UNASSIGNED: Alzheimer\'s disease (AD) is related to one or more chronic illnesses, which may develop cognitive decline and dementia. Cognitive impairment is increasing, and public health officials must address risk factors for AD to improve the health of rural West Texas communities.
UNASSIGNED: The purpose of this study was to explore the sociodemographic and chronic disease risk factors related to cognitive impairment among elderly adults living in Cochran, Parmer, and Bailey counties in rural West Texas.
UNASSIGNED: Statistical methods such as Pearson\'s chi-squared, proportion tests, univariate binary logistic regression, and a multivariable logistic regression were utilized to analyze data. SPSS software was used to detect the significant relationship between cognitive impairment and risk factors.
UNASSIGNED: Summary statistics were obtained for sociodemographic and chronic diseases by using cross-tabulation analysis and comparing the county respondents with proportion tests. A univariate binary logistic regression method was utilized and found that age group 60-69, anxiety, depression, diabetes, hypertension, and cardiovascular disease were significantly associated with cognitive impairment. Using a multivariable logistic regression approach, it was found that Bailey County (age group 60-69) had a higher likelihood (p = 0.002) of cognitive impairment than Parmer (p = 0.067) and Cochran counties (p = 0.064). The risk of females (p = 0.033) in Parmer County was 78.3% lower compared to males in developing AD.
UNASSIGNED: Identifying significant risk factors for cognitive impairment are important in addressing issues of geographic variations and integrating such factors may guide relevant policy interventions to reduce cognitive impairment incidence in rural communities within West Texas.

UNASSIGNED: Identifying high-risk individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer\'s disease (AD) is crucial for early intervention.
UNASSIGNED: This study aimed to develop and validate a novel clinical score for personalized estimation of MCI-to-AD conversion.
UNASSIGNED: The data from the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) study were analyzed. Two-thirds of the MCI patients were randomly assigned to a training cohort (n = 478), and the remaining one-third formed the validation cohort (n = 239). Multivariable logistic regression was performed to identify factors associated with MCI-to-AD progression within 4 years. A prediction score was developed based on the regression coefficients derived from the logistic model and tested in the validation cohort.
UNASSIGNED: A lipidomics-signature was obtained that showed a significant association with disease progression. The MCI conversion scoring system (ranged from 0 to 14 points), consisting of the lipidomics-signature and five other significant variables (Apolipoprotein ɛ4, Rey Auditory Verbal Learning Test immediate and delayed recall, Alzheimer\'s Disease Assessment Scale delayed recall test, Functional Activities Questionnaire, and cortical thickness of the AD signature), was constructed. Higher conversion scores were associated with a higher proportion of patients converting to AD. The scoring system demonstrated good discrimination and calibration in both the training cohort (AUC = 0.879, p of Hosmer-Lemeshow test = 0.597) and the validation cohort (AUC = 0.915, p of Hosmer-Lemeshow test = 0.991). The risk classification achieved excellent sensitivity (0.84) and specificity (0.75).
UNASSIGNED: The MCI-to-AD conversion score is a reliable tool for predicting the risk of disease progression in individuals with MCI.

UNASSIGNED: The present study examined the cognitive reserve (CR) theory at late stages of Alzheimer\'s disease (AD). The objective is to replicate previous studies and examine the complex role of education and family size as indicators of CR.
UNASSIGNED: This is a retrospective study included 642 patients diagnosed with AD after age 65, categorized into low education (LE, ≤ 8 years, n = 141) and medium-high education (MHE, ≥ 9 years, n = 442) groups. Participants were followed up longitudinally using the Mini Mental State Examination.
UNASSIGNED: Higher education in the MHE group, but not in the LE group, correlated with delayed diagnosis. In both groups, higher education correlated with accelerated cognitive decline. In the MHE group, country of origin was associated with cognitive decline, while in the LE group, it was linked to family size.
UNASSIGNED: This study shows that in patients with MHE but not in LE, higher education resulted in delayed diagnosis. Conversely, in cases of LE, this measure may not fully reflect CR and abilities. Additionally, higher education was associated with faster deterioration, a finding that has not been replicated often in the literature. The study illustrates the complex impact of CR proxies on age of diagnosis and cognitive decline.

BACKGROUND: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted.
METHODS: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer\'s Disease (AD) Assessment Scale\'s (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS.
RESULTS: Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94-5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19-0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05-1.39) and 0.63 units (95% CI 0.19-1.08) more severe NPS. NPS number (MMSE mean difference - 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26-2.56) and severity (MMSE - 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57-1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect - 0.08, 95% CI -0.22 to -0.002).
CONCLUSIONS: This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA.

Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar n = 71, non-lobar n = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); P = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; P = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; P < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; P = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; P = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer\'s disease neuropathologic change.

Background and Objectives: Traditional methods of fidelity monitoring are not possible in pragmatic trials in real-world clinical settings. We describe our approach to monitoring and reinforcing the fidelity to ACP conversations for a hard-to-reach subpopulation by using standardized patients in a pragmatic trial. Research Design and Methods: We developed standardized patient scenarios grounded in the Respecting Choices First Steps™ Advance Care Planning curriculum to provide an opportunity to reinforce and assess ACP facilitator competency. Scenarios represented one-on-one encounters. The first case was a standardized patient with cognitive impairment and the second case involved a standardized patient with dementia and their care partner. A previously validated fidelity checklist was used to score skills and behaviors observed during simulations including encounter set-up, ACP topics, and general communication. Simulations involved voice teleconferencing to align primary modality of ACP in the pragmatic trial. Results: Six facilitators completed two standardized patient cases each. Overall fidelity scores were moderately high (78.8% ± 11.7; 63.4 - 95.6) for the case with cognitive impairment and for the case with the patient with dementia and care partner (76.2% ± 13.0; 54.4 - 91.5). Discussion and Implications: Simulation using standardized patients supported fidelity monitoring and provided coachable feedback to support facilitator competency. Our study can help inform future research and training related to advance care planning in older adults living with Alzheimer\'s disease and related disorders.

BACKGROUND: Latinos are more likely than non-Latino Whites to develop dementia and be prescribed antipsychotics for dementia-related behavioral symptoms. Antipsychotics have significant risks yet are often overprescribed. Our understanding of how Latino caregivers of Latino older adults living with dementia perceive and address behavioral issues is limited, impeding our ability to address the root causes of antipsychotic overprescribing.
METHODS: We interviewed Latino older adults\' caregivers and community-based organization workers serving older adults with cognitive impairment (key informants), focusing on the management of behavioral symptoms and experiences with health services.
RESULTS: We interviewed 8 caregivers and 2 key informants. Caregivers were the spouses, children, or grandchildren of the older adult living with cognitive impairment; their ages ranged from 30 to 95. We identified three categories of how caregivers learned about, managed, and coped with behavioral symptoms: caregivers often faced shortcomings with dementia care in the medical system, receiving limited guidance and support; caregivers found community organizations and senior day centers to be lifelines, as they received relevant, timely advice and support, caregivers often devised their own creative strategies to manage behavioral symptoms.
CONCLUSIONS: In-depth interviews suggest that the healthcare system is failing to provide support for behavioral symptoms from dementia; caregivers of Latino older adults rely on community organizations instead.

BACKGROUND: The associations between one-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B6, and vitamin B12) and Alzheimer\'s disease (AD) remains inconclusive.
OBJECTIVE: This study aims to investigate the association of dietary OCM nutrients with the subsequent risk of AD, and further assessed whether participants with a high genetic risk for AD might benefit from dietary OCM nutrients.
METHODS: We analyzed data from 192,214 participants who completed at least one 24-hour dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson\'s The Composition of Food and USDA\'s Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations.
RESULTS: Over a median follow-up of 13.35 years, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared to those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had a reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% CI for methionine, folate, vitamin B6, and vitamin B12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B12 intake were associated with a 70% (HR = 0.30, 95% CI: 0.10, 0.86) and 71% (HR = 0.29, 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had a >75% reduced AD risk compared to high-risk, low-intake participants.
CONCLUSIONS: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with a reduced risk of AD. Participants with a high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake.

UNASSIGNED: Intranasal insulin (INI) is being explored as a treatment for Alzheimer\'s disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes.
UNASSIGNED: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system.
UNASSIGNED: To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans.
UNASSIGNED: We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq.
UNASSIGNED: The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans.

UNASSIGNED: The Clock Drawing Test (CDT) is used to screen for Alzheimer\'s disease and other dementia disorders. Normative scores on the version from the Montreal Cognitive Assessment (MoCA) do not exist in the Nordic countries.
UNASSIGNED: To examine the normative scores of the CDT among adults aged 70 years and older.
UNASSIGNED: We included 4,023 cognitively healthy persons aged 70-97 years from a population survey in Norway. They were examined with the CDT, which has a total score between zero and three. A multiple multinominal regression model was applied with a CDT score as the dependent categorical variable and estimated the probabilities of scoring a particular score, stratified by age, sex, and education. These probabilities correspond to an expected proportion of the normative population scoring at, or below a given percentile.
UNASSIGNED: None scored zero, 2.1% scored one, 14.9% scored two, and 83% scored three. Higher age, female sex and fewer years of schooling were associated with poorer performance. Scores of zero and one deviated from the normative score regardless of age, sex and education. A score of two was within the norm for a female older than 81 and a male older than 85.
UNASSIGNED: The majority (83%) of people 70 years and older had a score of three on the CDT. Lower age, male sex, and higher education were associated with a better performance. Scores of zero and one were below the normative score. Except for the very old, a score of two was also well below the normative score.