Blueprint for a Brain Health Clinic to Detect and Manage Early-Stage Cognitive Decline: A Consensus Exercise

Abstract Background The incidence of dementia and cognitive decline is increasing with no therapy or cure. One of the reasons treatment remains elusive is because there are various pathologies that contribute to age-related cognitive decline. Specifically, with Alzheimer’s disease, targeting to reduce amyloid beta plaques and phosphorylated tau aggregates in clinical trials has not yielded results to slow symptomology, suggesting a new approach is needed. Interestingly, exercise has been proposed as a potential therapeutic intervention to improve brain health and reduce the risk for dementia, however the benefits throughout aging are not well understood. Results To better understand the effects of exercise, we preformed transcriptional profiling on young (1–2 months) and midlife (12 months) C57BL/6 J (B6) male mice after 12 weeks of voluntary running. Data was compared to age-matched sedentary controls. Interestingly, the midlife running group naturally broke into two cohorts based on distance ran - either running a lot and more intensely (high runners) or running less and less intensely (low runners). Midlife high runners had lower LDL cholesterol as well as lower adiposity (%fat) compared to sedentary, than midlife low runners compared to sedentary suggesting more intense running lowered systemic markers of risk for age-related diseases including dementias. Differential gene analysis of transcriptional profiles generated from the cortex and hippocampus showed thousands of differentially expressed (DE) genes when comparing young runners to sedentary controls. However, only a few hundred genes were DE comparing either midlife high runners or midlife low runners to midlife sedentary controls. This indicates that, in our study, the effects of running are reduced through aging. Gene set enrichment analyses identified enrichment of genes involved in extracellular matrix (ECM), vascular remodeling and angiogenesis in young runners but not midlife runners. These genes are known to be expressed in multiple vascular-related cell types including astrocytes, endothelial cells, pericytes and smooth muscle cells. Conclusions Taken together these results suggest running may best serve as a preventative measure to reduce risk for cerebrovascular decline. Ultimately, this work shows that exercise may be more effective to prevent dementia if introduced at younger ages.

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An epigenetic predictor of death captures multi-modal measures of brain health

Molecular Psychiatry ◽

10.1038/s41380-019-0616-9 ◽

2019 ◽

Cited By ~ 6

Author(s):

Robert F. Hillary ◽

Anna J. Stevenson ◽

Simon R. Cox ◽

Daniel L. McCartney ◽

Sarah E. Harris ◽

...

Keyword(s):

Cognitive Decline ◽

Cognitive Ability ◽

Vascular Lesions ◽

Epigenetic Clock ◽

General Cognitive Ability ◽

Brain Health ◽

Standard Deviation Increase ◽

Brain White Matter ◽

Age Related ◽

Tentative Evidence

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10−16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = −0.11), lower age 73 general cognitive ability (β = −0.18), decreased brain volume (β = −0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

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GAIT SPEED AND CHILDHOOD-TO-MIDLIFE BRAIN HEALTH: RETHINKING GAIT

Innovation in Aging ◽

10.1093/geroni/igz038.3192 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S870-S870

Author(s):

Line Rasmussen ◽

Avshalom Caspi ◽

Terrie Moffitt ◽

Harvey J Cohen ◽

Miriam C Morey ◽

...

Keyword(s):

Cognitive Decline ◽

Gait Speed ◽

Functional Decline ◽

Multiple Organ ◽

Biological Aging ◽

Brain Health ◽

Organ Systems ◽

Physical Functions ◽

Physical Limitations ◽

Midlife Adults

Abstract Background: Gait speed is a well-known predictor of functional decline and mortality in older adults, but little is known about the origins of gait speed earlier in life. We tested the hypothesis that slow gait reflects accelerated biological aging already at midlife, as well as poor neurocognitive functioning in childhood and childhood-to-midlife cognitive decline. Methods: Prospective study of the population-representative Dunedin Study birth cohort (n=1,037), followed to age 45 (until April 2019). We measured age-45 gait speed in 904 (90.7%) participants and tested associations with key life course factors. Results: The mean (SD) gait speeds (m/s) were: usual: 1.30 (0.17); dual task: 1.16 (0.23); and maximum: 1.99 (0.29). Among midlife adults, those with more physical limitations (β -0.27; P<.001), poorer physical functions (β 0.24–0.36; all P<.001), accelerated biological aging across multiple organ systems (β -0.33), older facial appearance (β -0.25), smaller brain volume (β 0.15), more cortical thinning (β 0.09), smaller cortical surface area (β 0.13), and more white matter hyperintensities (β -0.09) had slower gait speed, all P<.05. Participants with lower IQ in childhood (β 0.34) and midlife (β 0.38) and who exhibited childhood-to-midlife cognitive decline (β 0.10) had slower gait speed at midlife, all P<.01. Adults with poorer neurocognitive function as early as age 3 had slower gait in midlife (β 0.26; P<.001). Conclusion: Adults’ gait speed is more than an indicator of geriatric functional status, it is also an index of midlife aging and lifelong brain health.

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Investigating whether vitamin B12 and folic acid supplementation slows cognitive decline

Impact ◽

10.21820/23987073.2018.3.82 ◽

2018 ◽

Vol 2018 (3) ◽

pp. 82-83

Author(s):

Timothy Chi-yui Kwok

Keyword(s):

Hong Kong ◽

Cognitive Decline ◽

Early Stage ◽

The Elderly ◽

Folic Acid Supplementation ◽

Vitamin B ◽

Ongoing Research ◽

University Of Oxford ◽

Mild Impairment ◽

And Function

Given the increase in average lifespans in countries around the world, diseases that afflict the elderly are a major focus for scientists. Uppermost among these is dementia, a broad term which includes many types of cognitive decline from mild impairment to severe conditions such as Alzheimer's disease. We lose brain volume and function as we age, and it is this atrophy of different parts of the brain that leads to loss of cognitive function. Although atrophy takes many different forms and thus results in a range of conditions, there are commonalities between each that might be targets for treatment. One area of research is the possibility of using large doses of B vitamins to lower levels of the amino acid homocysteine, which has been linked to many conditions including cardiovascular disease and dementia. This is the focus of Professor Timothy Kwok's ongoing research at the Chinese University of Hong Kong. Kwok is also a practising consultant geriatrician at the Prince of Wales Hospital in Hong Kong and has been inspired to pursue this field of inquiry by the need for simple and inexpensive treatments which could be made available to large numbers of elderly patients. He says: 'A trial at the University of Oxford showed that lowering homocysteine levels led to a significant reduction in the rate of brain atrophy. However, many questions remain unanswered and our current two-year trial will hopefully give further insights into the benefits or otherwise of vitamin B supplementation. If a causative link can be found between vitamin B supplementation and a slower rate of cognitive decline, this would be an inexpensive and safe way of treating people at the early stage of disease. In addition, these vitamins could potentially be given as a preventative treatment in older people who are not yet showing signs of cognitive impairment. As Kwok says: 'Dementia is a major cause of dependency in old age and has a big impact on the people affected, their families and scarce medical resources. If supplementation could prevent dementia in people with early symptoms, this simple intervention could make a huge difference to the quality of life of elderly people and reduce the burden of dementia on national health services.'

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Abstract P2-12-05: Neuropsychological assessment, neuroimaging, and tumor markers to explore cognitive decline in early stage breast cancer patients

10.1158/1538-7445.sabcs19-p2-12-05 ◽

2020 ◽

Author(s):

Claudia Panciroli ◽

Carles Biarnes ◽

Josep Puig ◽

Jose Anton Anton ◽

Vanesa Quiroga ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Decline ◽

Cancer Patients ◽

Tumor Markers ◽

Neuropsychological Assessment ◽

Early Stage ◽

Early Stage Breast Cancer ◽

Breast Cancer Patients

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DIABETES MELLITUS AND COGNITIVE DECLINE – PREVENTION SHOULD NOT BE DELAYED!

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2018.9 ◽

2018 ◽

pp. 1-3

Author(s):

A.J. Sinclair ◽

B. Vellas

Keyword(s):

Diabetes Mellitus ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Early Stage ◽

Neurodegenerative Dementia ◽

History Of ◽

Recent Addition

The recent addition of the Diabetes and Cognitive Decline section to JPAD marks a milestone in the history of this progressive journal as it recognises the important contribution that Diabetes makes to the aetiology of both vascular and neurodegenerative dementia syndromes (1-3). It has been observed that diabetes in the presence of hypertension leads to a more pronounced cognitive decline (4) and that at an early stage of cognitive decline (mild cognitive impairment ( MCI)), diabetes accelerates the progression of MCI to dementia (5).

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Effect of apolipoprotein E ε4 allele on the progression of cognitive decline in the early stage of Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions ◽

10.1002/trc2.12007 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Kazushi Suzuki ◽

Akihiro Hirakawa ◽

Ryoko Ihara ◽

Atsushi Iwata ◽

Kenji Ishii ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Early Stage ◽

Ε4 Allele

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Improving Dignity of Care in Community-Dwelling Elderly Patients with Cognitive Decline and Their Caregivers. The Role of Dignity Therapy

Behavioral Sciences ◽

10.3390/bs10120178 ◽

2020 ◽

Vol 10 (12) ◽

pp. 178

Author(s):

Heifa Ounalli ◽

David Mamo ◽

Ines Testoni ◽

Martino Belvederi Murri ◽

Rosangela Caruso ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Decline ◽

Early Stage ◽

Psychosocial Interventions ◽

The Elderly ◽

Community Dwelling ◽

Anticipatory Grief ◽

Dignity Therapy ◽

Existential Distress ◽

Age Related

Demographic changes have placed age-related mental health disorders at the forefront of public health challenges over the next three decades worldwide. Within the context of cognitive impairment and neurocognitive disorders among elderly people, the fragmentation of the self is associated with existential suffering, loss of meaning and dignity for the patient, as well as with a significant burden for the caregiver. Psychosocial interventions are part of a person-centered approach to cognitive impairment (including early stage dementia and dementia). Dignity therapy (DT) is a therapeutic intervention that has been shown to be effective in reducing existential distress, mood, and anxiety symptoms and improving dignity in persons with cancer and other terminal conditions in palliative care settings. The aims of this paper were: (i) To briefly summarize key issues and challenges related to care in gerontology considering specifically frail elderly/elderly with cognitive decline and their caregivers; and (ii) to provide a narrative review of the recent knowledge and evidence on DT in the elderly population with cognitive impairment. We searched the electronic data base (CINAHL, SCOPUS, PSycInfo, and PubMed studies) for studies regarding the application of DT in the elderly. Additionally, given the caregiver’s role as a custodian of diachronic unity of the cared-for and the need to help caregivers to cope with their own existential distress and anticipatory grief, we also propose a DT-dyadic approach addressing the needs of the family as a whole.

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