Choice response time (RT) increases linearly with increasing information uncertainty, which can be represented externally or internally. Using a card-sorting task, we previously showed that Alzheimer’s disease (AD) dementia patients were more impaired relative to cognitively normal older adults (CN) under conditions that manipulated internally cued rather than externally driven uncertainty, but this study was limited by a between-subjects design that prevented us from directly comparing the two uncertainty conditions. The objective of this study was to assess internally cued and externally driven cued uncertainty representations in CN and mild cognitive impairment (MCI) patients.

Older participants (age > 60 years; N=49 CN, N=33 MCI patients) completed a card-sorting task that separately manipulated externally cued uncertainty (i.e., the number of sorting piles with equal probability of each stimulus type) or internally cued uncertainty (i.e., the probability of each stimulus type with fixed number of sorting piles) at three different uncertainty loads (low, medium, high). Exploratory analyses separated MCI patients by etiology into possible/probable cortical neurodegenerative process (i.e., AD, frontotemporal dementia; N=13) or nonneurodegenerative process (i.e., vascular, psychiatric, sleep, medication effect; N=20).

CN and MCI patients maintained a high level of accuracy on both tasks (M accuracy > .94 across conditions). MCI patients performed more slowly than CN on the externally and internally cued tasks, and both groups showed a significant positive association between uncertainty load and RT (p’s < .05). There was a group x load x uncertainty condition interaction (p = .05). For CNs, the slope of the linear association between load and RT was significantly steeper in the externally cued compared to internally cued condition. For MCI patients in contrast, RTs increased with load to a similar degree in both conditions. Exploratory analyses showed the MCI-neurodegenerative patients were significantly slower than MCI-nondegenerative and CN (p < .001). While the group x load x condition interaction was significant when comparing all three groups (p < .05), this was driven by the differences between CN and MCI patients described above; the MCI-neurodegenerative and non-neurodegenerative groups did not significantly differ in the strength of the RT-load association between the externally or internally cued conditions.

Overall, CN participants showed greater RT slowing with increasing load of externally driven than internally cued uncertainty. Though they were slower than CNs, MCI patients (even those with a possible/probable cortical neurodegenerative condition) were able to accurately perform an internally cued uncertainty task and did not show differential slowing compared to an externally driven task. This provides preliminary evidence that internal representations of probabilistic information are intact in patients with MCI due to a neurodegenerative condition, meaning they may not depend on cortical processes. Future work will increase the sample sizes of the MCI-neurodegenerative and non-degenerative groups.

Historically, psychiatric conditions and neurodegenerative diseases have been considered differential diagnoses in older adults with cognitive impairment. However, recent evidence has shown that neuropsychiatric symptoms may be prodromal for neurodegenerative disease. Subjective Cognitive Decline (SCD) is a potential marker for pre-clinical Alzheimer’s Disease (AD) that is frequently related to mood disturbances. Delineating the relationship between neuropsychiatric symptoms, SCD, and cognitive impairment will help to define both the independent and combined utility of SCD and neuropsychiatric symptoms as markers of preclinical AD. This abstract uses the DSM-5 Cross-Cutting Measure (DSM-5 CC), a novel comprehensive screening tool for psychiatric symptoms, to examine the relationship between objective and subjective measures of cognition as they relate to neuropsychiatric symptoms.

27 community dwelling, cognitively diverse older adults (78% female, mean age 71.9 ± 7) were enrolled in the Concerns about Memory Problems (CAMP) study. Inclusion criteria included the expressed concern about memory functioning by participants on a 5-item screener, while exclusion criteria were defined as previous diagnosis of neurodegenerative diseases and/or major stroke. All participants completed neuropsychological testing and study surveys including the DSM-5 CC. Participants completed Level 1 and all Level 2 (L2) forms of the DSM-5 CC. Spearman two-tailed non-parametric correlations and independent samples t-tests were conducted to examine the relationship between the DSM-5 CC and the 5-item subjective cognition screener, as well as the DSM-5 CC and objective cognition results.

Subjective measures of cognition, as measured by answers to the 5-item screening measure, were significantly associated with DSM-5 CC measures. Question 1 on the SCD screener which asks, “Compared to others your age, do you have difficulty with memory or thinking abilities?” was associated with anger (p=.033) and depression (p=.018) L2 forms. Question 3, “Do any difficulties with memory or thinking abilities make it difficult for you to do things in daily life?)” was associated with the L2 forms for somatic symptoms (p=.016) and repetitive thoughts and behaviors (p<.001). Objective measures of cognition from neuropsychological testing also correlated with DSM-5 CC sub-scores. Digits Backwards Length (DBL) correlated with DSM-5 CC Level 1 Sum (r= -.57, p=.002). DBL (r=-.59 p=.001) and Digits Backwards Total Correct (DBTC) (r=-.47, p=.013) associated with somatic symptoms L2 and sleep L2 (DBL: r=,-.45 p=.019; DBTC: r=-.39, p=.044). Category Naming (animals) was also associated with anxiety L2 (r=-.42, p=.030).

Subjective and objective measures of cognition were each related to sub-scores of the DSM-5 CC. Interestingly, the associations were largely non-overlapping. These results highlight the importance of considering a wide range of neuropsychiatric symptoms in the assessment of SCD and cognitive impairment. Findings contribute to the growing body of literature suggesting that neuropsychiatric symptoms should be studied in conjunction with cognitive symptoms among older adults as co-occurring phenomena. Future directions will need to include longitudinal studies that can examine the prodromal nature of SCD and neuropsychiatric symptoms for Alzheimer’s and other neurodegenerative disorders.

Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD). Recent scientific advances show that MCI in PD could also be impacted by neuropsychiatric symptoms (such as apathy, anxiety, depression), dopaminergic deficiency (more striatal denervation associated with MCI) and certain genotypes such as in APOE E4, MAPT H1 or SNCA C/C carriers. We used a python-based random forest machine-learning algorithm (scikit-learn) in order to evaluate the factors that are mostly involved in the MCI conversion over a 5-year follow-up period.

Baseline data of healthy individuals and participants with Parkinson’s disease were extracted from the PPMI dataset. All participants also had the evaluations of their cognitive status, neuropsychiatric symptoms (hallucinations, anxiety, apathy, depression, sleepiness, impulse control disorders and rapid eye movement behaviors), dopaminergic uptake (DaT-Scan) and genetic status (APOE, MAPT and SNCA) at baseline and after 5 years. Baseline demographic (age, sex, education years) and clinical values (duration of disease, age of onset) were also included in the model. The algorithm defined (1) the most important variables in predicting MCI, (2) the threshold values to distinguish “converting” vs. “non-converting” subgroups.

The algorithm showed that (1) age onset of disease, (2) dopaminergic uptake, (3) age, (4) anxiety, and (5) years of education were the most important factors in predicting MCI over 5 years. Among the factors involved in predicting conversion to MCI, a lower number of years of education associated with lower dopaminergic uptake in the right putamen increased the risk of conversion. Individuals with more years of education are at higher risk of conversion if they have symptoms of depression, anxiety, and lower right striatal dopamine uptake. Other factors that were involved in increasing the risk, were the presence of sleepiness and the presence of rapid eye movement disorders. Interestingly, the genetic factors were of negligible importance and were not considered by the algorithm. Finally, the model showed an accuracy of classification of participants (converters vs. non-converters) of 92.53%.

Random forest algorithm shows that (1) depression and anxiety are probably important factors for MCI conversion; (2) years of education influences the conversion; (3) presence of sleepiness and rapid eye movement increases the risk of conversion to MCI. Since the algorithm considers the disease’s age onset, but not the diagnosis of individuals, it would be necessary to generate a model for each group (Healthy on the one hand, Parkinson’s on the other).

The objective of this study is to explore the impact on the mental health of caregivers of people with dementia during the period of mandatory preventive social isolation (ASPO) and to study which of these factors were predictors of caregiver overload.

During the first 3 months of the ASPO (June 2020 to september 2020). A sample of 112 caregivers (75.89% female; age 58.65 ± 14. 30) of patients with dementia from a Memory Center answered, remotely (online or telephone) a survey with the following questionnaires: the Zarit Caregiver Overload Scale (ZBI), Weekly hourly load dedicated to the care of patients with dementia), the use of time in unpaid activities through an activity diary, provided by Argentine National Institute of Statistics and Census (INDEC), the Caregiver Activities Survey (CAS) and the Anxiety, Depression and Stress Scale (DASS-21). These questionnaires evaluate the conditions and characteristics of caregiving tasks and their impact on the caregiver in the context of ASPO. Additionally, it was recorded whether the person with dementia, the caregiver, or persons living with them had had COVID-19.

Descriptively, a disparity in frequency was observed in the gender of caregivers of persons with dementia, i.e., caregiving is inequitably distributed between men (24.11%) and women (75.89%). This difference hinders direct comparison between men and women. A regularized L2 regression was performed for the identification of predictors of caregiver overload identifying the number of caregiving hours (β=0.090), DAS depression (β=0.085), DASS anxiety (β=0.099) DASS stress (β=0.164), fear of Covid (0.141) and lower patient cognitive performance according to MMSE (β=-0.41) and to lesser extent sex as the greatest contributors to patient overload. Additionally, a mediation analysis was performed in which the factors number of caregiving hours (CAS; r= 0.254,r= 0.292,r= 0.252,r= 0.252,r= -0.37), being a primary caregiver and fear of Covid-19 (r= 0.335,r= 0.432,r= 0.402,r= -0.496) were found to be mediators of the effect between anxiety, depression, stress (DASS) and overload (ZBI).

Caregivers of patients with dementia have suffered sequelae such as anxiety, stress, depression, and overload (caregivers’ burden) in the context of the COVID-19 virus spread and during mandatory preventive social isolation. Being a primary caregiver, dedicating more hours to caregiving, and fear of Covid-19 are factors that contribute significantly to caregiver burden and mediate between this burden and mood variables. Public policies to support caregivers and information about the disease could modify these variables and reduce caregiver burden.

A diagnosis of mild cognitive impairment (MCI) requires memory complaint and objective memory impairment. However, some individuals report subjective memory complaints (SMC) despite having intact memory performance, while others demonstrate subtle impairment on memory testing but have no memory complaints; neither case would meet criteria for MCI. This study aimed to compare memory performances over time in individuals who do not meet traditional MCI criteria to those with normal cognition and those who converted to MCI.

Diagnoses for a longitudinal sample from the Texas Alzheimer’s Research and Care Consortium were reviewed by a consensus panel of neuropsychologists and neurologists and reclassified at time of last visit. Diagnostic categories included SMC (i.e., memory complaint but no impairment on testing), objective cognitive impairment but no complaint (Impaired but not MCI), normal control (NC), MCI, and dementia. In this study, 827 participants were divided into 4 groups: 1) NC over 5 visits (n=511, 71% female; 42% Latinx/Hispanic), 2) baseline NC to amnestic MCI (n=62; 63% female; 57% Latinx/Hispanic), 3) SMC at last visit (n=133; 58% female; 70% Latinx/Hispanic), and 4) impaired but not MCI at last visit (n=121; 71% female; 60% Latinx/Hispanic). A memory composite (z-score) was created from the CERAD list-learning task (immediate, delayed, and recognition-discrimination) and Wechsler Memory Scale (Immediate and Delayed Logical Memory and Visual Reproduction) to evaluate memory performance over time. A linear mixed-model adjusting for age, education, sex, ethnicity, and number of APOE e4 alleles evaluated memory performance across 5 visits for the groups. To assess if depression followed a similar course, a linear mixed-model evaluated Geriatric Depression Scale (GDS) scores over time.

At baseline, groups differed by age (F=22.82; p<.001), education (F=8.60; p<.001), MMSE scores (F=9.38; p<.001), GDS-30 scores (F=3.56; p=.015), and memory composites (F=24.29; p<.001). A significant group X time interaction was observed (F=4.83, p<.001). Memory performance improved in both the SMC and the NC groups, remained stable in the impaired but not MCI group, and declined (as expected) in those who converted to amnestic MCI. Depression scores also showed a significant group X time interaction (F=2.43; p=.004), in which the NC to MCI group endorsed slightly more depression symptoms over time, while other groups declined or remained stable.

Memory trajectories in this diverse sample differed across groups. Individuals with SMC but without objective memory impairment and normal controls showed some improvement in memory over time, presumably due to practice effects. Those with subtle memory impairments but no complaint (i.e., did not meet MCI criteria) remained stable and those who converted to amnestic MCI had worse memory across time. The stability of memory performances in the impaired not MCI group suggests these subtle memory inefficiencies may be longstanding or unperceived. However, because our sample achieved retrospective diagnoses of SMC and impaired not MCI, it will be important for future studies to prospectively follow these groups to determine which risk factors may predict progression to MCI and what impact ethnicity may have on these trajectories.

The Biber Figure Learning Test (BFLT) is a serial figure learning assessment previously been shown to be sensitive to various biomarkers of the aging brain. BFLT is an extensive assessment requiring about 30 minutes for administration. In this study, we investigated BFLT’s associations with subjective cognitive decline (SCD), an early marker for preclinical Alzheimer’s Disease (AD), and examined whether alternative BFLT indices could be utilized to considerably shorten the length of assessment without decreasing its sensitivity to SCD.

Participants were 50 cognitively normal older adults (8% Hispanic, 92% Non-Hispanic; 78% White, 16% Black; 64% female; mean age =72.7 (SD =6.2); mean education =17.05 (SD =2.09)). SCD was measured using a 20-item age-anchored dichotomous questionnaire that assessed complaints of cognitive functioning, and the BFLT was administered in full. Pearson correlations were conducted between SCD and BFLT scores including: Trial 1 Learning (T1), Trials 1 to 2 Total Learning (T1T2), Trials 1 to 3 Total Learning (T1T3), Trials 1 to 5 Total Learning (Total Learning), Immediate Recall, Delayed Recall, Proactive Interference (Trial B – Trial 1), Retroactive Interference (Immediate Recall – Trial 5), and Total Discrimination (calculated as [Recognition Total Correct + 0.5]/16) − ([Total False Alarms + 0.5]/31]). A Fishers Exact Test was utilized to compare the correlational strength between SCD and each of the BFLT scores. Lastly, demographically adjusted (age, gender, and education) regression models were conducted to examine SCD as an individual predictor for the various BFLT scores.

SCD was negatively associated with BFLT T1 (r =-0.406, p =0.003), T1T2 (r =-0.331, p =0.019), T1T3 (r =-0.323, p =0.022), Total Learning (r =-0.283, p =0.046), Immediate Recall (r =-0.322, p =0.023), Delayed Recall (r =-0.318, p =0.025), and Retroactive Interference (r =-0.388, p =0.005) and positively associated with Proactive Interference (r =0.308, p =0.029). There was no significant difference in correlational strength between any of these BFLT scores and SCD. Adjusting for demographics, SCD predicted Immediate Recall (B =-0.273, p =0.029), Total Learning (B =- 0.253, p =0.040), T1 (B =-0.412, p =0.002), T1T2 (B =-0.326, p =0.010), T1T3 (B =-0.299, p =0.017), Proactive Interference (B =0.292, p =0.050), and Retroactive Interference (B =- 0.330, p =0.025).

Eight of the nine assessed BFLT scores were strongly correlated with age-anchored SCD and age-anchored SCD predicted seven of the nine assessed BFLT indices when adjusted for demographics. Although additional work is needed, these findings suggest SCD’s sensitivity to changes in visuospatial learning and memory, supporting its use as an early marker for preclinical AD. Likewise, our results suggest that an abbreviated version of the BFLT could be utilized that shortens testing time and reduces participant fatigue without a decrease in clinical relevance. Through ongoing longitudinal work, we hope to further disentangle the relationship between SCD and visuospatial learning and memory as measured through the BFTL and to examine how associations between SCD and the BFLT assessment change over time.

Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.

The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 & 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.

Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.

Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.

US forces used Agent Orange (AO) during the Vietnam War and continued to store/test it at other locations after the war. AO is a powerful herbicide including dioxin, a highly toxic ingredient classified as a human carcinogen. The National Academies of Sciences, Engineering, and Medicine periodically review the literature on the health effects of AO exposure (AOE) and concluded in 2018 that there is sufficient evidence linking AO with a wide range of adverse health outcomes, including neurologic disorders (e.g., Parkinson’s disease). The VA has a list of medical disorders considered presumptive conditions related to AOE. More recently, AOE has been linked to a nearly double risk compared to those without AOE for receiving a dementia diagnosis. To our knowledge, no one has investigated the association of AOE to mild cognitive impairment (MCI), a condition thought to precede dementia.

We examined men in three waves of the Vietnam Era Twin Study of Aging (VETSA). In wave 3, participants self-reported yes/no to the question of whether they ever had prolonged or serious AOE. MCI was diagnosed by the Jak-Bondi approach. Impairment was defined as 2+ tests within a cognitive domain that were more than 1.5 standard deviations below normative means after adjusting for premorbid cognitive ability. In mixed effects models, we tested the effect of AOE on MCI status. Models were adjusted for age, ethnicity, and non-independence within twin pairs.

In wave 3, 12.6% (230) of 1167 participants reported AOE. Those with AOE data had mean ages of 51.1 (wave 1), 56.0 (wave 2), and 61.4 (wave 3). Those with data on both AOE and MCI numbered 861 (wave 1), 900 (wave 2), 1121 (wave 3), and 766 had AOE and MCI at all waves. AOE was significantly related to wave 2 MCI (p < .001), but not to waves 1 and 3 MCI. AOE was significantly associated with the number of time points at which someone met criteria for MCI (p = .011). Analyses were conducted on six cognitive domains used to diagnose MCI, using available participants per wave. At all 3 waves, AOE was significantly associated with lower scores in processing speed (p = .003, p = .004, p = .005, respectively), working memory (p < .001, p = .002, p = .008) and nearly significant at all waves for executive dysfunction (p < .001, p < .001, p = .050). There were two other significant associations [wave 2 memory (p = .038), wave 3 fluency (p = .024)]. The semantic fluency cognitive domain was unrelated to AOE in all waves.

AOE was consistently associated with lower processing speed, working memory, and executive dysfunction in males ages 51-61. It was also associated with the number of time points at which one met criteria for MCI in that age range, and with MCI in the mid-fifties. Findings support the idea of a risk for greater cognitive decline in those exposed to AO earlier in their lives, and with a risk for developing MCI.

Subjective Cognitive Decline (SCD), the perception of deteriorating cognition in the absence of apparent impairment on objective testing, has gained momentum in recent literature as a risk marker for AD. Traditional neuropsychological assessments, while typically inclusive of a word list learning task, often do not include a comparable figure learning task. Growing evidence suggests that nonverbal assessments may be particularly sensitive to the earliest cognitive changes associated with Alzheimer’s disease. The Biber Figure Learning Test (BFLT), a visuospatial analogue to verbal list learning tasks, has been shown to associate with brain-based biomarkers of Alzheimer’s disease (AD; hippocampal volume, amyloid load). This study investigates the utility of the BFLT in capturing SCD above and beyond other cognitive measures sensitive to AD progression.

50 community-dwelling, cognitively normal individuals (78% White, 16% Black, 6% Other; 92% Non-Hispanic; 64% Female; Education M=17.1, SD=2.1; Age M=72.7, SD=6.2) participated in a study of SCD. All participants performed >-1.5 SD on clinical neuropsychological testing including a word list learning task. SCD was assessed using a 20-item scale querying individuals’ perception of difficulty across a range of memory and non-memory abilities in relation to others of the same age. Participants completed the BFLT, Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), Short-Term Memory Binding (STMB), and Face-Name Associative Memory Exam (FNAME), previously established as being sensitive to pre-clinical AD, were examined as predictors of SCD. A multiple regression adjusted for demographics (age, gender, education) was used to investigate the extent to which BFLT Trial 1 (T1) predicted SCD above and beyond these other cognitive measures sensitive to AD progression. Trial 1 of the BFLT was used based on a separate abstract examining which BFLT score was most highly associated with SCD (Kann et al., pending acceptance).

Adjusting for demographics, the present model accounts for 42% of the variance in SCD, while Biber T1 alone accounts for 20% and is the only significant individual predictor of SCD (β=-0.55, p=0.004). In contrast, other variables in the model independently accounted for less than 1% to 4% each (age β=-0.23, p=0.15; gender β=-0.15, p=0.34; education β=0.06, p=0.66; LASSI-L β=-0.11, p=0.55; STMB β=-0.03, p=0.85; FNAME β=-0.10, p=0.64).

The present study demonstrates the usefulness of the first learning trial of the BFLT as an independent predictor of SCD above and beyond other verbal and nonverbal measures sensitive to AD pathology. It also highlights the value of including even one trial of figure learning (< 5 minutes) in both clinical and research assessments seeking to capture cognitive changes which may be the earliest indicators of a neurodegenerative process. Ongoing longitudinal research is examining the predictive utility of the BFLT for future cognitive decline and transition to Mild Cognitive Impairment. Further research should explore the association between Biber T1, specifically, and neuropathological biomarkers of AD to further establish its utility as a portent of AD.

Subjective cognitive decline (SCD) is increasingly being considered one of the earliest clinical signs of Alzheimer’s Disease (AD). Certain characteristics of early life, such as childhood socioeconomic status (SES), have been associated with late life cognitive performance. Here we examine the extent to which childhood SES predicts SCD.

The current sample consisted of 55 healthy older adults (17 Male, 39 Female), aged 51 to 88 (M=73.14, SD=6.23) with a mean education of 16 years (SD=2.1 years). 21.5% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic African American, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, and objective cognitive testing. Childhood SES was assessed using two items. The first item asked the participant to utilize a modified MacArthur Scale of Subjective Social Status to identify where on the ladder they felt their family would have been placed during their childhood relative to others in the United States. This ladder has 10 rungs, with rung 1 associated with being the “worst off” and rung 10 associated with being the “best off”. The second item asked the participant to rate their family’s difficulty paying bills during their childhood. Linear regression models were used to examine the extent to which childhood SES predicted SCD. Models were adjusted for education, referral source (clinical versus non-clinical), and objective cognitive testing. Age and gender were not associated with childhood SES or SCD, and as a result were not adjusted for in these models.

On the MacArthur Scale, 20% of participants placed their family at rung 5, 38.2% placed their families at a rung lower than 5, and 41.8% placed their family at a rung higher than 5. When rating the difficulty their family faced paying bills, 3.6% of participants responded “extremely difficult”, 16.4% responded “very difficult”, 20% responded “somewhat difficult”, 23.6% responded “slightly difficult”, and 36.4% responded “not difficult”. Linear regression models revealed a significant effect of childhood SES on SCD (β=-.29, p=.045, SE=.90; β=-.35, p=.015, SE=1.68).

Childhood SES, measured by subjective social status and family’s difficulty paying the bills in childhood, was predictive of SCD in this study of cognitively healthy adults. This result highlights another characteristic of early life that may shape the path of cognitive aging. The predictive utility of childhood SES for SCD may also provide clinicians and researchers with further insight into the populations that may be more susceptible to experiencing SCD in later life. Future studies should utilize a larger sample size among a population with a greater range of childhood SES, to most accurately capture the effectiveness of childhood SES to predict SCD.

Physical inactivity is associated with a greater risk of frailty, neuropsychiatric symptoms, worse quality of life, and increased risk for Alzheimer’s disease. Little is known about how physical activity engagement of older adults during the COVID-19 pandemic relates to subjective cognitive concerns and management of emotional distress. This study aimed to examine whether there were changes in physical activity during the pandemic in older adults at baseline and 3 months compared to before the pandemic and whether these changes varied based on age, sex, income level, and employment status. Further, we examined whether individuals who reported engaging in less physical activity experienced greater subjective cognitive difficulties and symptoms of depression and anxiety than those who maintained or increased their physical activity levels.

301 participants (73% non-Hispanic whites) completed an online survey in either English or Spanish between May and October 2020 and 3 months later. The Everyday Cognition Scale was used to measure subjective cognitive decline, the CES-D-R-10 scale to measure depressive symptoms, and the GAD-7 scale to measure anxiety symptoms. Changes in physical activity were measured with the question “Since the coronavirus disease pandemic began, what has changed for you or your family in regard to physical activity or exercise levels?” with options “less physical activity,” “increase in physical activity,” or “same activity level.” Income was self-reported as high, middle, or low. Analyses of chi-squared tests were used to examine differences in physical activity maintenance by age, income level, sex, and employment status.

Most individuals (60%) reported having decreased their physical activity levels during the pandemic, at baseline and 3-month followup. There were differences in physical activity levels based on income and age: participants with a high income reported engaging in more physical activity than those with low income (X^2=4.78, p =.029). At the 3-month follow-up, middle-income participants reported being less active than the high-income earners (X^2=8.92, p=.003), and younger participants (55-65 years, approximately) reported being less active than older participants (X^2=5.28, p =.022). Those who reported an increase in their physical activity levels had fewer cognitive concerns compared to those who were less active at baseline, but this difference was not seen in the 3-month follow-up. Participants of all ages who reported having maintained or increased their physical activity levels had fewer depressive symptoms than those who were less active (p < 0.0001). Those who reported maintaining their physical activity levels exhibited fewer anxiety symptoms than those who were less active (p < 0.01).

Older adults reported changes in physical activity levels during the pandemic and some of these changes varied by sociodemographic factors. Further, maintaining physical activity levels was associated with lower symptoms of depression, anxiety, and cognitive concerns. Encouraging individuals and providing resources for increasing physical activity may be an effective way to mitigate some of the pandemic’s adverse effects on psychological wellbeing and may potentially help reduce the risk for cognitive decline. Alternately, it is possible that improving emotional distress could lead to an increase in physical activity levels and cognitive health.

Fear of falling is an anxiety-related phenomenon that is associated with increased risk of morbidity and mortality in older adults. Furthermore, a growing body of research has established the relationship between fear of falling and decreased cognitive functioning within various populations (i.e., older adult, multiple sclerosis, stroke survivors). Yet there is little information on the relationship between fear of falling and cognition outside of a geriatric context, with no publications investigating this relationship within informal caregivers. It is important to understand this relationship within caregiver populations because fear of falling may negatively impact caregivers’ ability to take care of themselves and their care recipients. The present study examines the relationship between fear of falling and cognitive function in informal caregivers.

Fifty informal caregivers (86% female; 58% White; 10% Hispanic or Latino; 82% married; 53% with at least a bachelor’s degree; mean age = 57.76 ± 16.60 years) were assessed at the VA Palo Alto Health Care System in Palo Alto, CA. Fear of falling was measured via the Short Falls Efficacy Scale. Areas of cognitive functioning included verbal attention (Rey Auditory Verbal Learning Task [RAVLT] Trial 1), learning and memory (RAVLT Trials 1-5), delayed memory (RAVLT Delayed Recall), visual attention (Stroop Color, Stroop Word), and executive function (Stroop Color Word). Analyses included linear regressions with age as a covariate in all models.

Analyses revealed that fear of falling was significantly associated with decreased verbal attention (RAVLT Trial 1: ß=-0.34, p = 0.02, t = -2.35, CI = [-0.659, -0.051]) and with decreased executive functioning (Stroop Color Word: ß = -0.35, p < 0.001, t = -3.10, CI = [-4.097, -0.874]). Fear of falling was not significantly associated with learning and memory or visual attention.

Fear of falling negatively impacts verbal attention and executive functioning, regardless of age. To our knowledge, this is the first study to examine the relationship between fear of falling and cognition outside of a geriatric population and within a caregiver sample. Findings suggest a need for additional assessment, research, and treatment of fear of falling within informal caregivers. Caregivers may need to be assessed for anxiety-related symptoms such as fear of falling on a more regular basis. A caregiver experiencing fear of falling, as well as difficulties with attention and executive functioning, can result in increased risk of functional and cognitive decline for both the caregiver and their care recipient. It is integral that future research investigates this relationship longitudinally to identify if the negative impact of fear of falling on cognition is reversible.

Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer’s disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs.

62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD.

Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD.

Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting.

As the US population ages, the prevalence of Alzheimer’s disease and related dementias (AD/RD) is on the rise. This is especially true in rural America, where mortality rates due to AD/RD are rising faster than in metropolitan areas. To date, however, people living in rural communities are severely underrepresented in aging research. The Nevada Exploratory Alzheimer’s Disease Research Center (NVeADRC) seeks to address this gap. Here, we present preliminary cognitive data from our rural-dwelling cohort, as well as relevant demographic and clinical characteristics.

Individuals with normal cognition (NC), mild cognitive impairment (MCI), and dementia due to Alzheimer’s disease (AD) living in rural communities, defined as a rural-urban commuting area (RUCA) code of 4 or higher, were enrolled through either clinic or community outreach. Eligibility for the observational cohort required: age >55 years, primarily English-speaking, primary residence in a rural community, and availability of a study partner. Measures included the Uniform Data Set (v3), blood-based biomarkers, structural brain MRI, and portions of the PhenX Social Determinants of Health toolkit. Participants are seen at baseline and followed annually, with interim remote visits every 6 months. A multidisciplinary consensus diagnosis is rendered after each visit. Where feasible, a harmonized urban cohort followed by the Nevada Center for Neurodegeneration and Translational Neuroscience (CNTN) was used for comparison.

Fifty-six rural-dwelling (age=70.4±7.1 years; edu=15.2±2.6 years; 61% female) and 148 urban-dwelling (age=72.9±6.8 years; edu=15.8±2.7 years; 46% female) older adults were included; age significantly differed between cohorts but education did not. The rural cohort was 46% NC (MoCA=26.8±2.3; CDRsob=0.3±0.6), 32% MCI (MoCA=22.8±3.1; CDRsob=1.2±1.0), and 22% AD (MoCA=16.9±5.5; CDRsob=5.2±3.0). The urban cohort was 39% NC (MoCA=26.4±2.6; CDRsob=0.3±0.8), 44% MCI (MoCA=22.3±3.1; CDRsob=2.0±1.5) and 17% AD (MoCA=18.6±3.9; CDRsob=4.7±2.3). Rural communities were significantly more disadvantaged, as measured by the Area Deprivation Index (ADI), than urban communities (rural ADI=6.3±2.6; urban ADI=3.4±2.3; p<.001). Fifty-percent of the rural cohort lives in a moderate to severely disadvantaged neighborhood (ADI Decile>7) compared to 12% of the urban cohort, and 11% of individuals in the rural cohort reported living more than 30 miles from the nearest medical facility. Across the combined cohort, education was significantly correlated with ADI deciles (r=-.30, p<.001), with people in the areas of highest disadvantage having the lowest education. Verbal memory was also inversely associated with ADI. There were no differences in clinical diagnosis as a function of ADI rank.

Living in a rural community conveys a multifaceted array of risks and benefits, some of which differ from urban settings. The literature to date suggests that older adults living in rural communities are at significantly increased risk for morbidity and mortality due to AD/RD, though it is unclear why. Preliminary data from the NVeADRC show that increasing levels of neighborhood disadvantage were associated with lower levels of education and worse verbal memory in this convenience sample. The combined effect of low education and increased disadvantage account for some of the urban-rural differences in mortality that have been reported, though additional research on representative samples in this underrepresented population is critical.

Differences in adaptive functioning present early in development for many children with monogenic (Down Syndrome, Fragile X) and neurodevelopmental disorders. At this time, it is unclear whether children with ACC present with early adaptive delays, or if difficulties emerge later as functional tasks become more complex. While potential delays in motor development are frequently reported, other domains such as communication, social and daily living skills are rarely described. We used a prospective, longitudinal design to examine adaptive behavior from 6-24 months in children with ACC and compared their trajectories to those with monogenic and neurodevelopmental conditions.

Our sample included children with primary ACC (n= 27-47 depending on time point) whose caregivers completed the Vineland Adaptive Behavior Scales-Interview 3rd Edition, via phone at 6, 12, 18 and 24 months. Comparison samples (using the Vineland-2) included children with Down Syndrome (DS; n = 15-56), Fragile X (FX; n = 15-20), children at high familial likelihood for autism (HL-; n=192-280), and low likelihood (LL; no family history of autism and no developmental/behavioral diagnosis; n = 111196). A subset of the HL children received an autism diagnosis (HL+; n = 48-74). The DS group did not have an 18-month Vineland.

A series of linear mixed model analyses (using maximum likelihood) for repeated measures was used to compare groups on three Vineland domains at 6, 12, 18 and 24 month timepoints). All fixed factors (diagnostic group, timepoint, and group X timepoint interaction) accounted for significant variance on all Vineland domains (p < .001). Post hoc comparisons with Bonferroni-correction examined ACC Vineland scores compared to the other diagnostic groups at each timepoint. At 6 months, parent-ratings indicated the ACC group had significantly weaker skills than the LL group in Communication and Motor domains. At 12, 18 and 24 months, ratings revealed weaker Communication, Daily Living and Motor skills in the ACC group compared to both the LL and HL- groups. Compared to the other clinical groups, the ACC group had stronger Socialization and Motor skills than Fragile X at 6 months, and at 24 months had stronger Communication and Socialization skills than both the DS and FX groups, as well as stronger Socialization than the HL+ group.

Compared to children with low likelihood of ASD, children with primary ACC reportedly have weaker Communication and Motor skills from 6 to 24 months, with weakness in Daily Living Skills appearing at 12 months and all differences increase with age. Compared to Fragile X, the ACC exhibited relative strengths in socialization and motor skills starting at 6 months. By 24 months, the ACC group was outperforming the monogenic groups on Socialization and Communication. In general, the ACC scores were consistent with the HL+ sample, except the ACC group had stronger Social skills at 18 and 24 months. The results clearly inform the need for early intervention in the domains of motor and language skills. Additionally, as we know that children with ACC are at increased risk for social difficulties, research is needed both using more fine-grained social-communication tools, and following children from infancy through middle childhood.

Agenesis of the Corpus Callosum (ACC), a congenital disorder in which the corpus callosum partially or completely fails to develop properly, occurs in ∼1 in 4,000 live births. ACC has been identified as a major risk factor for receiving an Autism Spectrum Disorder (ASD) diagnosis (∼10% diagnosis rate, as compared to 2.3% in the general population), but little is currently known about behavioral and social development during infancy and early childhood in this disorder. In this study we aim to 1) characterize the manifestation of autistic features in 24-month-old children (a common age for early diagnosis of ASD) with ACC and a convenience sample of age matched comparison children from the community, and 2) determine if parent reports of autistic features during the first year of life are associated with reciprocal social behavior and autistic traits at 24-months of age in children with ACC.

Parents of infants who had received a diagnosis of ACC completed the Parent Rating of Communication, Emotion, and Social Skills (PROCESS) for their child at 6, 12, and 24-months of age, and the video-referenced rating of reciprocal social behavior (vrRSB) at 24-months of age. Comparison data were obtained from a convenience community sample in Minnesota. Aim 1). The distributions of PROCESS total scores at 24-months were compared between the ACC group (n=43) and control group (n=1058) via a 2-tailed t-test. Likewise, distributions of reciprocal social behavior (RSB) scores at 24 months were compared between ACC (n=72) and controls (n=1438) via a 2-tailed t-test. Aim 2). A partial Pearson Correlation was conducted between ACC participants’ 6-month PROCESS scores and 24-month RSB (n=18) scores, as well as between their 12-month PROCESS and 24-month vrRSB (n=37) scores, controlling for child sex.

Aim 1). At 24 months of age, children with ACC are reported to have significantly higher PROCESS scores (t = 3.73, df = 42.67, p < .001), and RSB (t = 4.89, df = 88.38, p < .001) scores than comparison toddlers, indicating an elevated presentation of behaviors associated with autistic features. Aim 2). No correlation was found between participants’ 6-month PROCESS and 24-month RSB scores (r(16) = .39, p = .12). A relatively strong correlation (r(35) = .60, p < .001) was found between participants’ 12-month PROCESS and 24-month RSB scores.

As early as two years of age, children with ACC display a heightened presentation of autistic features compared to typically developing controls. Additionally, reports of social behaviors related to ASD at 24-months are correlated with reports of autistic features at 12-months of age. This evidence indicates that children with ACC who are at a higher likelihood for being diagnosed with ASD may be identified as early as 12-months old. Formulating and leveraging an early identification methodology is imperative for this population with an already elevated risk for ASD, as providing early interventions leads to improved outcomes later in life.

Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.

Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).

Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.

These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.

It is unclear how agenesis of the corpus callosum (ACC), a congenital brain malformation defined by complete or partial absence of the corpus callosum, impacts language development. fMRI studies of middle childhood suggest that the corpus callosum plays a role in the interhemispheric language network (Bartha-Doering et al., 2020), and that reduced interhemispheric functional connectivity is correlated with worse language abilities in children with ACC (Bartha-Doering et al., 2021). Additionally, accumulating evidence suggests structural abnormalities of the corpus callosum play a role in neurodevelopmental disorders. While children who go on to receive an autism spectrum disorder (ASD) diagnosis may show early signs of altered word and gesture acquisition (Iverson et al., 2018), the same is not known about ACC. This study examined language development during the second year of life in children with ACC in comparison to neurotypical control participants, as well as other children at elevated risk of ASD.

The MacArthur-Bates Communicative Development Inventories (MCDI): Words and Gestures scales were administered to parents of 74 children with isolated ACC at 12, 18 and 24 months of age. Children whose first language was not English and children who were bilingual were excluded. Comparison groups consisted of individuals with a low familial likelihood of ASD (LL- n=140) and individuals with high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=68, HL- n=256).

Compared to LL controls, the ACC group produced fewer words at 18 and 24 months of age, and demonstrated fewer words understood at all three timepoints. Similarly, compared to the HL- group, the ACC group demonstrated fewer words produced and understood at 18 months of age, and fewer words produced at 24 months of age. The ACC and HL+ groups did not differ in words produced or words understood at any timepoint.

Overall, infants with ACC demonstrated delayed vocabulary expansion from 12 to 24 months of age. These findings illustrate the role of callosal connectivity in the development of language across the first 2 years of life, and highlight the need for support and interventions that target vocabulary production and comprehension.