History of traumatic brain injury (TBI) is associated with increased risk of dementia, but few studies have evaluated whether TBI history alters the course of neurocognitive decline, and existing literature on this topic is limited to short follow-up and smaller samples. The primary aim of this study was to evaluate whether a history of TBI (TBI+) influences neurocognitive decline later-in-life among older adults with or without cognitive impairment [i.e., normally aging, Mild Cognitive Impairment (MCI), or dementia].

Participants included individuals from the National Alzheimer’s Coordinating Center (NACC) who were at least 50 years old and with 3 to 6 visits (M number of visits = 4.43). Participants with any self-reported history of TBI (n = 1,467) were matched 1:1 to individuals with no reported history of TBI (TBI-) from a sample of approximately 45,000 participants using case-control matching based on age (+/- 2 years), sex, education, race, ethnicity, cognitive diagnosis [cognitively normal (CN), MCI, or all-cause dementia], etiology of cognitive impairment, functional decline (Clinical Dementia Rating Scale, CDR), number of Apolipoprotein E4 (APOE ε4) alleles, and number of annual visits (3 to 6). Mixed linear models were used to assess longitudinal neuropsychological test composites (using NACC normative data) of executive functioning/attention/speed (EFAS), language, and memory in TBI+ and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined.

Following matching procedures, TBI+ (n=1467) and TBI- (n=1467) groups were nearly identical in age (TBI+ M = 71.59, SD = 8.49; TBI- M = 71.63, SD = 8.44), education (TBI+ M = 16.12, SD = 2.59; TBI- M = 16.10, SD = 2.52), sex (both 55% male), race (both 90% White), ethnicity (both 98% non-Hispanic), APOE ε4 alleles (both 0 = 62%, 1 = 33%, 2 = 5%), baseline cognitive diagnoses (both CN = 60%, MCI = 18%, dementia = 12%), and global CDR (TBI+ M = 0.30, SD = 0.38, TBI- M = 0.30, SD = 0.38). At baseline, groups had similar Z-scores of in EFAS (TBI+ Mefas = -0.02, SD = 1.21; TBI- Mefas = -0.04, SD = 1.27), language (TBI+ MLanguage = -0.48, SD = 0.98; TBI- MLanguage = -0.55, SD = 1.05), and memory (TBI+ MMemory = -0.45, SD = 1.28; TBI- MMemory = -0.45, SD =1.28). The course of change in neuropsychological functioning worsened longitudinally, but did not differ between TBI groups (p’s > .110). There were no significant interactions between TBI history and age, sex, education, race/ethnicity, number of APOE ε4 status, or cognitive diagnosis (all p’s > .027).

In this matched case-control design, our findings suggest that a history of TBI, regardless of demographic factors, APOE ε4 status, and cognitive diagnosis, does not significantly alter the course of neurocognitive functioning later-in-life in older adults with and without cognitive impairment. Future clinicopathological longitudinal studies with well characterized TBI histories and the associated clinical course are needed to help clarify the mechanism by which TBI may increase dementia risk for some individuals, without affecting course of decline.

Additional research is needed to better understand the relationship between early tau accumulation and cognitive decline in cognitively healthy (CH) older adults. The tau PET tracer 18F-MK-6240 has shown favorable imaging characteristics and is an ideal candidate to identify early tau accumulation in CH older adults. In the present study, we evaluated the associations between in vivo tau levels and retrospective 5-year cognitive change.

Using 18F-MK-6240 PET, we evaluated tau accumulation in 41 CH participants from Cognitive Reserve (CR) and Reference Ability Neural Network (RANN) studies. We investigated the relationships between regional PET signal and retrospective cognitive change, focusing in three cognitive domains well-established to change with aging: episodic memory, speed processing and reasoning. Latent change score analysis was applied to generate latent variables estimating the change in these domains from baseline to follow-up. Regarding tau data, we created meta-ROIs based on 16 AD-vulnerable subregions selected a priori. The tau SUVR of the subregions were averaged to create four meta-ROIs: 1) Total-AD ROI comprising all 16 areas; 2) Medial Temporal Lobe-ROI (MTL-ROI), 3) Lateral Temporal Lobe-ROI (LTL-ROI) and Cingulate/Parietal Lobe (C/P-ROI). The associations between regional tau levels and retrospective cognitive change over 5-years were investigated through regression models adjusted by age, sex, education, and baseline cognitive performance.

The mean age of the sample was 67.5 years (SD=5.8, range 55 to 77 years), 53.8% were male, 63.4% White, 26.1% Black, and 7.3% Latinx. Overall, the sample was highly educated (16.20 ± 2.26) and presented high IQ scores (118.97 ± 7,76) based on American National Adult Reading Test. All participants were CH and showed cognitive decline over 5 years in all cognitive domains analyzed. Most participants were classified as Braak stage 0 (82.9%), some as Braak stage 1 (14.6%) and one participant as Braak stage 2 (2.4%). The regression models showed that higher [18F]MK-6240 SUVR was associated with steeper decline in memory and speed in the Total-AD meta-ROI (memory: p = .03; speed: p = .04), and in the regional ROIs, such as LCL (memory: p = .03; speed: p = .04), C/P (memory: p = .02, speed: p = .05) and MTL (memory: p = .05, speed: p = .02), with large effect sizes (f2) (>.40) for memory and medium effect sizes for speed (.20-.25). There were no associations between [18F]MK-6240 SUVR and reasoning change.

Our finding reinforces the notion that pathological tau in areas of early accumulation influence changes in cognitive domains known to be affected in AD even in cognitively normal individuals. The novel contribution of this work is the relevance of tau accumulation beyond episodic memory, as we observed its association with speed proceeding decline. The fact reasoning decline is commonly observed in normal aging, but here not associated with tau suggest the specificity of the tau-cognition associations. Our results should be considered with caution due to the modest sample size.

Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

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.