Adrienne O’Donnell

= 104), tracked Aβ-associated spread of TAU from this site first to nearby neocortex of the temporal lobe and then to extratemporal regions. Greater rate of TAU spread was associated with baseline measures of both global Aβ burden and medial temporal lobe TAU. These findings are consistent with clinicopathological correlation studies of Alzheimer's tauopathy and enable precise tracking of AD-related TAU progression for natural history studies and prevention therapeutic trials.

OBJECTIVE: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults. METHODS: 328 CN participants from the Framingham Study (mean age = 57 years (±10 years), 161 women, of whom, 104 were post-menopausal) underwent tau and β-amyloid (Aβ)-PET neuroimaging. We examined global Aβ-PET, and tau-PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status-related differences in each region-of-interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. RESULTS: Women exhibited higher tau-PET signal (p < 0.002), and global Aβ-PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age-matched men, post-menopausal women showed significantly higher tau-PET signal in parieto-occipital regions (p < 0.0001). By contrast, no differences in tau-PET signal existed between pre-menopausal women and men. Aβ-PET was not associated with menopausal status or age. Neither Aβ-PET nor APOEε4 status moderated sex or menopause associations with tau-PET. INTERPRETATION: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau-PET burden, with tau first appearing post-menopause. Sex and menopause differences consistently appeared in middle frontal and parieto-occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause-related tau vulnerability may be independent of AD-related pathways. ANN NEUROL 2022;92:11-22.

Importance: Cognitive resilience refers to the general capacity of cognitive processes to be less susceptible to differences in brain structure from age- and disease-related changes. Studies suggest that supportive social networks reduce Alzheimer disease and related disorder (ADRD) risk by enhancing cognitive resilience, but data on specific social support mechanisms are sparse. Objective: To examine the association of individual forms of social support with a global neuroanatomical measure of early ADRD vulnerability and cognition. Design, Setting, and Participants: This retrospective cross-sectional analysis used prospectively collected data from Framingham Study participants without dementia, stroke, or other neurological conditions who underwent brain magnetic resonance imaging and neuropsychological testing at the same visit. Data from this large, population-based, longitudinal cohort were collected from June 6, 1997, to December 13, 1999 (original cohort), and from September 11, 1998, to October 26, 2001 (offspring cohort). Data were analyzed from May 22, 2017, to June 1, 2021. Exposures: Total cerebral volume and, as a modifying exposure variable, self-reported availability of 5 types of social support measured by the Berkman-Syme Social Network Index. Main Outcomes and Measures: The primary outcome was a global measure of cognitive function. Cognitive resilience was defined as the modification of total cerebral volume's association with cognition, such that smaller β estimates (presented in SD units) indicate greater cognitive resilience (ie, better cognitive performance than estimated by lower total cerebral volume). Results: The study included 2171 adults (164 in the original cohort and 2007 in the offspring cohort; mean [SD] age, 63 [10] years; 1183 [54%] female). High listener availability was associated with greater cognitive resilience (β = 0.08, P < .001) compared with low listener availability (β = 0.20, P = .002). Overall findings persisted after adjustment for potential confounders. Other forms of social support were not significant modifiers (advice: β = -0.04; P = .40 for interaction; love-affection: β = -0.07, P = .28 for interaction; emotional support: β = -0.02, P = .73 for interaction; and sufficient contact: β = -0.08; P = .11 for interaction). Conclusions and Relevance: The results of this cross-sectional cohort study suggest that social support in the form of supportive listening is associated with greater cognitive resilience, independently modifying the association between lower total cerebral volume and poorer cognitive function that would otherwise indicate increased ADRD vulnerability at the preclinical stage. A refined understanding of social support mechanisms has the potential to inform strategies to reduce ADRD risk and enhance cognitive resilience.

BACKGROUND: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy. OBJECTIVE: We evaluated whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study. METHODS: 2,092 participants (mean±SD, age 61±9) completed Food Frequency Questionnaires, averaged across a maximum of 3-time points (examination cycles 5, 6, and 7), cognitive testing at examination cycle 7 (present study baseline: 1998-2001) and after a mean±SD of 6.6±1.1 years from baseline (n = 1,584). A subset of participants also completed brain magnetic resonance imaging (MRI) at examination cycle 7 (n = 1,904). In addition, participants with dementia, stroke, and other relevant neurological diseases such as significant head trauma, subdural hematoma, or multiple sclerosis were excluded from the analyses. RESULTS: Higher MIND diet scores were associated with better global cognitive function (β±SE,+0.03SD±0.01; p = 0.004), verbal memory, visual memory, processing speed, verbal comprehension/reasoning, and with larger total brain volume (TBV) following adjustments for clinical, lifestyle and demographic covariates, but not with other brain MRI measures (i.e., hippocampal volume, lateral ventricular volume, white matter hyperintensity volume, and SBIs) or cognitive decline. CONCLUSION: Higher MIND diet scores associated with better cognitive performance and larger TBV at baseline, but not with cognitive decline. Clinical trials are needed to ascertain whether adopting the MIND diet affects trajectories of cognitive decline.

Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. 133Xe blood flow techniques, transcranial Doppler, and SPECT have all been employed to investigate hemodynamic changes during migraine aura. PET has been useful in the study of migraine without aura, with findings of increased blood flow related to pain in cortical areas and in the medial brainstem. Currently, three functional MRI imaging techniques are being used in migraine research. Diffusion-weighted imaging has shown normal findings in measures of the ability of neurons to maintain osmotic gradients. Studies using perfusion-weighted imaging have shown alterations in relative cerebral blood flow (CBF), relative cerebral blood volume, and mean transit time during migraine visual aura. The blood oxygen level-dependent technique can supply information related to neuronal activation during acute migraine aura. MRS has been used with mixed success to look for evidence of abnormal energy metabolism in the brains of migraineurs. Magnetoencephalography studies support the presence of a spreading depression-like phenomenon in migraine with aura. Two groups have used transcranial magnetic stimulation to assess whether neurons in the occipital cortex are hyperexcitable, predisposing patients to develop aura symptoms. Despite conflicting findings, migraine with visual aura appears to be generally associated with transient decreases in regional CBF.