Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.

Introduction: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.

Methods: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.

The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men.

Introduction: Despite their increased application, the heritability of Alzheimer's disease (AD)-related blood-based biomarkers remains unexplored.

Methods: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t-tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.

The Impact of Genes and Environment on Brain Ageing in Males Aged 51 to 72 Years.

Magnetic resonance imaging data are being used in statistical models to predicted brain ageing (PBA) and as biomarkers for neurodegenerative diseases such as Alzheimer's Disease. Despite their increasing application, the genetic and environmental etiology of global PBA indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown.

Alcohol use and cognitive aging in middle-aged men: The Vietnam Era Twin Study of Aging.

Objective: To determine associations of alcohol use with cognitive aging among middle-aged men.

Method: 1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003-2007 to 2016-2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1-4 drinks in past 14 days), light (5-14 drinks), moderate (15-28 drinks), and at-risk drinkers (>28 drinks in past 14 days).

Paradoxical cognitive trajectories in men from earlier to later adulthood.

Because longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at 3 VETSA assessments beginning at average age 56. The same GCA index was used throughout.

Long-term associations of cigarette smoking in early mid-life with predicted brain aging from mid- to late life.

Background And Aims: Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid-life would have older than predicted brain age 16-28 years later.

Lifestyle and the aging brain: interactive effects of modifiable lifestyle behaviors and cognitive ability in men from midlife to old age.

We examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40.

12-year prediction of mild cognitive impairment aided by Alzheimer's brain signatures at mean age 56.

Neuroimaging signatures based on composite scores of cortical thickness and hippocampal volume predict progression from mild cognitive impairment to Alzheimer's disease. However, little is known about the ability of these signatures among cognitively normal adults to predict progression to mild cognitive impairment. Towards that end, a signature sensitive to microstructural changes that may predate macrostructural atrophy should be useful.

MRI-assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction.

Introduction: The locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.

Methods: Participants were 481 men (ages 62 to 71.

Associations between depression and cardiometabolic health: A 27-year longitudinal study.

Background: Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.

Methods: The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse ('baseline') and the longitudinal Vietnam Era Twin Study of Aging ('follow-up').

Interaction between Alcohol Consumption and Apolipoprotein E (ApoE) Genotype with Cognition in Middle-Aged Men.

Objective: Heavy alcohol consumption is associated with poorer cognitive function in older adults. Although understudied in middle-aged adults, the relationship between alcohol and cognition may also be influenced by genetics such as the apolipoprotein (ApoE) ε4 allele, a risk factor for Alzheimer's disease. We examined the relationship between alcohol consumption, ApoE genotype, and cognition in middle-aged adults and hypothesized that light and/or moderate drinkers (≤2 drinks per day) would show better cognitive performance than heavy drinkers or non-drinkers.

Empty mast cell syndrome: fallacy or fact?

Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as 'empty mast cell (MC) syndrome', is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis.

Posttraumatic stress symptom persistence across 24 years: association with brain structures.

Posttraumatic stress disorder (PTSD) is known to persist, eliciting early medical co-morbidity, and accelerated aging. Although PTSD diagnosis has been found to be associated with smaller volume in multiple brain regions, posttraumatic stress (PTS) symptoms and their associations with brain morphometry are rarely assessed over long periods of time. We predicted that persistent PTS symptoms across ~24 years would be inversely associated with hippocampal, amygdala, anterior cingulate volumes, and hippocampal occupancy (HOC = hippocampal volume/[hippocampal volume + inferior lateral ventricle volume]) in late middle age.

Mediators of the Effect of Childhood Socioeconomic Status on Late Midlife Cognitive Abilities: A Four Decade Longitudinal Study.

Background And Objectives: Childhood socioeconomic status (cSES) is found to predict later-life cognitive abilities, yet the mechanisms underlying these associations remain unclear. The objective of this longitudinal study was to examine the direct and indirect paths through which cSES influences late midlife cognitive outcomes.

Research Design And Methods: Participants were 1,009 male twins in the Vietnam Era Twin Study of Aging (VETSA).

Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects.

Introduction: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI).

Methods: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging.

A longitudinal twin study of general cognitive ability over four decades.

In this longitudinal study we examined the stability of general cognitive ability (GCA), as well as heterogeneity and genetic and environmental influences underlying individual differences in change. We investigated GCA from young adulthood through late midlife in 1,288 Vietnam Era Twin Study of Aging participants at ages ∼20, ∼56, and ∼62 years. The correlations among the 3 occasions ranged from .

White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.

Genetic and environmental architecture of changes in episodic memory from middle to late middle age.

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain.

Genetic complexity of episodic memory: a twin approach to studies of aging.

Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if "memory is memory" and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR).

Post-traumatic stress symptoms and adult attachment: a 24-year longitudinal study.

Objectives: Attachment theory has become a key framework for understanding responses to and consequences of trauma across the life course. We predicted that more severe post-traumatic stress (PTS) symptoms at age 37 years would be associated with insecure attachment at age 55 and with worse PTS symptoms 24 years later at age 61, and that age 55 attachment would mediate the influence of earlier PTS symptoms on later symptoms.

Design: Data on PTS self-reported symptoms were available for 975 community-dwelling participants from the longitudinal Vietnam Era Twin Study of Aging at ages 37 and 61 years.

Interaction of APOE genotype and testosterone on episodic memory in middle-aged men.

Age-related changes in testosterone are believed to be a key component of the processes that contribute to cognitive aging in men. The APOE-ε4 allele may interact with testosterone and moderate the hormone's association with cognition. The goals of the present study were to examine the degree to which free testosterone is associated with episodic memory in a community-based sample of middle-aged men, and examine the potential interaction between free testosterone and the APOE-ε4 allele.

Gene-environment interaction of ApoE genotype and combat exposure on PTSD.

Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia.

Adult cognitive ability and socioeconomic status as mediators of the effects of childhood disadvantage on salivary cortisol in aging adults.

In this longitudinal study we investigate the influence of childhood disadvantage on midlife hypothalamic-pituitary-adrenal (HPA) axis regulation. Two mechanisms by which early life stress may affect later pathophysiology are through its influence on cognitive functioning or later socioeconomic (SES) disadvantage. We predicted that individual differences in young adult cognitive ability and midlife SES would mediate the influence of childhood disadvantage on midlife cortisol.

Genetic and environmental influences of daily and intra-individual variation in testosterone levels in middle-aged men.

Background: Testosterone regulates numerous physiological processes, and evidence suggests that it plays a critical role in male aging. It has yet to be determined whether the heritability of testosterone varies in accordance with its diurnal rhythm. Similarly, it is unclear whether changes in testosterone level throughout the day are genetically influenced.