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Results for “Midlife”

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At least 19 recordsLinked to original sources

PubMed2022

Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

Knowledge of a person's risk for Alzheimer's disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer's Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from -0.08 to -0.11), tested cognitive deficits (β's from -0.36 to -0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from -0.18 to -0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

Alzheimer’s disease↗

PubMed2025

Measures of retinal health successfully capture risk for Alzheimer's disease and related dementias at midlife.

BackgroundIdentification of at-risk individuals who would benefit from early intervention for Alzheimer's disease and related dementias (ADRD) is critical as new treatments are developed. Measures of retinal health could offer accessible and low-cost indication of pre-morbid disease risk, but their association with ADRD risk is unknown.ObjectiveTo determine whether midlife retinal neuronal and microvascular measures are associated with ADRD risk-index scores and individual domains of ADRD risk.MethodsData were from the Dunedin Multidisciplinary Health and Development Study, a population-representative longitudinal New Zealand-based birth cohort study. 94.1% (N = 938) of living Study members were seen at age 45 (2017-2019). Retinal neuronal (retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL)) and microvascular (arterioles and venules) measures were used as predictors. Outcome measures were four top ADRD risk indexes (CAIDE, LIBRA, Lancet, and ADU-ADRI), and a comprehensive midlife ADRD risk index, the DunedinARB.ResultsPoorer retinal microvascular health (narrower arterioles and wider venules) was associated with greater ADRD risk (βs = 0.16-0.31; ps < 0.001). Thinner RNFL was modestly associated with higher ADRD risk (βs = 0.05-0.08; ps = 0.02-0.13). Follow-up tests of distinct domains of ADRD risk indicated that while RNFL associations reflected cardiometabolic risk only, microvascular measures were associated with diverse ADRD risk factors.ConclusionsMeasures of retinal health, particularly microvascular measures, successfully capture ADRD risk across several domains of known risk factors, even at the young midlife age of 45 years. Retinal microvascular imaging may be an accessible, scalable, and relatively low-cost method of assessing ADRD risk among middle-aged adults.

Humans↗

PubMed2024

Characterizing midlife-onset alcohol dependence: Implications for etiology, prevention, and healthy aging.

We evaluated the developmental epidemiology of midlife-onset alcohol dependence (AD) in the Dunedin Study (N=1,037), a population-representative cohort followed across five decades. At ages 18, 21, 26, 32, 38, and 45, past-year AD prevalence was 11.0%, 18.4%, 13.6%, 8.1%, 9.6%, and 11.3%, respectively. As expected, relative to never-diagnosed individuals, those with early-onset AD (first diagnosis: age-18 or age-21, prevalence=22.9%) were distinguished by a range of early-life and adult correlates. Individuals with midlife-onset AD (first diagnosis: age-38 or age-45, prevalence=5.6%) were distinguished by fewer early-life correlates, but exhibited a family history of AD, and adolescent dysregulation and marijuana-use. They were characterized by an array of adult correlates, including internalizing disorders, mental-health treatment-contact, criminal-behavior, perceived-stress, coping-by-drinking, lower likelihood of marriage and parenthood, and reduced preparedness for old age. They also experienced more adult alcohol-related impairment than the early-onset group. Results can guide efforts to reduce midlife alcohol-related problems and support healthy aging.

Journal Article↗

PubMed1979

Midlife concerns of women: implications of the menopause.

Midlife has received recent attention but is still difficult to define. Women's developmental phases are most appropriately understood as different from men's, with a complex integration of biological context, family development and roles, and individual development. Menopause has been considered a determining event, and a variety of symptoms have been attributed to menopausal changes. Emerging data indicate that menopause does not appear to be responsible for most of the symptoms. Midlife stresses are the result of a combination of personal, family, social, and biological variables, with postmenopausal development an important phase.

Adjustment Disorders↗

PubMed1979

Women in midlife: decisions, rewards, and conflicts related to work and careers.

The author discusses the role of an occupation in the psychic economy of women in midlife and the diagnostic and therapeutic function of attention to work-related issues. Clinical examples are grouped according to commonly encountered patterns as these result from prevous developmental choices and as they show some of the possible repercussions during the middle years. In psychotherapy with midlife women it is important to address work-related issues in terms of the interplay among previous development, age-specific factors, and social realities and changes as well as neurotic factors.

Adult↗

PubMed2026

Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.

BACKGROUND: Studies linking mitochondrial DNA (mtDNA) variants to cognition yielded inconsistent findings, and the underlying mechanisms remain unclear. We investigated whether mtDNA heteroplasmic variants were associated with cognitive outcomes, including the Montreal Cognitive Assessment (MoCA), in 197 late midlife adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with complete data. METHODS: MtDNA was sequenced from blood using targeted deep sequencing. Adjusted linear and mixed-effects models examined the associations by functional regions, genes, total variant burden, nonsynonymous variants, and control regions. RESULTS: Heteroplasmic variants in the control region (β = -0.44, 95% CI: -0.83, -0.05, p = 0.027) and transfer RNA (tRNA) genes (β = -1.34, 95% CI: -2.58, -0.11, p = 0.034) were associated with MoCA baseline scores. Individual variants in cytochrome c oxidase subunit 1 (CO1) (β = -1.51, 95% CI: -2.54, -0.47, p = 0.005), NADH dehydrogenase subunit 1 (ND1) (β = -2.63, 95% CI: -4.56, -0.70, p = 0.008), and Displacement Loop (D-LOOP2) (β = -2.25, 95% CI: -4.20, -0.30, p = 0.025) was associated with reduced baseline MoCA scores. The ND6 (β = −1.23, 95% CI: −2.09, − 0.37, p = 0.006), ND4 (β = −1.11, 95% CI: −2.02, − 0.20, p = 0.018), ATP Synthase Membrane Subunit 8 (ATP8; β = −1.38, 95% CI: −2.63, − 0.13, p = 0.031), and D-LOOP1 (β = −0.61, 95% CI: −1.20, − 0.01, p = 0.045) genes suggested a potential association with executive function. Longitudinal Animal Fluency Test (AFT) scores were inversely associated with heteroplasmic variants in coding regions (β = -0.10, 95% CI: -0.19, -0.006, p = 0.049), the total number of variants (β = -0.06, 95% CI: -0.11, -0.003, p = 0.037) and total nonsynonymous variants (β = -0.11, 95% CI: -0.21, -0.01, p = 0.040). Variants in the control region were associated with the greatest decline in verbal fluency (β = −0.20, 95% CI: −0.39 to − 0.002, p = 0.049). No associations were observed between mitochondrial variants and verbal memory performance or the MoCA composite scores. CONCLUSIONS: Our study indicates that mitochondrial variants measured in blood may provide insight into cognitive function during midlife. However, additional studies are needed to validate these associations and to address potential power limitations in our study.

Humans↗

PubMed1979

Marriage and midlife: the impact of social change.

This paper considers the impact of social change on marriage in the midlife period. Issues which ordinarily require adaptation in midlife e.g., awareness of the finiteness of time, the limits of options and the necessity to reassess goals and deal with losses are affected by societal changes. These changes include increased numbers of dual career families and a decreased birth rate. Marital partners must integrate these changes into their lives. The process of adaptation may be stressful and result in symptoms such as depression, anxiety, somatic complaints of sexual problems. Illustrative clinical examples and treatment approaches are provided.

Adaptation, Psychological↗

PubMed2024

Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

Humans↗

PubMed2025

Differential methylation clock ages across buffy coat (BC), peripheral blood mononuclear cells (PBMC), and saliva in individuals approaching midlife.

Understanding epigenetic aging prior to midlife is gaining interest as a potentially intervenable period to address factors that influence health and cognitive aging. Epigenetic changes associated with aging may point to differential biological aging rates; however, methylation profiles may not be substitutable across tissues. We compared DNA methylation in three tissues collected in 91 siblings and twins from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife1): saliva, buffy coat (BC), and peripheral blood mononuclear cells (PBMC). Overall, across five methylation clocks and two blood-derived and one saliva-derived tissues, moderate to strong associations between chronological age and methylation ages were observed. Moreover, PBMC methylation age values correlate more strongly with BC values (Spearman r = 0.66 - 0.87), whereas saliva showed weaker correlations with either form of blood-derived measures (Spearman r = 0.25 - 0.69) although still moderate to strong magnitudes. Saliva demonstrated significantly older methylation ages across four of five clocks, whereas PBMC and BC did not differ. Twins were more strongly correlated for BC and PBMC derived clocks with weaker and inconsistent patterns among Saliva clocks. DunedinPACE age acceleration showed no significant tissue differences and on average demonstrated the largest divergence of similarity between monozygotic (MZ) versus dizygotic (DZ) twins (rMZ= .56, rDZ= .21). In summary, saliva-derived methylation is not a direct substitute for blood-derived methylation whereas blood-derived methylation values were comparable across buffy coat and peripheral blood mononuclear cell tissues.

age acceleration↗

PubMed1976

Midlife marriage: sex differences in evaluation and perspectives.

Perceptions of marital relations are examined in a white middle and lower-middle class sample representing three life stages: newlyweds, middle-aged parents facing the empty nest, and persons about to retire. Descriptions of spouses are analyed in terms of positive/negative evaluations and the respective importance given to role and interpersonal components of the marital relationship. Middle aged respondents were shown to place greater emphasis on role performance than did the remaining groups, and middle-aged women gave the least positive evaluations of marriage. Midlife marital satisfaction is examined in relationship to affect toward children, socioeconomic status, value orientations, and life satisfaction.

Adult↗

PubMed1979