2,082 research outputs found
Neuroimaging Biomarkers of Caloric Restriction on Brain Metabolic and Vascular Functions
Purpose of Review
Non-invasive neuroimaging methods have been developed as powerful tools for identifying in vivo brain functions for studies in humans and animals. Here, we review the imaging biomarkers that are being used to determine the changes within brain metabolic and vascular functions induced by caloric restriction (CR) and their potential usefulness for future studies with dietary interventions in humans.
Recent Findings
CR causes an early shift in brain metabolism of glucose to ketone bodies and enhances ATP production, neuronal activity, and cerebral blood flow (CBF). With age, CR preserves mitochondrial activity, neurotransmission, CBF, and spatial memory. CR also reduces anxiety in aging mice. Neuroimaging studies in humans show that CR restores abnormal brain activity in the amygdala of women with obesity and enhances brain connectivity in old adults.
Summary
Neuroimaging methods have excellent translational values and can be widely applied in future studies to identify dietary effects on brain functions in humans
Multimodal MRI Neuroimaging Biomarkers for Cognitive Normal Adults, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease
Multimodal magnetic resonance imaging (MRI) techniques have been developed to noninvasively measure structural, metabolic, hemodynamic and functional changes of the brain. These advantages have made MRI an important tool to investigate neurodegenerative disorders, including diagnosis, disease progression monitoring, and treatment efficacy evaluation. This paper discusses recent findings of the multimodal MRI in the context of surrogate biomarkers for identifying the risk for AD in normal cognitive (NC) adults, brain anatomical and functional alterations in amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) patients. Further developments of these techniques and the establishment of promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and AD in their early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials
Neuroimaging in Dementia
Dementia is a common illness with an incidence that is rising as the aged population increases. There are a number of neurodegenerative diseases that cause dementia, including Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia, which is subdivided into the behavioral variant, the semantic variant, and nonfluent variant. Numerous other neurodegenerative illnesses have an associated dementia, including corticobasal degeneration, Creutzfeldt–Jakob disease, Huntington’s disease, progressive supranuclear palsy, multiple system atrophy, Parkinson’s disease dementia, and amyotrophic lateral sclerosis. Vascular dementia and AIDS dementia are secondary dementias. Diagnostic criteria have relied on a constellation of symptoms, but the definite diagnosis remains a pathologic one. As treatments become available and target specific molecular abnormalities, differentiating amongst the various primary dementias early on becomes essential. The role of imaging in dementia has traditionally been directed at ruling out treatable and reversible etiologies and not to use imaging to better understand the pathophysiology of the different dementias. Different brain imaging techniques allow the examination of the structure, biochemistry, metabolic state, and functional capacity of the brain. All of the major neurodegenerative disorders have relatively specific imaging findings that can be identified. New imaging techniques carry the hope of revolutionizing the diagnosis of neurodegenerative disease so as to obtain a complete molecular, structural, and metabolic characterization, which could be used to improve diagnosis and to stage each patient and follow disease progression and response to treatment. Structural and functional imaging modalities contribute to the diagnosis and understanding of the different dementias
Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment
Alzheimer’s disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adults with aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impaired thalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs
Cardiovascular health and brain aging : a population-based MRI study
Deterioration of brain structure and cognitive function occurs as individuals reach advanced
age. The former can be observed through various markers of cerebral small vessel disease on
magnetic resonance imaging (MRI) scans and the later can be assessed by neuropsychological
tests and clinical examinations. In addition, maintaining a favorable cardiovascular health
(CVH) status may contribute to delaying brain aging. Having a higher cognitive reserve (CR)
capacity may contribute to preserving cognitive function even in the presence of brain damage.
In this thesis, we aimed to examine the progression and interrelationships of MRI markers of
structural brain aging and the association between the progression of these markers and
cognitive decline. Furthermore, we aimed to investigate whether maintaining a favorable CVH
status would be related to a slower deterioration of brain structure and whether having a higher
CR capacity would be associated with a lower risk of cognitive deterioration and death. Data
were derived from the population-based Swedish National study on Aging and Care in
Kungsholmen from 2001–2004 to 2016–2019 and the MRI sub-study from 2001–2003 to
2007–2010.
Study I: This six-year follow-up study showed that the progression rate of cerebral small
vessel disease markers including expansion rates of white matter hyperintensities (WMHs) and
lateral ventricles, incidence of lacunes, and shrinkage rate of gray matter volume, but not the
progression rate of perivascular spaces (PVSs), steadily increased with aging (P < 0.05). The
progression rate of regional WMHs was faster in males than in females and in people without a
university degree than those with a degree (P < 0.05). In addition, a higher load of
microvascular lesions (i.e., WMHs, PVSs, and lacunes) at baseline was related to faster
progression of both microvascular lesions (WMHs and lacunes) and gray matter atrophy (P <
0.05).
Study II: This follow-up study showed that a greater burden of WMHs at baseline was
associated with a faster decline in executive function, letter fluency, perceptual speed, and
global cognition over 15 years (P < 0.05), but not in episodic or semantic memory. The faster
deterioration in category fluency was linked to greater periventricular WMHs at baseline only
in people carrying the APOE-ε4 allele (multivariable-adjusted β-coefficients and 95%
confidence interval [CI]: -0.018, -0.031– -0.004). Accelerated decline in perceptual speed over
15 years was linked to a faster increase in deep and periventricular WMHs during the first six
years, and accelerated decline in executive function and global cognition was linked to a faster
increase in deep WMHs during the first six years (P < 0.05).
Study III: This six-year follow-up study showed that compared to the unfavorable global CVH
profile, the intermediate-to-favorable profiles were associated with a slower accumulation of
WMHs (multivariable-adjusted β-coefficients and 95% CI: -0.019, -0.035– -0.002 and -0.018, -
0.034– -0.001, respectively). Intermediate-to-favorable biological CVH profiles were
associated with a slower WMH increase among people aged 60–72 years, but not in those aged
78 years and above. Furthermore, a higher metabolic genetic risk was linked to a faster
accumulation of WMHs in people with intermediate-to-favorable global or behavioral CVH
profiles, but not in those with favorable CVH profiles (P for both interactions = 0.001).
Study IV: This 15-year follow-up study revealed that a higher composite CR score, which was
estimated from early-life education, midlife work complexity, late-life leisure activities, and
late-life social network, was associated with a reduced risk of transition from normal cognition
to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio and 95%
CI: 0.78, 0.72–0.85) and death (0.85, 0.79–0.93) and from CIND to death (0.82, 0.73–0.91), but
not from CIND to dementia neither from CIND to normal cognition (P > 0.05). The risk of
transitions from normal cognition to CIND or death did not change after controlling for brain
aging markers, while the risk of transition from CIND to death became not significant.
Furthermore, a higher CR score was associated with a lower risk of transition from CIND to
death among people aged 60–72 years (0.65, 0.54–0.77) while not among those aged 78 years
and above (0.87, 0.75–1.01) (P for interaction = 0.010).
Conclusions: First, the deterioration of brain structure accelerates with advancing age. Cerebral
microvascular lesions are associated with accelerated brain atrophy. Second, WMHs are linked
to an accelerated decline in multiple cognitive domains except memory. A faster accumulation
of WMHs in deep brain regions is associated with an accelerated decline in perceptual speed
and executive function. Third, having a favorable CVH profile is associated with a slower
progression of structural brain aging attributable to metabolic genetic risk. Finally, having a
greater CR capacity might play a crucial role in preserving cognitive health and reducing
mortality rate in the prodromal phase of dementia, independent of brain aging markers. The
association between higher CR capacity and lower likelihood of transition from CIND to death
exists particularly among people in the early stage of older adulthood
Acute and Chronic Effects of Hypobaric Exposure upon the Brain
Exposure to the hypobaric environment presents numerous physiological challenges to both aviators/pilots, mountain climbers and astronauts. Decompression sickness (DCS) is one of the most commonly experienced maladies and may present variably in protean fashion from mild symptoms such as the bends to severe neurological or pulmonary (i.e. chokes) symptomatology. Furthermore, exposure to extreme non-hypoxic hypobaric environments such as those experienced by our U-2 pilots, irrespective of clinical history of decompression sickness, incites development of white matter hyperintensity lesions that are diffuse in nature. Additionally, non-hypoxic hypobaric exposure also impacts white matter integrity independent of presence of white matter hyperintensities as measured by fractional anisotropy. Functionally, this translated into subtle but significantly lower neurocognitive test performance in U-2 pilots exposed to extreme non-hypoxic hypobaric conditions when compared to pilots without repeated exposure and correlated with degree of white matter lesion burden. In this chapter, we discuss results of our U-2 pilot studies along with published research on high-altitude climbers. We also review ongoing and future directional research and discuss operational implications due to our findings of non-hypoxic hypobaric exposure. Lastly, we examine the incidence of DCS in our astronaut population as well as the risks of performing extravehicular activity (EVA)
The influence of body fat distribution on white matter integrity
Objective: Obesity has become a great health problem and increases the risk for cardiovascular and metabolic diseases as well as for cognitive impairments including brain alterations in gray and white matter structure and function. The differentiation of adipose tissue in visceral adipose tissue and subcutaneous adipose tissue was found to be greatly relevant due to its different composition and consequent potential for metabolic complications. Hence, the objective of this study was to investigate the relationship between body fat distribution, especially visceral and subcutaneous adipose tissue, and white matter integrity.
Methods: Diffusion tensor imaging (DTI) of the brain and whole body magnetic resonance imaging were performed of 48 healthy young to middle-aged lean, overweight and obese participants. The collected data included participant’s sex, age, body mass index, total body volume, volume of total, subcutaneous and visceral adipose tissue, total intracranial volume and DTI data of the brain. By using a region-of-interest-based approach, the DTI parameters fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were analyzed and correlated with the body mass index, total adipose tissue, subcutaneous and visceral adipose tissue, controlling for age, sex, total intracranial volume and BMI.
Results: We found significant positive correlations between visceral adipose tissue and mean diffusivity and radial diffusivity values in the hippocampal part of the left cingulum (p < 0.005, corrected for number of tested regions) and marginally significant positive correlations in the forceps major and hippocampal part of the right cingulum (p < 0.05). Subcutaneous and total adipose tissue did not show significant correlations with DTI parameters.
Conclusion: Our DTI study contributed to the current knowledge of the relationship between visceral adipose tissue and white matter integrity. We conclude that increased visceral adipose tissue is associated with reduced white matter integrity in regions which are known to be important for emotional and cognitive functioning. Therefore we suggest that increased visceral adipose tissue may increase the risk for emotional and cognitive impairment. Still further longitudinal studies may determine causal impact of visceral adipose tissue and its clinical relevance
White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI
Frontotemporal dementia (FTD) and Alzheimer's disease are sometimes difficult to differentiate clinically because of overlapping symptoms. Using diffusion tensor imaging (DTI) measurements of fractional anisotropy (FA) can be useful in distinguishing the different patterns of white matter degradation between the two dementias. In this study, we performed MRI scans in a 4 Tesla MRI machine including T1-weighted structural images and diffusion tensor images in 18 patients with FTD, 18 patients with Alzheimer's disease and 19 cognitively normal (CN) controls. FA was measured selectively in specific fibre tracts (including corpus callosum, cingulum, uncinate and corticospinal tracts) as well as globally in a voxel-by-voxel analysis. Patients with FTD were associated with reductions of FA in frontal and temporal regions including the anterior corpus callosum (P < 0.001), bilateral anterior (left P < 0.001; right P = 0.005), descending (left P < 0.001; right P = 0.003) cingulum tracts, and uncinate tracts (left P < 0.001; right P = 0.005), compared to controls. Patients with Alzheimer's disease were associated with reductions of FA in parietal, temporal and frontal regions including the left anterior (P = 0.003) and posterior (P = 0.002) cingulum tracts, bilateral descending cingulum tracts (P < 0.001) and left uncinate tracts (P < 0.001) compared to controls. When compared with Alzheimer's disease, FTD was associated with greater reductions of FA in frontal brain regions, whereas no region in Alzheimer's disease showed greater reductions of FA when compared to FTD. In conclusion, the regional patterns of anisotropy reduction in FTD and Alzheimer's disease compared to controls suggest a characteristic distribution of white matter degradation in each disease. Moreover, the white matter degradation seems to be more prominent in FTD than in Alzheimer's disease. Taken together, the results suggest that white matter degradation measured with DTI may improve the diagnostic differentiation between FTD and Alzheimer's disease
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