A-4 Cerebrospinal Fluid and Plasma Neurofilament Light in Relation to Longitudinal Objective and Subjective Cognitive Decline in Older Adults

2021 ◽  
Vol 36 (6) ◽  
pp. 1043-1043
Author(s):  
Natalie A Thwaites ◽  
Omair A Khan ◽  
Dandan Liu ◽  
Marilyn Steinbach ◽  
Camdyn Gilbert ◽  
...  

Abstract Objective Cerebrospinal fluid (CSF) and plasma neurofilament light (NFL) concentrations were assessed in relation to longitudinal objective and subjective cognitive outcomes in older adults ranging from normal cognition to mild cognitive impairment. Interactive effects were assessed for apolipoprotein E ϵ4 (APOE4) carriership, a strong genetic risk factor for Alzheimer’s disease and molecular moderator of vascular disease. Method Vanderbilt Memory & Aging Project participants (CSF n = 149, 72 ± 6 years; plasma n = 333, 73 ± 7 years) underwent fasting blood draw and lumbar puncture at baseline for NFL quantification. Serial neuropsychological assessments and subjective cognitive decline (SCD) questionnaires were completed at 18-month increments. Linear mixed effects regression models adjusted for age, sex, race/ethnicity, education, APOE4 carriership (for main effect models), and depressed mood. NFL x APOE4 interaction terms were used as predictors in follow-up models. Results CSF NFL predicted steeper declines in an executive functioning composite score (β = −0.0001, p = 0.001) and WAIS-IV Coding (β = −0.001, p = 0.001). An APOE4 interaction was present for executive functioning (β = −0.0002, p = 0.005) such that CSF NFL associations with longitudinal decline were stronger among APOE4+ participants. Plasma NFL predicted worsening SCD (β = 0.27, p = 0.002) and objective cognitive decline across all domains (p-values <0.05), with multiple APOE4 interactions (p-values <0.05) suggesting stronger associations with objective cognitive decline among APOE4+ participants. Conclusions Both CSF and plasma NFL detect neuropathology associated with cognitive decline among non-demented older adults, especially among APOE4 carriers. Findings further support the value of SCD as reflecting neurodegenerative changes associated with accelerated cognitive aging.

2021 ◽  
Vol 36 (6) ◽  
pp. 1047-1047
Author(s):  
Camdyn Gilbert ◽  
Marilyn Steinbach ◽  
Omair Kahn ◽  
Dandan Liu ◽  
Natalie Thwaites ◽  
...  

Abstract Objective Neurogranin is a postsynaptic protein associated with declining memory and executive functioning in Alzheimer’s disease (ad). While previous research suggests neurogranin concentrations in ad are higher in women, it is unclear whether sex differences exist in earlier disease stages or predict different cognitive outcomes. This study investigates cerebrospinal fluid (CSF) neurogranin in relation to longitudinal cognitive decline in older adults ranging from normal cognition to mild cognitive impairment, assessing for interactions by sex. Method Vanderbilt Memory & Aging Project participants completed baseline fasting lumbar puncture (n = 155, 73 ± 8 years) for neurogranin quantification and serial neuropsychological assessments at 18-month intervals. Linear mixed effect regression adjusting for age, sex (for main effect models), race/ethnicity, education, cognitive diagnosis, depressed mood, and APOE-ε4 carrier status. Results CSF neurogranin predicted worse cognitive decline across multiple domains (p-values <0.05). Sex interactions existed for Boston Naming Test (β = −0.007, p = 0.001), WAIS-IV Coding (β = −0.01, p = 0.02), Hooper Visual Orientation Test (β = −0.005, p = 0.02), and Category (animals) Fluency (β = −0.005, p = 0.048) wherein CSF neurogranin predicted worse decline among women (p-values≤0.03) but not men (p-values≥0.36). Conclusion Results suggest that among nondemented older adults, CSF neurogranin predicts worse longitudinal cognitive decline in women but not in men. Further research is needed to elucidate underlying mechanisms that may account for these differences, such as possible sex hormone factors. These findings highlight the importance of pursuing individualized prevention and treatment approaches to combat accelerated cognitive aging that take into account the possibility of multiple, divergent disease pathways preceding ad and dementia among various demographic groups.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 361-361
Author(s):  
Claudia Jacova ◽  
Samantha Smith ◽  
Frank Robertson

Abstract Subjective cognitive decline (SCD) is a construct of high interest in aging and dementia because individuals endorsing it are at higher risk of developing cognitive problems. It is unclear how individuals arrive at the judgement that they have SCD. Here we aimed to understand which SCD symptoms give rise to the perception of decline as older adults age. Community-dwelling adults (N=494, mean age=63.6, SD=5.44), completed the Subjective Cognitive Decline Questionnaire (SCD-Q) online, using an online crowdsourcing site. The SCD-Q consists of one global question regarding self-perceived decline (yes/no) and 24 questions about everyday functioning which we utilized to form a memory, language, and executive functioning domain score, higher for greater perceived decline. Logistic regression revealed that memory and language domains predicted the likelihood of endorsing SCD for adults aged >64 (Memory: OR=1.76, CI=1.47-2.05; Language: OR=1.66, CI=1.30-2.02). Only the memory domain predicted the likelihood of endorsing SCD for adults <63 (OR=2.69, CI=2.35-3.02). Executive functioning domain scores did not play a role in the relationship between SCD likelihood in either age group. The higher the self-perceived memory or language decline, the more likely older adults are to conclude they have SCD. Our results suggest there is an age-related trajectory in how people evaluate their cognition, with younger people only considering memory and older people considering both memory and language. Clinicians should be aware of this trajectory when examining patients with SCD. Executive functions should be specifically queried because they may not emerge from older adults’ self-reported cognitive problems.


Author(s):  
Yvonne Rogalski ◽  
Muriel Quintana

The population of older adults is rapidly increasing, as is the number and type of products and interventions proposed to prevent or reduce the risk of age-related cognitive decline. Advocacy and prevention are part of the American Speech-Language-Hearing Association’s (ASHA’s) scope of practice documents, and speech-language pathologists must have basic awareness of the evidence contributing to healthy cognitive aging. In this article, we provide a brief overview outlining the evidence on activity engagement and its effects on cognition in older adults. We explore the current evidence around the activities of eating and drinking with a discussion on the potential benefits of omega-3 fatty acids, polyphenols, alcohol, and coffee. We investigate the evidence on the hypothesized neuroprotective effects of social activity, the evidence on computerized cognitive training, and the emerging behavioral and neuroimaging evidence on physical activity. We conclude that actively aging using a combination of several strategies may be our best line of defense against cognitive decline.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 293-294
Author(s):  
Moriah Splonskowski ◽  
Holly Cooke ◽  
Claudia Jacova

Abstract Home-based cognitive assessment (HBCA) services are emerging as a convenient alternative to in-clinic cognitive assessment and may aid in mitigating barriers to detecting cognitive impairment (CI). It is unknown which older adults would be likely to participate in HBCA. Here we investigated the role of age and Subjective Cognitive Decline (SCD). SCD has demonstrated an increased risk for progression to CI/dementia. A nation-wide community-dwelling sample of 494 adults age 50+ were recruited via Amazon Mechanical Turk to complete an online survey assessing perceptions around HBCA and SCD. Our sample was 91.9% White and 66.8% female. It consisted of 174 respondents aged 50-60, 265 aged 61- 70, and 55 aged 71-79. Age groups were comparable with respect to their acceptance of cognitive assessment (Range 4-20, higher score=higher acceptance, 7.9±3.3, 8.15±3.2, 8.05±3.43) and SCD-Q total (43.1±5.8, 43.2±5.7, 43.3±5.7). Correlation analysis revealed a relationship between SCD-QSCD total and perceived likelihood of participation in HBCA for those ages 61-70 (r(263) = .222 p = .000), but not for ages 50-60 or 71-79 (r(172) = .102 p = .152; r(53) = -.102 p = .458). Our findings suggest that SCD influences the likelihood of participation in HBCA for older adults’ transitioning to old age (61-70). Findings show that for adults transitioning into old age (61-70), perceived cognitive state influences their likelihood of participation in HBCA. Importantly, concerns about CI/dementia may generate more favorable perceptions of HBCA for this group.


2021 ◽  
pp. 1-14
Author(s):  
Nikki L. Hill ◽  
Sakshi Bhargava ◽  
Emily Bratlee-Whitaker ◽  
Jennifer R. Turner ◽  
Monique J. Brown ◽  
...  

Background: Subjective cognitive decline (SCD) may be an early indicator of cognitive impairment, but depressive symptoms can confound this relationship. Associations may be influenced by differences between individuals (i.e., between-persons) or how each individual changes in their experiences over time (i.e., within-persons). Objective: We examined depressive symptoms as a mediator of the between- and within-person associations of SCD and objective memory in older adults. Methods: Coordinated analyses were conducted across four datasets drawn from large longitudinal studies. Samples (range: n = 1,889 to n = 15,841) included participants 65 years of age or older with no dementia at baseline. We used multilevel structural equation modeling to examine the mediation of SCD and objective memory through depressive symptoms, as well as direct relationships among SCD, objective memory, and depressive symptoms. Results: Older adults who were more likely to report SCD had lower objective memory on average (between-person associations), and depressive symptoms partially mediated this relationship in three of four datasets. However, changes in depressive symptoms did not mediate the relationship between reports of SCD and declines in objective memory in three of four datasets (within-person associations). Conclusion: Individual differences in depressive symptoms, and not changes in an individual’s depressive symptoms over time, partially explain the link between SCD and objective memory. Older adults with SCD and depressive symptoms may be at greater risk for poor cognitive outcomes. Future research should explore how perceived changes in memory affect other aspects of psychological well-being, and how these relationships influence cognitive decline and Alzheimer’s disease risk.


2020 ◽  
Vol 77 (2) ◽  
pp. 715-732
Author(s):  
Eleni Poptsi ◽  
Despina Moraitou ◽  
Emmanouil Tsardoulias ◽  
Andreas L. Symeonidisd ◽  
Magda Tsolaki

Background: The early diagnosis of neurocognitive disorders before the symptoms’ onset is the ultimate goal of the scientific community. REMEDES for Alzheimer (R4Alz) is a battery, designed for assessing cognitive control abilities in people with minor and major neurocognitive disorders. Objective: To investigate whether the R4Alz battery’s tasks differentiate subjective cognitive decline (SCD) from cognitively healthy adults (CHA) and mild cognitive impairment (MCI). Methods: The R4Alz battery was administered to 175 Greek adults, categorized in five groups a) healthy young adults (HYA; n = 42), b) healthy middle-aged adults (HMaA; n = 33), c) healthy older adults (HOA; n = 14), d) community-dwelling older adults with SCD (n = 34), and e) people with MCI (n = 52). Results: Between the seven R4Alz subtasks, four showcased the best results for differentiating HOA from SCD: the working memory updating (WMCUT-S3), the inhibition and switching subtask (ICT/RST-S1&S2), the failure sets (FS) of the ICT/RST-S1&S2, and the cognitive flexibility subtask (ICT/RST-S3). The total score of the four R4Alz subtasks (R4AlzTot4) leads to an excellent discrimination among SCD and healthy adulthood, and to fare discrimination among SCD and MCI. Conclusion: The R4Alz battery is a novel approach regarding the neuropsychological assessment of people with SCD, since it can very well assist toward discriminating SCD from HOA. The R4Alz is able to measure decline of specific cognitive control abilities - namely of working memory updating, and complex executive functions - which seem to be the neuropsychological substrate of cognitive complaints in community dwelling adults of advancing age.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S94-S94 ◽  
Author(s):  
Erik L Knight ◽  
Ryan Giuliano ◽  
Sean Shank ◽  
Megan Clarke ◽  
David M Almeida

Abstract The two branches of the autonomic nervous system (ANS) have been individually linked to age-related changes in cognitive functioning: The parasympathetic nervous system (PNS) is thought to support healthy cognitive aging, whereas the sympathetic nervous system (SNS) has been linked to heightened cognitive decline. Despite these separate findings and despite the integrative nature of the ANS, little work has examined the two branches simultaneously to better understand their interactive effects on age-related cognitive changes. We examined cognitive change in two waves of the MIDUS cognitive project and indexed PNS and SNS activity from heart rate variability and epinephrine levels (respectively) from the MIDUS biomarker project (n = 764, 56% female, mean age = 54.1 years). Our findings indicate that higher PNS levels attenuate cognitive decline, but only among individuals with low SNS levels; at higher SNS levels, the beneficial effects of the PNS are blocked. Further, lower PNS levels can be somewhat compensated for by increased SNS levels. This pattern was most robust among individuals transitioning to mid-life (i.e., 35-40 years old at the initial cognitive test). These results suggest that interventions targeting the ANS as a modifiable factor in cognitive aging should consider both ANS branch’s effects simultaneously, particularly in the early stages of midlife.


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