The aging brain: risk factors and interventions for long term brain health in women.

PURPOSE OF REVIEW: Poor cognitive aging and dementia pose a significant public health burden, and women face unique risks compared to men. Recent research highlights the role of genetics, menopause, chronic disease, and lifestyle in risk and resilience in women\u27s cognitive aging. This work suggests avenues for clinical action at midlife that may change the course of brain health in aging. RECENT FINDINGS: Studies indicate women\u27s risk for poor cognitive aging relates in part to hormone changes at menopause, a time when memory, brain structure and function, and Alzheimer\u27s pathology may be observed in women and not men. Medical and lifestyle risks including diabetes, hypertension, and low physical activity also contribute to women\u27s unique risks. At the same time, literature on resilience suggests women may benefit from lifestyle and chronic disease intervention, possibly more than men. Current studies emphasize the importance of interacting genetic and lifestyle risks, and effects of social determinants of health. SUMMARY: Women have greater risk than men for poor cognitive aging; however, by treating the whole person, including genetics, lifestyle, and social environment, clinicians have an opportunity to support healthy cognitive aging in women and reduce the future public health burden of dementia

Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume

Abstract Background Alzheimer’s disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A+) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI). Methods Seven hundred forty-two participants with NC and participants with eMCI from the Alzheimer’s Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included. All had baseline florbetapir PET measured, and 526 had screening visit HV measured. Regression moderation models were used to examine whether A+ effects on Rey Auditory Verbal Learning Test learning and delayed recall and right and left HV (adjusted for total intracranial volume) were moderated by diagnosis and sex. Age, cognition at screening, education, and apolipoprotein E ε4 carrier status were controlled. Results Women with A+, but not those with florbetapir PET amyloid negative (A-),eMCI showed poorer learning. For women with NC, there was no relationship of A+ with learning. In contrast, A+ men trended toward poorer learning regardless of diagnosis. A similar trend was found for verbal delayed recall: Women with A+, but not A-, eMCI trended toward reduced delayed recall; no effects were observed for women with NC or for men. Hippocampal analyses indicated that women with A+, but not those with A−, eMCI, trended toward smaller right HV; no significant A+ effects were observed for women with NC. Men showed similar, though nonsignificant, patterns of smaller right HV in A+ eMCI, but not in men with A− eMCI or NC. No interactive effects of sex were noted for left HV. Conclusions Women with NC showed verbal learning and memory scores robust to A+, and women with A+ eMCI lost this advantage. In contrast, A+ impacted men’s scores less significantly or not at all, and comparably across those with NC and eMCI. Sex marginally moderated the relationship of A+ and diagnosis with right HV, such that women with NC showed no A+ effect and women with A+ eMCI lost that advantage in neural integrity; the pattern in men was less clear. These findings show that women with A+ eMCI (i.e., prodromal AD) have differential neural and cognitive decline, which has implications for considering sex in early detection of AD and development of therapeutics

Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure.

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction

Greater externalizing behavior in preschool correlates with smaller male amygdala volume.

<p>A) Representative coronal view of the amygdala with key neuroanatomical landmarks denoted: AMG = amygdala; EC = entorhinal cortex; HH = hippocampal head; OT = optic tract; TLV = temporal horn of the lateral ventricle; TLWM = temporal lobe white matter. B) Correlation of preschool externalizing with amygdala volumes (upper panel: male r = -0.653, <i>p</i> = 0.000029; female r = -0.088, <i>p</i> = 0.578).</p

Hippocampus tracing landmarks as viewed on coronal native space images.

<p>Panels A-H, viewed from top to bottom and left to right in each row, show anterior to posterior progression through the hippocampus. Insets show areas of focus on full-brain sections (black box). An example region of interest is traced in black and labeled by hippocampal subregion: hippocampal head (HH), body (HB), and tail (HT). AMG = amygdala; FX = fornix; EC = entorhinal cortex; LV = lateral ventricle; PG = parahippocampal gyrus; PT = pulvinar of the thalamus; QC = quadrigeminal cistern; TLV = temporal horn of the lateral ventricle; UN = uncus.</p

Descriptive statistics for raw computed and hand-traced neural volumes.

<p>Descriptive statistics for raw computed and hand-traced neural volumes.</p

Greater preschool externalizing behavior relates to smaller right angular gyrus and temporoparietal junction, across genders.

<p>A) Coronal, sagittal, and axial views; coordinates indicate cluster peak, within the angular gyrus. B) Correlation of individual subject cluster volume and preschool externalizing behavior (full sample: r = -0.536, <i>p</i> = 0.000000705; male: r = -0.584, <i>p</i> = 0.000355; female r = -0.607, <i>p</i> = 0.0000199).</p