Age, menstruation history, and the brain.

We examined whether late-life depression, including depressive symptoms and antidepressant use, was associated with smaller total brain volume, smaller hippocampal volume, and larger white matter hyperintensity (WMH) volume in a large community-based cohort of old persons without dementia. Within the Washington/Hamilton Height-Inwood Columbia Aging Project (WHICAP), a community-based cohort study in northern Manhattan, 630 persons without dementia (mean age 80 years, SD=5) had volumetric measures of the total brain, hippocampus, and WMH at 1.5 Tesla MRI and data on current depression, defined as a score of 4 or higher on the 10-item Center for Epidemiologic Studies-Depression (CES-D) scale, or use of antidepressants. Multiple linear regression analyses adjusted for age, gender, ethnicity, education, cardiovascular disease history, and MRI parameters showed that subjects with current depression had smaller relative total brain volume (B= −0.86%; 95% CI −1.68 to −0.05%; p<0.05), smaller relative hippocampal volume (B= −0.07ml; 95% CI −0.14 to 0.00ml; p=0.05), and larger relative WMH volume (natural logtransformed B=0.19ml; 95% CI 0.02 to 0.35ml; p<0.05). When examined separately, antidepressant use was significantly associated with smaller total brain, smaller hippocampal, and larger WMH volume, while high CES-D scores were not significantly associated with any of the brain measures, although the direction of association was similar as for antidepressant use. With the caveat that analyses were cross-sectional and we had no formal diagnosis of depression, our findings suggest that in this community-based sample of old persons without dementia, late-life depression is associated with more brain atrophy and more white matter lesions, which was mainly driven by antidepressant use.

Association of mid-life serum lipid levels with late-life brain volumes: The atherosclerosis risk in communities neurocognitive study (ARIC[sbnd]NCS)

Objective: 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. Methods: We aimed to evaluate, cross-sectionally and longitudinally, whether consumption of a diet consist with the MIND diet was associated with larger brain volumes, fewer SBIs and fewer atrophy in the community-based Framinham Heart Study. We included 1,904 participants (mean age 69 (SD, 9)) who completed a brain MRI and a validated food frequency questionnaire (FFQ). The MIND diet consists of 10 healthy and five unhealthy components (range: 0-15). A cumulative MIND diet score was calculated by averaging across three FFQs (exams 5 (1991-1995), 6 (1995-1998), and 7 (1998-2001)). From the total study population, 86 % completed all three FFQs. Brain MRI was performed proximal to exam 7 and again after a mean of 7 years (SD, 1.1) (n=1,317). Total brain volume (TBV), hippocampal volume (HPV), white matter hyperintensity volume (WMHV), expressed as a percentage of total cranial volume, and presence of SBIs were assessed from MRI scans. We used multivariable linear (TBV, HPV and WMHV) and logistic (SBIs) regressions for the cross-sectional analyses, and we analyzed the annualized change of TBV and HPV as atrophy measures using multivariable linear regression. Results: In cross-sectional analyses, higher MIND diet scores were significantly associated with larger TBV (β±SE, +0.09±0.04; p=0.03) after adjustment for basic demographic factors, total daily energy intake, and APOE e4 allele status, but was not associated with HPV (+0.001±0.001; p=0.09), WMHV (-0.01±0.01; p=0.27), SBIs (OR (95%CI), +1.01, 0.92:1.10; p=0.61) or atrophy (TBV, -0.001±0.01; p=0.88; HPV, -0.0003±0.001; p=0.62). After additional adjustments for cardiovascular risk factors the association with TBV was attenuated (+0.05±0.04; p=0.17). Significant interactions were observed for HPV by APOE ε4 status and BMI in the basic model. After stratification by APOE ε4 status, higher MIND diet scores were significantly associated with higher HPV among APOE ε4 non-carriers (+0.002±0.001; p=0.01) but not carriers (n=412). After stratification by BMI, higher adherence to the MIND diet was associated with larger HPV among participants with a BMI above 25 (+0.002±0.001; p=0.01), but not among participants with a BMI below 25. Conclusions: Higher adherence to the MIND diet was not independently associated with brain volume measures, SBIs or brain atrophy in our community cohort as the associations appeared to be mediated by cardiovascular risk factors. In addition, we observed that adherence to the diet was associated with larger brain volume measures in sub groups. Replication is needed to confirm our findings.

BRAIN VOLUME, CEREBRAL β-AMYLOID DEPOSITION, AND AGEING: A STUDY OF OVER 200 INDIVIDUALS BORN IN THE SAME WEEK IN 1946

Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. Children 7-15 years old were recruited for a case-control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = -0.147 (-0.27 to -0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. The aim was to examine whether habitual coffee consumption is associated with differences in brain volumes or the risk odds of dementia or stroke. Methods Prospective analyses of habitual coffee consumption were conducted in 398,646 participants (age 37-73 years) within the UK Biobank, including 17,702 participants with volumetric MRI information. We examined associations between coffee consumption and brain volume using covariate adjusted linear regression, and with odds of dementia and stroke using logistic regression. All participants were free of dementia and stroke at baseline. We obtained 4,333 incident dementia and 6,181 incident stroke cases. Results There were inverse linear associations between coffee consumption and total brain (β per cup -1·42, p = 1·4x10-8), grey matter (-0·92, p = 5·2x10-10), white matter (-0·50, p = 0·002) and hippocampal volumes (-0·01, p = 0·009), but no evidence to support associations with white matter hyperintensity volume (-0·01, p = 0·72). After full covariate adjustment, consumption of > 6 cups/day of coffee was associated with 53% higher odds of dementia compared to consumption of 1-2 cups/day (OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusions High coffee consumption was associated with smaller total brain volumes and increased odds of dementia. Key messages The findings suggest caution at higher levels of coffee consumption, however further studies are required to establish causality, and to explore the clinical relevance of brain volume changes.

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessCardiovascular Risk Factors May Serve as Early Indicator of Cognitive DeclineVabren WattsVabren WattsSearch for more papers by this authorPublished Online:3 Sep 2015https://doi.org/10.1176/appi.pn.2015.8b10AbstractLower total brain, hippocampal, precuneus, and posterior cingulate volumes are associated with cardiovascular risk factors and with impaired cognitive function before the onset of clinical dementia.A study recently published in the journal Radiology suggests that subtle differences in regional brain volumes that appear to be related to cardiovascular risk factors may potentially serve as an early indicator of cognitive decline before the onset of dementia.simone mescolini/ShutterstockResearchers from the Keck School of Medicine at the University of Southern California and the University of Texas Southwestern Medical Center led a retrospective study to investigate modifiable cardiovascular risk factors (alcohol consumption, smoking, diabetes, and obesity) associated with regional brain volume changes and their association with preclinical deficits in cognitive performance. The specific brain regions studied included the hippocampus, prenuceus, and posterior cingulate cortex—all brain regions involved with cognition.“We already know that vascular risk factors damage the brain and can result in cognitive impairment,” Kevin King, M.D., an assistant professor of radiology at the University of Southern California, said in a press statement. “But our findings give us a more concrete idea about the relationship between specific vascular risk factors and brain health.”For the study, the researchers analyzed data from 1,629 participants who were aged 25 to 73 and enrolled in the Dallas Heart Study from 2000 to 2002. Participants’ cardiovascular risk factors were evaluated in an initial baseline visit; brain volumes and cognitive function were assessed seven years later by, respectively, magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA).The results showed that alcohol consumption and diabetes were associated with smaller total brain volume, and smoking and obesity were associated with reduced volumes in the posterior cingulate cortex. Lower hippocampal volume was associated with previous alcohol consumption and smoking, and lower precuneus volume correlated with alcohol consumption, obesity, and high fasting blood glucose numbers.Low total scores for MoCA were associated with reduced posterior cingulate volume in participants under 50 and with reduced hippocampal and precuneus volumes in those 50 and over.“Our findings reveal that lower total brain, hippocampal, precuneus, and posterior cingulate volumes are associated with cardiovascular risk factors and with impaired cognitive performance before the onset of clinical dementia. … even in participants younger than 50 years,” the researchers noted. The researchers concluded that subtle differences in regional brain volumes in midlife may serve as a biomarker for brain insult before the onset of dementia.“In the future, we may be able to provide patients with useful and actionable information about the impact different risk factors may be having on their brain health during routine clinical imaging,” King stated. The study was funded by the National Institutes of Health. ■“Cardiovascular Risk Factors Associated With Smaller Brain Volumes in Regions Identified as Early Predictors of Cognitive Decline” can be accessed here. ISSUES NewArchived

Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. Objectives We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. Methods We conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37–73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression. Results There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (P non-linearity = 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusion High coffee consumption was associated with smaller total brain volumes and increased odds of dementia.

Global brain atrophy but not hippocampal atrophy is related to type 2 diabetes

Physical activity and brain volumes in older adults: The Washington Heights‐Inwood Columbia Aging Project (WHICAP)

BackgroundHigher Mediterranean‐ DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community‐based cohort. We investigated cross‐sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community‐based cohorts.MethodWe analyzed data from 3130 dementia‐, stroke‐ and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort. Individuals completed a brain magnetic resonance imaging (MRI) scan, and a validated food frequency questionnaire (FFQ) (ARIC, CHS, FOS, RS), 24h dietary recall (3C), or an extensive food list (SHIP). The MIND diet consists of ten healthy (e.g. green leafy vegetables, berries and fish) and five unhealthy (e.g. cheese, red meat and products and fast fried foods) components. Outcomes from brain MRI included TBV, total grey matter volume (TGMV), hippocampal volume (HPV), and WMHV. We used multivariable linear regression to relate MIND diet adherence to the outcomes. Results were combined in meta‐analysis using fixed effects and random effects models.ResultHigher MIND diet scores (score range: 0‐15) were associated with larger HPV (beta = 0.015, 95% confidence interval = 0.004 to 0.026, cm³ per one unit MIND diet score increase) after adjustment for age, age squared, sex, time from clinical exam to brain MRI exam, total intracranial volume and energy intake, but not with TBV, TGMV and WMHV. Heterogeneity between studies was low (I2 = 0% TBV, TGMV, HPV) to moderate (I2 = 44% WMHV).ConclusionIn cross‐sectional analyses, higher MIND diet scores were associated with larger HPV, but not with other brain volume measures. It might be that HPV was a more sensitive marker of brain health in the populations under study. Future studies are encouraged to examine the associations between the MIND diet and amyloid and tau positron emission tomography (PET) imaging to elucidate whether a relationship between the MIND diet and dementia pathologies exists.

Low soluble amyloid-β 42 is associated with smaller brain volume in Parkinson's disease

To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

To estimate the association between hippocampal and total brain volume and the course of depressive symptoms over eight years of follow-up in patients with a history of vascular disease. Within the SMART-Medea study, 636 participants (62 ± 10 years) had a 1.5-tesla brain MRI obtaining hippocampal and total brain volumes. Depressive symptoms were assessed with the Patient Health Questionnaire-9 biannually during eight-year follow-up. Generalized estimating equation models with robust standard errors were used to assess the associations of hippocampal and total brain volumes with depressive symptoms during follow-up adjusting for age, sex, education, and intracranial volume. An interaction term between volume and time (6-month intervals) was included to examine whether the course of depressive symptoms differed according to hippocampal and total brain volume. The mean PHQ-9 score was 2.8 ± 3.5. Smaller hippocampal volumes were associated with an increasing course of depressive symptom levels, while larger volumes were associated with decreasing levels (P-value interaction = 0.07). Smaller total brain volume was associated with consistently higher levels of depressive symptoms, but not with change in course of depressive symptoms (P-value interaction = 0.45). Smaller hippocampal volume but not total brain volume is associated with poorer course of depressive symptoms over eight years of follow-up.

To test whether red blood cell (RBC) levels of marine omega-3 fatty acids measured in the Women's Health Initiative Memory Study were related to MRI brain volumes measured 8 years later. RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women's Health Initiative Memory Study. The endpoints were total brain volume and anatomical regions. Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy, time since randomization, demographics, intracranial volume, and cardiovascular disease risk factors. In fully adjusted models, a 1 SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total brain volume while EPA was less so (p = 0.11). There were no correlations between ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully adjusted models. Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034). A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later. While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy. Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy.