scholarly journals Spatial Extent of Amyloid-β Levels and Associations with Alzheimer’s Disease Biomarkers

2021 ◽  
Author(s):  
Hazal Ozlen ◽  
Alexa Pichet Binette ◽  
Theresa Köbe ◽  
Pierre-Francois Meyer ◽  
John Breitner ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Gaussian Mixture Models ◽  
Amyloid Β ◽  
Gaussian Mixture ◽  
Brain Regions ◽  
Spatial Extent ◽  
Positron Emission ◽  
Tau Pet

Abstract Objective: To investigate the biological and clinical correlates of Aβ spatial extent deposition levels in cognitively unimpaired older adults.Methods: We included cognitively unimpaired older adults from three cohorts, totalling 529 participants (PREVENT-AD, n=129; ADNI, n=400 and HABS, n=288) who underwent Aβ positron emission tomography (PET). We used Gaussian-mixture models to identify region-specific thresholds of Aβ positivity in seven brain regions prone to early Aβ accumulation. Individuals were classified as having “widespread” Aβ deposition if they were positive in all seven regions, “regional” Aβ deposition if they were positive in one to six regions, or Aβ negative if negative in all regions. We compared demographics, genetics, tau-PET binding, and cognitive performance and decline between the three groups.Results: In all cohorts, most participants with regional Aβ-PET binding did not meet the cohort-specific criteria for Aβ-positivity (79% for PREVENT-AD, 57% for ADNI, and 100% for HABS). Regional Aβ groups had normal baseline cognition and relatively normal tau-PET binding, but a greater proportion of APOE ε4 carriers, decreased CSF Aβ1-42 levels, and greater amount of longitudinal Aβ-PET binding accumulation (only available in ADNI and HABS) when compared with the Negative Aβ groups. Widespread Aβ groups had lower baseline cognitive performance (PREVENT-AD only), faster cognitive decline (all cohorts) and greater amount of longitudinal tau binding than the other groups (only available in ADNI and HABS). Conclusions: Individuals with regional Aβ deposition might be the best candidate for preventive trials since they do not yet have widespread tau and cognitive decline. Widespread levels of Aβ seem to be needed for tau spreading.

scholarly journals Characterization of Alzheimer’s tau biomarker discordance using plasma, CSF, and PET

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yu Guo ◽  
◽  
Yu-Yuan Huang ◽  
Xue-Ning Shen ◽  
Shi-Dong Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Braak Stage ◽  
Positron Emission ◽  
Tau Pet

Abstract Background We aimed to investigate the tau biomarker discrepancies of Alzheimer’s disease (AD) using plasma tau phosphorylated at threonine 181 (p-tau181), cerebrospinal fluid (CSF) p-tau181, and AV1451 positron emission tomography (PET). Methods In the Alzheimer’s Disease Neuroimaging Initiative, 724 non-demented participants were categorized into plasma/CSF and plasma/PET groups. Demographic and clinical variables, amyloid-β (Aβ) burden, flortaucipir-PET binding in Braak regions of interest (ROIs), longitudinal changes in clinical outcomes, and conversion risk were compared. Results Across different tau biomarker groups, the proportion of participants with a discordant profile varied (plasma+/CSF− 15.6%, plasma−/CSF+ 15.3%, plasma+/PET− 22.4%, and plasma−/PET+ 6.1%). Within the plasma/CSF categories, we found an increase from concordant-negative to discordant to concordant-positive in the frequency of Aβ pathology or cognitive impairment, rates of cognitive decline, and risk of cognitive conversion. However, the two discordant categories (plasma+/CSF− and plasma−/CSF+) showed comparable performances, resulting in similarly reduced cognitive capacities. Regarding plasma/PET categories, as expected, PET-positive individuals had increased Aβ burden, elevated flortaucipir retention in Braak ROIs, and accelerated cognitive deterioration than concordant-negative persons. Noteworthy, discordant participants with normal PET exhibited reduced flortaucipir uptake in Braak stage ROIs and slower rates of cognitive decline, relative to those PET-positive. Therefore, individuals with PET abnormality appeared to have advanced tau pathological changes and poorer cognitive function, regardless of the plasma status. Furthermore, these results were found only in individuals with Aβ pathology. Conclusions Our results indicate that plasma and CSF p-tau181 abnormalities associated with amyloidosis occur simultaneously in the progression of AD pathogenesis and related cognitive decline, before tau-PET turns positive.

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.

scholarly journals The relationship between memory complaints and age in normal aging

2009 ◽  
Vol 3 (2) ◽  
pp. 94-100 ◽  
Author(s):  
Thaís Bento Lima-Silva ◽  
Mônica Sanches Yassuda
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Digit Span ◽  
Normal Aging ◽  
Screening Tests ◽  
Memory Complaint ◽  
Memory Complaints ◽  
The Impact ◽  
The Relationship

Abstract Normal aging can be characterized by a gradual decline in some cognitive functions, such as memory. Memory complaints are common among older adults, and may indicate depression, anxiety, or cognitive decline. Objectives: To investigate the association between memory complaints and age in cognitively unimpaired older adults, and the relationship between memory complaints and memory performance. Methods: Cognitive screening tests as well as memory complaint questionnaires validated for the Brazilian population were used: the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Memory Complaint Questionnaire (MAC-Q), Memory test of 18 pictures, Forward and Backward Digit Span (WAIS-III). Fifty seven regular members of the SESC social club participated (50 women), having a mean age of 71.4 years, and 4 to 8 years of education - 34 from 4 to 7 years and 23 with 8 years of education. Results: Results revealed no significant association between cognitive complaints and age or cognitive performance. Older participants in this sample did not show worse performance or a higher level of complaints. There was no significant association between age and GDS scores. Conclusions: The studied sample constitutes a particular group of older adults whose participation in activities may be protecting them from cognitive decline, thus highlighting the impact of lifestyle on cognitive performance during the aging process.

scholarly journals Trait mindfulness is associated with less amyloid, tau, and cognitive decline in individuals at risk for Alzheimer's disease

2021 ◽  
Author(s):  
Cherie Strikwerda-Brown ◽  
Hazal Ozlen ◽  
Alexa Pichet Binette ◽  
Marianne Chapleau ◽  
Natalie Marchant ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Decline ◽  
Protective Factor ◽  
Present Moment ◽  
Trait Mindfulness ◽  
Cognitive Assessments ◽  
Positron Emission

Mindfulness, defined as the ability to engage in non-judgmental awareness of the present moment, has been associated with an array of health benefits. Mindfulness may also represent a protective factor for Alzheimer's disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk of AD dementia. Measures of trait mindfulness, longitudinal cognitive assessments, and AB- and tau- positron emission tomography (PET) scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and (1) cognitive decline, (2) AB, and (3) tau. Higher levels of trait mindfulness, particularly mindful nonjudgment, were associated with less cognitive decline, AB, and tau. Trait mindfulness may represent a psychological protective factor for AD dementia.

Neurobiological findings associated with high cognitive performance in older adults: a systematic review

2018 ◽  
Vol 30 (12) ◽  
pp. 1813-1825 ◽  
Author(s):  
Wyllians Vendramini Borelli ◽  
Lucas Porcello Schilling ◽  
Graciane Radaelli ◽  
Luciana Borges Ferreira ◽  
Leonardo Pisani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Cognitive Performance ◽  
Anterior Cingulate ◽  
Control Group ◽  
High Performing ◽  
High Performers ◽  
Positron Emission ◽  
Definition Of ◽  
Molecular Brain

ABSTRACTObjectives:to perform a comprehensive literature review of studies on older adults with exceptional cognitive performance.Design:We performed a systematic review using two major databases (MEDLINE and Web of Science) from January 2002 to November 2017.Results:Quantitative analysis included nine of 4,457 studies and revealed that high-performing older adults have global preservation of the cortex, especially the anterior cingulate region, and hippocampal volumes larger than normal agers. Histological analysis of this group also exhibited decreased amyloid burden and neurofibrillary tangles compared to cognitively normal older controls. High performers that maintained memory ability after three years showed reduced amyloid positron emission tomography at baseline compared with high performers that declined. A single study on blood plasma found a set of 12 metabolites predicting memory maintenance of this group.Conclusion:Structural and molecular brain preservation of older adults with high cognitive performance may be associated with brain maintenance. The operationalized definition of high-performing older adults must be carefully addressed using appropriate age cut-off and cognitive evaluation, including memory and non-memory tests. Further studies with a longitudinal approach that include a younger control group are essential.

scholarly journals Efficacy of tablet-based applications for mental training in preserving cognitive abilities of older adults

ABOUTOPEN ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 24-30
Author(s):  
Marcello Maria Turconi ◽  
Filomena Vella ◽  
Francesco Mosetti
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Cognitive Abilities ◽  
Cognitive Test ◽  
Mental Training ◽  
Versus Group ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background and aims: Nonpathological, age-related cognitive decline is among the most feared consequences of aging. Evidence suggests that the continued use of mental abilities can slow down cognitive decline. We developed two tablet-based applications for the mental training (ElasticaMente) and social interaction/entertainment (iNonni) of older adults. The aim of this study was to evaluate their effect on cognitive performance.Materials and methods: This was an exploratory study of 8 months duration. Sixty healthy residents of a senior community center aged ≥60 years were recruited and divided into three groups: participants in Groups 1 and 2 received a tablet with ElasticaMente and iNonni (Group 1, n = 20) or with iNonni only (Group 2, n = 20); participants in Group 3 (n = 20) did not receive any tablet. Participants in Groups 1 and 2 were instructed to use the applications three times a week (each session ~45 minutes). Cognitive performance was assessed at baseline (T0) and after 8 months (T1) using a battery of six validated tests.Results: In Group 1, cognitive test scores remained consistently stable from T0 to T1, suggesting maintenance of cognitive abilities. In contrast, in Groups 2 and 3, scores worsened from T0 to T1 across all tests. Comparison of the changes from T0 to T1 revealed statistical significance for Group 1 versus Group 3, but not for Group 1 versus Group 2 and Group 2 versus Group 3.Conclusion: The 8 months use of the applications ElasticaMente and iNonni was associated with a significant benefit in terms of preserved cognitive performance compared with no tablet-based activity. The potential contribution of ElasticaMente to the attenuation of cognitive decline should be further investigated.

scholarly journals Neurophysiological signatures in Alzheimer’s disease are distinctly associated with TAU, amyloid-β accumulation, and cognitive decline

2020 ◽  
Vol 12 (534) ◽  
pp. eaaz4069 ◽  
Author(s):  
Kamalini G. Ranasinghe ◽  
Jungho Cha ◽  
Leonardo Iaccarino ◽  
Leighton B. Hinkley ◽  
Alexander J. Beagle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Tracer Uptake ◽  
Therapeutic Approaches ◽  
Regional Patterns ◽  
Positron Emission ◽  
Network Synchrony ◽  
Network Disruptions

Neural synchrony is intricately balanced in the normal resting brain but becomes altered in Alzheimer’s disease (AD). To determine the neurophysiological manifestations associated with molecular biomarkers of AD neuropathology, in patients with AD, we used magnetoencephalographic imaging (MEGI) and positron emission tomography with amyloid-beta (Aβ) and TAU tracers. We found that alpha oscillations (8 to 12 Hz) were hyposynchronous in occipital and posterior temporoparietal cortices, whereas delta-theta oscillations (2 to 8 Hz) were hypersynchronous in frontal and anterior temporoparietal cortices, in patients with AD compared to age-matched controls. Regional patterns of alpha hyposynchrony were unique in each neurobehavioral phenotype of AD, whereas the regional patterns of delta-theta hypersynchrony were similar across the phenotypes. Alpha hyposynchrony strongly colocalized with TAU deposition and was modulated by the degree of TAU tracer uptake. In contrast, delta-theta hypersynchrony colocalized with both TAU and Aβ depositions and was modulated by both TAU and Aβ tracer uptake. Furthermore, alpha hyposynchrony but not delta-theta hypersynchrony was correlated with the degree of global cognitive dysfunction in patients with AD. The current study demonstrates frequency-specific neurophysiological signatures of AD pathophysiology and suggests that neurophysiological measures from MEGI are sensitive indices of network disruptions mediated by TAU and Aβ and associated cognitive decline. These findings facilitate the pursuit of novel therapeutic approaches toward normalizing network synchrony in AD.

scholarly journals Planning and optimising a digital intervention to reduce older adults’ cognitive decline

2020 ◽  
Author(s):  
Rosie Essery ◽  
Sebastien Pollet ◽  
Kirsten A. Smith ◽  
Fiona Mowbray ◽  
Joanna Slodkowska-Barabasz ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Development Process ◽  
Qualitative Interviews ◽  
Intervention Development ◽  
Dementia Prevalence ◽  
Scoping Reviews ◽  
Intervention Content ◽  
Intervention Planning

Abstract Background By 2050 worldwide dementia prevalence is expected to triple, rising to 152 million. Affordable, scalable interventions are required to support protective behaviours such as physical activity, cognitive training and healthy eating. This paper outlines the development of ‘Active Brains’: a multi-domain digital behaviour change intervention to reduce cognitive decline amongst older adults, and key findings arising from this process. Methods A theory-, evidence- and person-based approach to intervention development was undertaken. Scoping reviews and behavioural analysis contributed to intervention planning. Optimisation involved qualitative interviews with 52 older adults with higher and lower cognitive performance scores. Data were analysed thematically and informed changes. Results The development process synthesised findings from planning and optimisation activities. Scoping reviews and qualitative interviews suggested that the same intervention content should be suitable for individuals with higher and lower cognitive performance. Qualitative findings revealed that maintaining independence and enjoyment motivated engagement in intervention-targeted behaviours, whereas managing ill health was a potential barrier. Social support for engaging in such activities could provide motivation, but was not desirable for all. These findings informed development of highly acceptable intervention content and functionality for target users. Conclusions A digitally-delivered intervention with minimal support appears acceptable and potentially engaging to older adults with higher and lower levels of cognitive performance. As well as informing our own intervention, the insights obtained through our development process may be useful for others working with, and developing interventions for, older adults and/or those with cognitive impairment.

scholarly journals Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial

2020 ◽  
Vol 78 (3) ◽  
pp. 989-1010
Author(s):  
Gary E. Gibson ◽  
José A. Luchsinger ◽  
Rosanna Cirio ◽  
Huanlian Chen ◽  
Jessica Franchino-Elder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Placebo Group ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Positron Emission

Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOE ɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

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