TICS-M scores in an oldest-old normative cohort identified by computable phenotype.

Objective: To (1) examine the distribution of Telephone Interview for Cognitive Status modified (TICS-m) scores in oldest-old individuals (age 85 and above) identified as cognitively healthy by a previously validated electronic health records-based computable phenotype (CP) and (2) to compare different cutoff scores for cognitive impairment in this population. Method: CP identified 24,024 persons, 470 were contacted and 252 consented and completed the assessment. Associations of TICS-m score with age, sex, and educational categories (<10 years, 11-15 years, and >16 years) were examined. The number of participants perceived as impaired was studied with commonly used cutoff scores (27-31). Results: TICS-m score ranged from 18 to 44 with a mean of 32.6 (SD = 4.7) in older adults aged 85-99 years old. A linear regression model including (range-restricted) age, education, and sex, showed beta estimates comparable to previous findings. Different cutoff scores (27 to 31) generated slightly lower MCI and dementia prevalence rates of participants meeting the criteria for the impairments than studies of younger elderly using traditional recruitment methods. Conclusions: The use of validated computable phenotype to identify a normative cohort generated a normative distribution for the TICS-m consistent with prior findings from more effortful approaches to cohort identification and established expected TICS-m performance in the oldest-old population.

Multimodal cognitive and behavioral interventions for patients with MCI: a systematic review and meta-analysis on cognition and mood.

Background: Research has increasingly suggested a benefit to combining multiple cognitive or behavioral strategies in a single treatment program for cognitively impaired older adults. Therefore, this systematic review and meta-analysis aimed to summarize results on the effects of multimodal cognitive and behavioral interventions versus control conditions on changes in cognition and mood in patients with mild cognitive impairment (pwMCI). Methods: The review followed a general PRISMA guideline for systematic literature review with a format consisting of participants, interventions, comparators, and outcomes (PICO). Multilevel meta-analyses of aggregated efficacy were performed to assess the pooled effect sizes for cognitive and mood outcomes. Risk-of-bias, heterogeneity across studies, and publication bias were assessed for each outcome. Results: After primary and reference searches, 18 studies with low or some concerns of risk of bias were included. Low heterogeneity was found for mood and cognition. Funnel plots did not indicate publication bias. All the studies assessed changes in cognition (n = 1,555) while seven studies with mood outcomes (n = 343) were included. Multilevel meta-analyses demonstrated moderate effect (Hedge's g = 0.44, 95% CI = [0.21-0.67]) in cognitive outcomes and large effect in mood (g = 0.65, 95% CI = [0.37-0.93]). Subdomain analyses found low-moderate effects in global cognition, verbal and non-verbal memory, executive function, visuospatial abilities, and semantic fluency (0.20 < g < 0.50). Conclusion: These findings showed comparable to larger effects of multimodal cognitive and behavioral interventions on cognition than pharmacological treatment. Future studies should focus on the longitudinal effects of multimodal interventions in delaying dementia.Systematic review registration: PROSEPRO, CRD42022349297.

Hippocampal Subfields in Mild Cognitive Impairment: Associations with Objective and Informant-Report of Memory Function.

BACKGROUND: Evidence suggests that select hippocampal subfields are implicated in the initial stages of Alzheimer's disease (AD) and are selectively involved in objective memory. Less is known whether subfields are associated with informant-reported memory difficulties of individuals with a diagnosis of mild cognitive impairment (MCI). METHOD: Data from 56 participants with a diagnosis of amnestic MCI were included in the present study. To test whether FreeSurfer derived hippocampal subfields (CA1-4, subiculum, presubiculum, and dentate gyrus) were associated with objective (learning and delayed recall) and informant-reports of memory difficulties, we used multiple linear regression analysis. Subfields were adjusted for total intracranial volume, and age, sex, and years of education were included as covariates in all models. RESULTS: Larger presubiculum, subiculum, and CA4/dentate gyrus volumes were associated with higher delayed recall scores, and larger subiculum and CA4/dentate gyrus volumes were associated with fewer informant-reports of memory difficulties. There were no statistically significant associations between subfields and learning scores. DISCUSSION: Findings from the present study support the idea that difficulties with memory-dependent everyday tasks in older adults with MCI may signal a neurodegenerative process while increasing understanding of subfields correlates of these memory-specific functional difficulties. Continued investigations into identifying patterns of subfield atrophy in AD may aid early identification of those at higher risk of dementia conversion while advancing precision medicine.

Critical Review of the Alzheimer's Disease Non-Transgenic Models: Can They Contribute to Disease Treatment?

Alzheimer's disease (AD) is a growing neurodegenerative disease without effective treatments or therapies. Despite the use of different approaches and an extensive variety of genetic amyloid based models, therapeutic strategies remain elusive. AD is characterized by three main pathological hallmarks that include amyloid-ß plaques, neurofibrillary tangles, and neuroinflammatory processes; however, many other pathological mechanisms have been described in the literature. Nonetheless, the study of the disease and the screening of potential therapies is heavily weighted toward the study of amyloid-ß transgenic models. Non-transgenic models may aid in the study of complex pathological states and provide a suitable complementary alternative to evaluating therapeutic biomedical and intervention strategies. In this review, we evaluate the literature on non-transgenic alternatives, focusing on the use of these models for testing therapeutic strategies, and assess their contribution to understanding AD. This review aims to underscore the need for a shift in preclinical research on intervention strategies for AD from amyloid-based to alternative, complementary non-amyloid approaches.

Apolipoprotein ɛ4 Affects Multiple Domains of Neuropsychological Functioning in a Sample of Elderly Hispanics.

Apolipoprotein ɛ4 allele (APOEɛ4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), but inconsistencies have arisen in studies with Hispanics. The objective of this study was to explore APOEɛ4 expression and cognitive function in a sample of Panamanian older adults, including healthy controls, mild cognitive impairment, and AD. Participants with at least one copy of APOEɛ4 had a significantly lower performance in global cognition, verbal memory, executive functions, visuospatial abilities, regardless of diagnosis. The present study contributes to the understanding of the association of APOEɛ4 and impairment in specific cognitive domains in elderly Hispanics.

The Panama Aging Research Initiative Longitudinal Study.

The Panama Aging Research Initiative is a cohort study of 423 adults aged ≥65 years recruited from an outpatient geriatric department of Panama's largest public hospital, the Social Security Fund's Dr Arnulfo Arias Madrid Hospital Complex (Complejo Hospitalario Dr Arnulfo Arias Madrid de la Caja de Seguro Social). The study provides the first reports of modifiable and non-modifiable risk factors of cognitive impairment and dementia, as well as various health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and rates of comorbidity. The initial study, conducted September 2012-May 2016, included a clinical interview; physical assessments of body mass index and handgrip strength; and cognitive testing, plus non-fasting blood draws for measurements of genetic (Apolipoprotein E genotype) and blood-based biological markers. Information was collected regarding limitations in activities of daily living, symptoms of depression and fall incidents. A subsample of participants provided cerebrospinal fluid to measure proteins related to Alzheimer's disease; another subsample underwent ultrasonography and electroencephalography. This report describes the general study design and highlights lessons learned and future directions. In particular, drawing on lessons learned from this clinical research, a community-based prospective cohort study is currently under way among older adults in Panama to validate a blood-based biomarker profile for detecting mild cognitive impairment and Alzheimer's disease, as well as risk factors for cognitive decline. KEYWORDS: Dementia, biomarkers, Latin America, aging, cognition, chronic disease, Panama.

Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.