Search

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65–97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18–63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans. • In animal models, aging-related changes in the hypothalamus drive brain aging. • The role of the hypothalamus in neurocognitive aging in humans is unknown. • We show that hypothalamic microstructure is altered with aging in older adults. • Hypothalamic microstructure is associated with cortical thickness and cognition. [ABSTRACT FROM AUTHOR]

Background: Very few studies have explored the utility of subjective cognitive complaints (SCCs) in primary care settings.Objective: We aim to investigate associations between SCCs (item-level), objective cognitive function (across domains and global), and mood in a diverse primary care population, including subjects with mild cognitive impairment.Methods: We studied 199 (75.9%females; 57.8%Hispanics; 42.2%African Americans) older adults (mean age 72.5 years) with memory concerns at a primary care clinic. A five-item SCC questionnaire, and objective cognitive assessments, including the Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale, were administered.Results: Logistic regression analyses showed associations between SCC score and depressive symptoms. A memory-specific ("memory worsening") SCC predicted scores on the MoCA (p = 0.005) in Hispanics.Conclusion: SCCs are strongly linked to depressive symptoms in African Americans and Hispanics in a primary care setting; a specific type of SCC is related to global cognitive function in Hispanics. [ABSTRACT FROM AUTHOR]

Aging is a complex trait characterized by a diverse spectrum of endophenotypes. By utilizing the SomaScan® proteomic platform in 1,025 participants of the LonGenity cohort (age range: 65–95, 55.7% females), we found that 754 of 4,265 proteins were associated with chronological age. Pleiotrophin (PTN; β[SE] = 0.0262 [0.0012]; p = 3.21 × 10−86), WNT1‐inducible‐signaling pathway protein 2 (WISP‐2; β[SE] = 0.0189 [0.0009]; p = 4.60 × 10−82), chordin‐like protein 1 (CRDL1; β[SE] = 0.0203[0.0010]; p = 1.45 × 10−77), transgelin (TAGL; β[SE] = 0.0215 [0.0011]; p = 9.70 × 10−71), and R‐spondin‐1(RSPO1; β[SE] = 0.0208 [0.0011]; p = 1.09 × 10−70), were the proteins most significantly associated with age. Weighted gene co‐expression network analysis identified two of nine modules (clusters of highly correlated proteins) to be significantly associated with chronological age and demonstrated that the biology of aging overlapped with complex age‐associated diseases and other age‐related traits. The correlation between proteomic age prediction based on elastic net regression and chronological age was 0.8 (p < 2.2E−16). Pathway analysis showed that inflammatory response, organismal injury and abnormalities, cell and organismal survival, and death pathways were associated with aging. The present study made novel associations between a number of proteins and aging, constructed a proteomic age model that predicted mortality, and suggested possible proteomic signatures possessed by a cohort enriched for familial exceptional longevity. [ABSTRACT FROM AUTHOR]

Introduction: Language acculturation is the process by which a bilingual individual obtains proficiency and comfort in speaking a new language while maintaining fluency in their native language. Considering the degree of language acculturation in bilingual patients is essential to choosing appropriate tests and interpreting neuropsychological assessment. The Language Acculturation Meter™ (LAM) was created for native Spanish speakers who are bilingual in English to aid in selecting and interpreting verbally-administered assessments. While the LAM was created to be completed as an interview, a Spanish version of the form exists and can be given to patients to complete independently. We sought to evaluate the feasibility and utility of self-administered LAM in a clinical older adult population in NY State. Methods: The LAM was given to Spanish-speaking older adults and their caregivers as part of their clinical neuropsychological evaluation at Montefiore's Memory Disorders Centers. 16 patient and caregiver dyads completed the LAM in either English or Spanish. Results: Patient ages ranged from 67 to 83; 75% of the patients were female, and 56% self-identified as bilingual. 18% of patients completed the LAM without caregiver assistance. Dyads did not comment on the form, but early qualitative feedback suggests that some had difficulty understanding how to complete aspects of the LAM, and others found that some items on the LAM did not apply to them. Conclusions: The LAM is a previously validated interview tool that requires further research to determine if it can be used as a self-report questionnaire in clinical populations, including older adults with cognitive complaints. [ABSTRACT FROM AUTHOR]

Objective: The Symbol Digit Modalities Test (SDMT) is a task of processing speed and executive functioning that is widely used to evaluate individuals with Multiple Sclerosis (MS) and has been shown to predict various instrumental activities of daily living. The relationship between SDMT and daily functioning has not been well explored in the aging population. The Activities of Daily Living-Prevention Instrument (ADL-PI) is a self-report measure that assesses changes in functioning and instrumental activities of daily living (IADLs). We evaluate the relationship between SDMT and ADL-PI in older adults with subjective cognitive complaints in an urban, multi-ethnic, primary care population in Bronx, New York. Methods: 300 participants (50.7% Hispanic, 43.7% non-Hispanic Black; 37% assessed in Spanish) completed the SDMT and ADL-PI as part of a larger study seeking to improve detection of cognitive impairment in primary care. The mean age of the sample was 71.35 ± 5.76 years and participants had a mean 12.26 ± 3.76 years of education. Pearson correlations were used to examine the relationship between SDMT and IADLs. Results: SDMT performance was weakly albeit significantly correlated with self-report of functional difficulties on the ADL-PI (r = −0.312, p < 0.001). The relationship between SDMT (Range = 1–51, M = 25.39) and ADL-PI was significant in both English (p < 0.0011) and Spanish (p = 0.004) speaking participants and remained significant when controlling for age, education, and depression (p = 0.002). Conclusion: Consistent with MS literature, the SDMT is a useful tool for predicting self-report of instrumental activities of daily living of older adults with cognitive concerns. [ABSTRACT FROM AUTHOR]

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition – not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life. • Cognitive reserve permits people to cope with brain pathology and delay dementia. • Cognitive reserve can be accrued from cognitive, physical, and social activities. • Cognitive reserve slowed age-related cognitive decline – not gait speed decline. • Results were consistent across cognitive, physical, and social reserve proxies. [ABSTRACT FROM AUTHOR]

While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults (n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05–1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680–0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08–2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004–1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29–0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span. [ABSTRACT FROM AUTHOR]