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Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study
Abstract
Objectives
Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife.
Methods
In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume.
Results
Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (β = –5.35 mL/year) than in men (β = –4.77 mL/year). Similar age–sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (β = –5.89 mL/year) than in pre/perimenopausal women (β = –1.61 mL/year). Similar age–menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age–sex and age–menopause interactions were found for regional cortical and subcortical brain volumes.
Conclusion
Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.
Journal Article
Neuropsychiatric Symptoms as Predictors of Clinical Course in Neurodegeneration. A Longitudinal Study
: To study the extent to which neuropsychiatric symptoms (NPS) influence the cognitive and functional decline in frontotemporal degeneration (FTD) and Alzheimer's disease (AD).
: We assessed the progression of NPS and their influence on cognitive and functional progression in a group of FTD (
= 36) and AD patients (
= 47) at two different stages of the disease (2.5 years). A standardized scale was used to assess NPS-the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD)-which tracks different symptoms including depression, psychotic symptoms, as well as sleep and conduct problems. In addition, in a subsample of patients (AD
= 14 and FTD
= 14), we analyzed another group of NPS by using the Neuropsychiatric Inventory (NPI). Cognitive declines were tracked by using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), while functionality was tracked by using the Lawton scale and the Barthel Index.
: The presence of NPS impacts cognitive and functional decline in both groups of patients 2.5 years after disease onset. However, we observed a dissociable profile of the affectation of NPS in each group. In the AD group, results indicate that the progression of depressive symptoms and sleep problems predict cognitive and functional decline. In contrast, the progression of a mixed group of NPS, including conduct problems and delusions, predicts cognitive and functional decline in FTD.
: The presence of NPS has a critical impact on the prediction of cognitive decline in FTD and AD patients after 2.5 years of disease progression. Our results demonstrate the importance of assessing different types of NPS in neurodegenerative disorders which, in turn, predict disease progression. Future studies should assess the role of NPS in predicting different neurocognitive pathways and in neurodegeneration.
Journal Article
The effects of trazodone on human cognition: a systematic review
Trazodone is a widely used antidepressant that is also useful in the control of agitation and insomnia in Alzheimer's disease. This drug is now recognized as having a new mechanism of action, an effect on the unfolded protein response (UPR) pathway, restoring protein translation and slowing neurodegenerative progression in mice. This mechanism may have a role in dementia-modifying treatment. To explore the effects of trazodone on human cognition and to search for clinical evidence of its putative benefits in human neurodegenerative diseases, a systematic review was conducted for studies that evaluated the effect of a minimum dose of 25 mg of trazodone daily, for at least 1 week, on cognition in adult humans. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases, yielding a total of 16 studies after selection. Overall, seven studies showed no effect of trazodone on cognition, five showed a beneficial effect by improving or reducing cognitive decline, and four evidenced impaired cognitive function. Our analysis highlights the possibility of a dose-independent dual effect of trazodone on human cognition, with acute utilization associated with impaired cognitive function and long-term use with preventing cognitive deterioration. There was no clinical evidence that trazodone could be used as a specific treatment of neurodegenerative diseases. Future studies should explore the role of trazodone in the UPR pathway and the implications in neurodegenerative diseases in humans.
Journal Article
Memory activity book : engaging ways to stimulate the brain, for people living with memory loss or dementia
More than 70 brain-stimulating activities for people with memory loss or dementia, including Alzheimer's disease. Physical and mental activities along with social interaction may help maintain your brain health and slow the progress of memory loss and dementia, including Alzheimer's disease. They can also provide a meaningful way to connect. This book is packed with fun and creative ideas, from nature walks, gardening, and exercise to arts, crafts, puzzles, and games. Each activity includes step-by-step instructions, the specific benefits, and ways to adapt the activity for different abilities. Designed for people with memory loss or dementia along with their family, friends, and caregivers, AARP's Memory Activity Book is a valuable resource for everyone touched by these conditions.
Book
Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial
An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.
To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).
Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.
A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.
The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.
Controlled-Trials.com ISRCTN94410159.
Journal Article
Brain fitness : the easy way of keeping your mind sharp through qigong movements
The author shares her expertise in tai chi, qigong, and medicine, emphasizing how tai chi and qigong aid in memory, emotional balance, and lifelong learning. This book features an illustrated manual detailing tai chi and qigong exercises to prevent brain aging; and concise, accessible guidance in combining elements of eastern and western medicine to form a new vision of brain health.--Publisher.
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