Persons at risk for autosomal dominant neurodegenerative diseases provide the opportunity to efficiently test preventive interventions. Only a minority of such persons, however, choose to undergo revealing genetic testing, presenting a challenge to enrollment. Thirty-four preclinical Latinos (n = 26) and non-Latinos at risk for familial Alzheimer's disease (FAD) unaware of their genetic status were administered a questionnaire exploring their interest in undergoing revealing genetic testing at baseline and in the context of eligibility for four prevention trials of increasing invasiveness. Forty-four percent of subjects expressed a baseline interest in undergoing revealing testing which increased to 85% in order to be eligible for a study of an oral drug "felt to be very safe." If there were a 50% chance of receiving placebo, this number dropped to 62% (p = 0.02). Among those not interested in a study involving a 50% chance of receiving placebo, a range of 5% to 40% chance of receiving placebo was given as acceptable. For more invasive studies, living in the United States (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggest that clinical trial designs in which persons must confront their genetic status prior to enrollment are feasible. Study designs to minimize the likelihood of being placed on placebo or provide the eventual administration of the drug through open-label extensions should be considered.

Alzheimer’s disease (AD) is characterized by the presence of neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD). BPSD have been associated with the APOE_ε4 allele, which is also the major genetic AD risk factor. Although the involvement of some circadian genes and orexin receptors in sleep and behavioral disorders has been studied in some psychiatric pathologies, including AD, there are no studies considering gene–gene interactions. The associations of one variant in PER2, two in PER3, two in OX2R and two in APOE were evaluated in 31 AD patients and 31 cognitively healthy subjects. Genotyping was performed using real-time PCR and capillary electrophoresis from blood samples. The allelic-genotypic frequencies of variants were calculated for the sample study. We explored associations between allelic variants with BPSD in AD patients based on the NPI, PHQ-9 and sleeping disorders questionnaires. Our results showed that the APOE_ε4 allele is an AD risk variant (p = 0.03). The remaining genetic variants did not reveal significant differences between patients and controls. The PER3_rs228697 variant showed a nine-fold increased risk for circadian rhythm sleep–wake disorders in Mexican AD patients, and our gene–gene interaction analysis identified a novel interaction between PERIOD and APOE gene variants. These findings need to be further confirmed in larger samples.

Traumatic brain injury (TBI) is associated with depression, anxiety, and even suicidality in individuals with TBI and in caregivers. Moreover, emotional functioning in individuals with TBI is linked with caregiver functioning. However, no known studies to date have examined linkages in suicidal ideation in individuals with TBI and family caregivers. This is especially important in Latin America, where TBI rates are high, and where cultural norms influence family caregiving. This study examined associations among self-reported suicidal ideation in individuals with TBI and their primary caregivers over time in Mexico and Colombia. A total of 109 individuals and their primary caregivers completed measures during hospitalization for TBI and at two- and four-months post-hospitalization. The primary outcome was item 9 from the Spanish version of the Patient Health Questionnaire-9, assessing for thoughts of death or suicide in the previous two weeks. Patients and caregivers reported high levels of suicidal ideation (18.3-22.4% and 12.4-15.7%, respectively) at each time point, and suicidal ideation at one time point strongly predicted ideation at the next. When patients endorsed suicidal ideation in the hospital, their caregivers tended to endorse suicidal ideation two months later; although unaccounted for variables could be driving these relationships, they may also provide possible evidence of causal preponderance between patient and caregiver suicidal ideation post-TBI. Clinicians and rehabilitation specialists can use these findings to inform suicide risk assessment by expanding these practices to caregivers of patients who endorsed suicidal ideation. Interventions after TBI should incorporate caregivers given this study showed significant interdependence of suicidality between patients and caregivers.

The world is aging and experiencing loneliness. Functional impairment in instrumental activities of daily living (IADL) in older people (OP) with mild neurocognitive disorder (MNCD) predicts loneliness. After the pandemic, there was an increase in perceived loneliness. We explored the association between loneliness, depression, deficits in IADL, and cognitive symptoms among OP. From February to December 2023, using a cross-sectional design, we interviewed probable cases with mild cognitive impairment and caregivers in two public facilities. We administered the UCLA Loneliness Scale v3, Lawton IADL Scale, Mini-Mental State Examination (MMSE), and Yesavage’s Geriatric Depression Scale. Samples were matched: 85 per group, 82.4% were women, married (52.95%), and mean age of 69.17 (±6.93) years. In our study, 30% displayed moderate to high levels of perceived loneliness. Multivariate analysis showed loneliness was associated with depression, low levels of IADL, and older age, but not with cognitive symptoms, which explained 22% of the total variance (F 165) = 16.99, (p < 0.001). Targeting symptoms and behaviors that could be modified (i.e., depression and functionality) can improve feelings of perceived loneliness and have an impact on morbidity and mortality with which it is associated.

Mild Behavioral Impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we described the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. 246 participants were included, 13.0% had subjective cognitive decline and 30.9% mild cognitive impairment. 37% (91/246) of participants from all the cognitive spectrum met the MBI criteria; among this group, being carrier of APOEε4 was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7-15.89). The first three components of PCA explained 68.0% of the variance of the data set, including MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a relevant marker for cognitive decline in non-demented MM elderly people.