, purpose in life, worry, rumination, and meditation practice. SCD was assessed continuously via self-perceived cognitive function (Neuro-QoL) and categorically via endorsement (yes/no) of memory complaints. Regression models, using a stepwise backwards elimination, were built to assess associations between SCD, demographics, and all risk/protective factors.Results: A total of 24.2% of participants reported memory complaints. In the final prediction models, RNT was the only psychological variable associated with lower self-perceived cognitive function and with a higher likelihood of memory complaints. Conclusions: This study empirically corroborates the theoretical relationship between SCD and RNT. Longitudinal studies are needed to establish whether RNT is a prodromal symptom or an independent risk factor, and whether RNT can be a promising construct for future research on SCD and dementia risk.

scholarly journals Neighborhood Environments and Cognitive Decline in Middle and Old Age in China: Gender and Age Variations

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 246-247
Author(s):  
Ye Luo ◽  
Xi Pan ◽  
Lingling Zhang
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Old Age ◽  
Cross Sectional ◽  
Employment Service ◽  
Age Variations ◽  
Gender And Age ◽  
Longitudinal Effects ◽  
Neighborhood Environments ◽  
The Cross

Abstract Older adults are more vulnerable to neighborhood physical and social conditions due to longer exposure, increased vulnerability, changing spatial use, and a greater reliance on access to community sources of integration. Previous research has demonstrated an association between neighborhood environments and cognitive function in older adults. However, most studies were cross-sectional, focused on western countries, and did not examine potential moderating factors. This study examined gender and age variations in the relationship between neighborhood environments and cognitive decline in middle and old age in a developing country that is experiencing rapid population aging and rising prevalence of Alzheimer’s disease and related dementias. Using data from a nationally representative sample of adults aged 45 years and older from the three waves of China Health and Retirement Longitudinal Study (CHARLS 2011-2015), this study estimated multilevel growth curve models for the effects of neighborhood environments on cognitive decline separately for men and women and for those aged 45 to 64 and those aged 65 and above. It showed that the cross-sectional effect of outdoor facility and longitudinal effect of handicapped access were more significant for men, but the cross-sectional effect of community social participation and longitudinal effects of raining days, number of disasters, employment service, and community SES were more significant for women. The cross-sectional effect of infrastructure advantages and longitudinal effects of employment service and old age income support were more significant for adults aged 65 and over. These findings suggest that community-level interventions may be more beneficial for older women.

scholarly journals Dual-task gait speed and mobility are positively associated with declarative memory

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 879-879
Author(s):  
Michelle Gray ◽  
Sally Paulson ◽  
Joshua Gills ◽  
Erica Madero ◽  
Jennifer Myers ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Physical Function ◽  
Sex Education ◽  
Dual Task ◽  
Declarative Memory ◽  
Peak Velocity ◽  
Paired Comparison ◽  
Community Dwelling ◽  
Cognitive Testing

Abstract In the US, it is not recommended to perform routine screening assessments for cognitive function or impairment among older adults, due to the lack of effective pharmacological treatments. These common practices result in delayed identification and treatments for slowing cognitive decline progression. Thus, the purpose of the present investigation was to determine the ability to predict cognition from common measures of physical function. Seventy-five community-dwelling older adults (80.7±5.4 years) completed physical function and cognitive assessments. Physical function was assessed using the Short Physical Performance Battery (SPPB), peak velocity during a power sit-to-stand task, and dual-task walking test. Cognition (declarative memory) was assessed using a validated Visual Paired Comparison test. 38% of the variance in cognition was accounted for by the predictor variables (age, sex, education, SPPB, dual-task, peak velocity). Significant predictors included dual-task walking (p = .03), SPPB (p = .02), and education (p = .02). For each 1 second faster during the dual-task performance, cognition increased by 4 percentile units. Likewise, each 1 unit increase in SPPB resulted in an increase of 4 percentile points in cognition. The results indicate more than a third of the variance in declarative memory can be predicted by commonly assessed measures of physical function. This information is useful when identifying older adults that may have cognitive impairment before overt signs are realized. With the lack of recommended cognitive testing, using physical function declines to identify possible cognitive decline is promising. These results are preliminary in nature and longitudinal determination is warranted.

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