Gene L. Bowman

• ND MPH
• Clinical Trial Director; Instructor in Investigation and Neurology at Massachusetts General Hospital and Harvard University

Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synth...

Objectives: Nutritional metabolomics to objectively assess dietary intake in aging permit the opportunity to circumvent measurement errors that accompany subjective means of dietary assessment. At the same time, they may offer insights into mechanisms of action and metabolic disturbances that are actionable targets for modulation through diet in h...

Background Multiple pathophysiological processes have been described in Alzheimer’s disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alt...

The role of nutrition has been investigated for decades under the assumption of one‐size‐fits‐all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, def...

This chapter reviews body weight and composition, hydration, energy intake, and modifiers of food preference and summarizes nutrition literature associated with healthy brain, bone, and muscle ageing from a clinical and public health perspective. Certain nutrients are of particular importance in older adults where malnutrition and malabsorption are...

Background Nutrient biomarkers (NBs) may serve as more accurate and precise indicators of dietary intake, particularly in older adults who often have subtle episodic memory recall and digestive/microbiome issues that alter the nutritional substrate readily available to the brain. NBs also allow insight into modes of action and metabolic changes tha...

Importance Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, includ...

Background Neuropsychiatric symptoms (NPS) are common in older people, may precede cognitive decline, and are associated with worse long‐term prognosis. However, the underlying pathophysiology remains unclear. Therefore, our main objective was to examine systemic and central nervous system (CNS) protein signatures and regional brain volumetry patte...

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's d...

Neuropsychiatric symptoms (NPS) in older people worsen the patients’ and caregivers’ quality of life and are associated with cognitive decline. A better understanding of the biology underlying NPS may lead to novel ways for early detection and more targeted treatment. This study tested the hypothesis that NPS are associated with altered protein lev...

Neuropsychiatric symptoms (NPS) severely affect patients and their caregivers, and are associated with worse long‐term outcomes. This study tested the hypothesis that altered protein levels in blood plasma could serve as biomarkers of NPS; and that altered protein levels are associated with persisting NPS and cognitive decline over time. We perform...

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementi...

Background: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy). Objectives: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout...

Background Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical...

Although neuropsychiatric symptoms (NPS) are common and severely affect older people with cognitive decline, little is known about their underlying molecular mechanisms and relationships with Alzheimer’s disease (AD). The aim of this study was to identify and characterize cerebrospinal fluid (CSF) proteome alterations related to NPS. In a longitudi...

Background Blood levels of marine n‐3 PUFA (20:5; 22:6) are inversely associated with cerebral white matter lesion volume (WML), suggesting that n‐3 may offer one approach to reduce this major vascular contributor to cognitive impairment and dementia. This trial determined whether n‐3 slows WML progression and sustains white matter integrity over 3...

Background Blood‐brain barrier (BBB) breakdown and accummulation of Alzheimer disease (AD) pathology are risk factors for age‐related dementia. However, both require either lumbar puncture or advanced neuroimaging for detection that are not widely available. Less invasive ways to detect these risk factors early on could permit more targeted therapi...

Background Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical...

Introduction Human neurodevelopment is complete by the 4th decade of life at which point brain atrophy ensues with variable rate and regionality into old age. Literally all regions of the brain experience atrophy with older age, however the pattern and rate of atrophy can dictate the behavioral consequences (i.e., cognitive impairment, Alzheimer’s...

Background: Multiple pathophysiological processes have been described in Alzheimer’s disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood, however. We tested the hypothesis that cerebrospinal fluid (CSF) integrative multi-omics analysis hig...

Background The n‐3 PUFA may modulate risk for age‐related cognitive impairment through vascular mechanisms. MRI derived cerebral white matter hyperintensities (WMH) presumptively reflect small vessel disease and their accumulation increases risk for age‐related cognitive decline and dementia. Blood n‐3 PUFA are consistently associated with reduced...

BACKGROUND Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). Here, our objective was to determine systemic and central nervous system (CNS) inflammatory signatures associated with neuropsychiatric symptoms (NPS) in older subjects, and investigate their relationships w...

Objectives: Nutrients and their metabolites have interactive qualities that may be harnessed for prevention of cognitive decline. Simultaneous modulation of one-carbon, fatty acid and vitamin D metabolism (25-OH-D) may offer neuroprotection. We examined whether n-3 polyunsaturated fatty acids (n-3 PUFA), 25-OH-D, and homocysteine (HCy) formed into...

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitivel...

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soy...

The systems-level relationship between the proteomes of cerebrospinal fluid (CSF) and plasma has not been comprehensively described so far. Recently developed shotgun proteomic workflows allow for deeper characterization of the proteomes from body fluids in much larger sample size. We deployed state-of-the-art mass spectrometry-based proteomics in...

Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. Methods: The NRI inc...

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The...

Introduction: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. Methods: Cer...

Background: Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery wo...

https://deepblue.lib.umich.edu/bitstream/2027.42/153226/1/alzjjalz2018062866.pdf

Objectives: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical β-...

Background Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer’s disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve...

There are approximately 1,000 genes involved in odor recognition and 347 that code for functional receptors. This enables our distinguishing of approximately 4,000–10,000 distinct odorous ligands, a scientific discovery that earned a Nobel Prize in 2004.¹ The olfactory nerve (CN1) contains 6–10 million receptor cells whose ciliated dendrites and ce...

Background: In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarker...

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies....

Nestle perspective on research and development in brain health

https://deepblue.lib.umich.edu/bitstream/2027.42/152871/1/alzjjalz201506847.pdf

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between n...

We previously identified distinct nutrient biomarker patterns associated with both psychometric and neuroimaging indices of brain health in a cross‐sectional analysis of older adults. Those results propose that certain nutritional combinations influence global cognitive capacity, but also some relationships were more discrete and mapped to specific...

Introduction: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time a...

Background: Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and an...

Objective Omega 3 PUFAs may work on vascular pathology mediated cognitive decline, including brain white matter lesions and executive skills. We examined whether PUFAs are associated with cognitive domains (executive function and processing speeds) historically sensitive to the accumulation of white matter hyperintensities (WMH). Methods This coho...

Objectives: To elucidate the mechanism through which vitamin D is associated with decreased falls. Design: This was a convenience sample from a larger observational study examining correlations between vitamin D and 1) falls, 2) motor function, and 3) cognition (n=159). Setting: Falls data were collected via weekly on-line surveys completed in...

Purpose We previously identified three distinct nutrient biomar-ker patterns associated with both psychometric and neu-roimaging indices of brain health in a cross-sectional analysis. The objective of this study was to examine the relationship between the nutrient biomarker patterns and cognitive decline over 2 years. Methods Thirty biological mark...

Background. Blood-brain barrier (BBB) dysfunction may have a significant role in the pathogenesis of Alzheimer's disease (AD). Modifiable factors associated with BBB function may have therapeutic implication. This study tested the hypothesis that dyslipidemia is associated with BBB impairment in mild-to-moderate AD. Methods. Thirty-six subjects wit...

Background We previously identified three distinct nutrient biomarker patterns associated with both psychometric and neuroimaging indices in a cross‐sectional analysis. The objective of this study was to examine the relationship between the nutrient biomarker patterns and cognitive decline over 2 years. Methods Thirty biological markers of diet we...

This study examined the relation of micronutrient intake and cognitive function in elderly men. The analytic sample included 5625 community dwelling men age 65–100 (mean(sd) age 73(6) years) free of cognitive impairment (Modified Mini Mental (3MS)≥80). The Block food frequency questionnaire (FFQ), 3MS, Trail Making Test part B (TB), and medical his...

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future researc...

To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed t...

Clinical trials of single or few nutrients to slow the progression or delay the onset of Alzheimer's disease have been unsuccessful. One explanation may be related to more minimal effects that nutrients have in isolation. However, rigorous methods to define the ideal set of nutrients to inform this view have remained elusive. We applied a data driv...

There is great interest in the nutritional strategies for the prevention of age-related cognitive decline, yet the best methods for nutritional assessment in the populations at risk for dementia are still evolving. Our study objective was to examine the reliability and validity of the 2 common nutritional assessments (plasma nutrient biomarkers and...

Certain micronutrients are protective against cognitive decline. We examined whether there is any uniform pattern of circulating micronutrients cross–culturally that are associated with successful cognitive aging. For the U.S. sample, we used the stored serum/plasma of 115 participants, collected in Oregon, USA. The Okinawa sample consisted of 49 p...

Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was...

The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA....

Successful prevention and treatment of late-onset Alzheimer's disease (AD) is a high priority for industrialized societies where the incidence is growing rapidly. Much of the underlying biology leading to AD is unknown, and the more knowledge we gain the more we appreciate the complexities involved. Popular etiologic hypotheses have largely ignored...

To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD). Thirty-six patients (mean age 71 +/- 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 +/- 5) participated in a biomarker study involving clinical assessments, brain imaging...

Thesis (ND)--National University of Natural Medicine, Portland Or. Includes bibliographical references.