scholarly journals Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

2020 ◽  
Vol 40 (12) ◽  
pp. 2475-2490 ◽  
Author(s):  
Ben Schager ◽  
Craig E Brown
Keyword(s):  
Visual Cortex ◽  
White Matter ◽  
Regional Differences ◽  
Grey Matter ◽  
Anterior Cerebral Artery ◽  
Cerebral Arteries ◽  
Brain Regions ◽  
Aging Brain ◽  
Age Related ◽  
Vessel Width

Vessel loss in the aging brain is commonly reported, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we imaged and quantified vessel length, tortuosity and width in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical grey matter regions, while some regions (visual cortex, amygdala, thalamus) showed no decline with aging. Regions supplied by the anterior cerebral artery were more vulnerable to loss than those supplied by middle or posterior cerebral arteries. Vessel width and tortuosity generally increased with age but neither reliably predicted regional vessel loss. Since capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning, we hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. These findings indicate that age-related vessel loss is region specific and can be explained, at least partially, by regional susceptibilities to capillary plugging.

scholarly journals Age differentiation within grey matter, white matter and between memory and white matter in an adult lifespan cohort

2017 ◽  
Author(s):  
Susanne M. M. de Mooij ◽  
Richard N. A. Henson ◽  
Lourens J. Waldorp ◽  
Cam-CAN ◽  
Rogier A. Kievit
Keyword(s):  
White Matter ◽  
Cognitive Functions ◽  
Structural Equation ◽  
Grey Matter ◽  
Fluid Intelligence ◽  
Cognitive Factors ◽  
Equation Modeling ◽  
Grey Matter Volume ◽  
Adult Lifespan ◽  
Age Related

AbstractIt is well-established that brain structures and cognitive functions change across the lifespan. A longstanding hypothesis called age differentiation additionally posits that the relations between cognitive functions also change with age. To date however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multi-group Structural Equation Modeling and SEM Trees to study differences within and between brain and cognition across the adult lifespan (18-88 years) in a large (N>646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of grey-matter volume (from T1- and T2-weighted MRI) and white-matter organisation (fractional anisotropy from Diffusion-weighted MRI), we found evidence for differentiation of grey and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation between fluid intelligence, language and memory, suggesting a relatively stable covariance pattern between cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.Significance statementThe theory of age differentiation posits age-related changes in the relationships between cognitive domains, either weakening (differentiation) or strengthening (de-differentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult lifespan sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change between cognitive factors of fluid intelligence, language and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.

scholarly journals White Matter Microstructure Predicts Focal and Broad Functional Brain Dedifferentiation in Normal Aging

2020 ◽  
Vol 32 (8) ◽  
pp. 1536-1549
Author(s):  
Jenny R. Rieck ◽  
Karen M. Rodrigue ◽  
Denise C. Park ◽  
Kristen M. Kennedy
Keyword(s):  
Visual Cortex ◽  
White Matter ◽  
Visual Processing ◽  
Brain Activity ◽  
Normal Aging ◽  
Important Variable ◽  
Functional Selectivity ◽  
Functional Responses ◽  
Age Related ◽  
Function Relationship

Ventral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed “dedifferentiation.” The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20–89 years, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as fMRI to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure–function relationship became weaker with age and was no longer significant after the age of 70 years. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.

scholarly journals Tau seeding activity anticipates phospho-tau pathology in Alzheimer’s disease

2018 ◽  
Author(s):  
Sarah K. Kaufman ◽  
Kelly Del Tredici ◽  
Talitha L. Thomas ◽  
Heiko Braak ◽  
Marc I. Diamond
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Cortex ◽  
Brain Regions ◽  
Tau Pathology ◽  
Age Related ◽  
Important Addition ◽  
Disease Stages ◽  
Relationship Of ◽  
The Relationship

AbstractAlzheimer’s disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological “seeds” may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/EC). The relationship of tau seeding activity, phospho-tau pathology, and progression of neurodegeneration remains obscure. Consequently, we employed an established cellular biosensor assay to quantify tau seeding activity in fixed human tissue, in parallel with AT8 phospho-tau staining of immediately adjacent sections. We studied four brain regions from each of n=247 individuals across a range of disease stages. We detected the earliest and most robust seeding activity in the TRE/EC. The LC did not uniformly exhibit seeding activity until later NFT stages. We also detected seeding activity in the first temporal gyrus and visual cortex at stages before NFTs and/or AT8-immunopositivity were detectable. AD and putative PART cases exhibited similar patterns of seeding activity that anticipated histopathology across all NFT stages. Our findings are consistent with the prion model and suggest that pathological seeding activity begins in the TRE/EC rather than in the LC, and may offer an important addition to classical histopathology.

Abstract MP057: Subclinical Cerebrovascular Disease is Associated with Worsening Gait and Balance in an Elderly Multi-Ethnic Population: The Northern Manhattan Study (NOMAS)

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Joshua Z Willey ◽  
Yeseon Park Moon ◽  
Janet DeRosa ◽  
Erin Kulick ◽  
Sandino Cespedes ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebrovascular Disease ◽  
White Matter Hyperintensities ◽  
Physical Aging ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
The Elderly ◽  
Brain Regions ◽  
Periventricular White Matter ◽  
Age Related

Introduction: Age-related decline in gait and balance is a contributor to morbidity in the elderly. Subclinical cerebrovascular disease, seen on magnetic resonance imaging (MRI) as white matter hyperintensities (WMH) and silent brain infarcts (SBI), is associated with impaired mobility. Less is known about the association of WMH in specific brain regions and mobility impairment. We hypothesized that anterior WMH volume would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale associated with falls and mortality in the elderly. Methods: Participants in the Northern Manhattan Study MRI cohort had the SPPB measured a median of 5 years after enrollment. The SPPB has three domains with a maximum total score of 12: gait speed, chair stands, standing balance. Volumetric distributions for WMH volume across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter) were determined separately for each hemisphere by combining bimodal image intensity distribution and atlas based methods. Multi-variable linear regression was performed to examine the association between SBI and total and regional (frontal, parietal, occipital, temporal, anterior, posterior, and brainstem) head size-corrected WMH volumes, with the total SPPB score; models were adjusted for cardiovascular disease risk factors, osteo-arthritis, and grip strength. Results: Among 668 stroke-free participants with the SPPB available, mean age at the time of assessment was 74 ±9 years, 37% were male and 70% Hispanic; the mean SPPB score was 8.2 ± 2.9, interquartile range 7-10. Mean total WMHV was 0.55±0.75cc, mean anterior WMH volume 0.18±0.24cc, and 12% of participants had SBI. In multi-variable models, total WMHV was associated with a lower SPPB (beta = -0.3 per SD of logWMH, p=0.004), while SBI was not (beta= -0.12, p=0.7). For regional WMH volumes, only greater anterior periventricular WMHV was associated with SPPB (beta= -0.29 per SD, p=0.009). Conclusions: White matter hyperintensities, especially in the anterior cerebral regions, are associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical aging in the elderly.

scholarly journals A Serpiginous Pericallosal Anterior Cerebral Artery

2018 ◽  
Vol 7 (6) ◽  
pp. 323-326
Author(s):  
Mohamad Ezzeldin ◽  
Eslam W. Youssef ◽  
Ali Sultan-Qurraie ◽  
Eugene Lin ◽  
Osama O. Zaidat
Keyword(s):  
White Matter ◽  
Clinical Significance ◽  
Congenital Malformation ◽  
Cerebral Artery ◽  
Anterior Cerebral Artery ◽  
Pediatric Population ◽  
Cerebral Arteries ◽  
Elastin Degradation ◽  
Intracranial Arteries ◽  
Anterior Posterior

The anterior cerebral artery (ACA) is a unique artery with many important variations with substantial clinical significance. Tortuous intracranial arteries usually occur in basilar, communicating, anterior, posterior cerebral arteries and in the white matter arterioles. This could happen for many reasons including but not limited to ageing, hypertension, patients with Moyamoya disease, congenital malformation, or increased flow associated with elastin degradation. While dolichoectasia of the ACA has been described even in children, to our knowledge, a serpiginous ACA without ectasia has not been reported, especially in the pediatric population.

scholarly journals Functional and structural correlates of the aging brain: Relating visual cortex (V1) gamma band responses to age‐related structural change

2011 ◽  
Vol 33 (9) ◽  
pp. 2035-2046 ◽  
Author(s):  
William Gaetz ◽  
Timothy P.L. Roberts ◽  
Krish D. Singh ◽  
Suresh D. Muthukumaraswamy
Keyword(s):  
Visual Cortex ◽  
Structural Change ◽  
Gamma Band ◽  
Aging Brain ◽  
Age Related

scholarly journals Age-related declines in neural distinctiveness correlate across brain areas and result from both decreased reliability and increased confusability

2021 ◽  
Author(s):  
Molly Simmonite ◽  
Thad A Polk
Keyword(s):  
Neural Activity ◽  
Healthy Aging ◽  
Brain Regions ◽  
Aging Brain ◽  
Activation Patterns ◽  
Neural Representations ◽  
Age Related ◽  
Behavioural Performance ◽  
The Difference ◽  
The Brain

According to the neural dedifferentiation hypothesis, age-related reductions in the distinctiveness of neural representations contribute to sensory, cognitive, and motor declines associated with aging: neural activity associated with different stimulus categories becomes more confusable with age and behavioural performance suffers as a result. Initial studies investigated age-related dedifferentiation in the visual cortex, but subsequent research has revealed declines in other brain regions, suggesting that dedifferentiation may be a general feature of the aging brain. In the present study, we used functional magnetic resonance imaging to investigate age-related dedifferentiation in the visual, auditory, and motor cortices. Participants were 58 young adults and 79 older adults. The similarity of activation patterns across different blocks of the same condition was calculated (within-condition correlation, a measure of reliability) as was the similarity of activation patterns elicited by different conditions (between-category correlations, a measure of confusability). Neural distinctiveness was defined as the difference between the mean within- and between-condition similarity. We found age-related reductions in neural distinctiveness in the visual, auditory, and motor cortices, which were driven by both decreases in within-category similarity and increases in between-category similarity. There were significant positive cross-region correlations between neural distinctiveness in different regions. These correlations were driven by within-category similarities, a finding that indicates that declines in the reliability of neural activity appear to occur in tandem across the brain. These findings suggest that the changes in neural distinctiveness that occur in healthy aging result from changes in both the reliability and confusability of patterns of neural activity.

scholarly journals White matter microstructure predicts focal and broad functional brain dedifferentiation in normal aging

2019 ◽  
Author(s):  
Jenny R. Rieck ◽  
Karen M. Rodrigue ◽  
Denise C. Park ◽  
Kristen M. Kennedy
Keyword(s):  
Visual Cortex ◽  
White Matter ◽  
Visual Processing ◽  
Brain Activity ◽  
Normal Aging ◽  
Important Variable ◽  
Functional Selectivity ◽  
Functional Responses ◽  
Age Related ◽  
Function Relationship

AbstractVentral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed “dedifferentiation”. The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20-89, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as functional magnetic resonance imaging to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure-function relationship became weaker with age and was no longer significant after age 70. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.

scholarly journals Modelling the Anatomical Distribution of Neurological Events in COVID-19 Patients: A Systematic Review

2020 ◽  
Author(s):  
Nicholas Parsons ◽  
Athanasia Outsikas ◽  
Annie Parish ◽  
Rebecca Clohesy ◽  
Nilam Thakkar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Spatial Distribution ◽  
White Matter ◽  
Diffusion Model ◽  
Grey Matter ◽  
Brain Regions ◽  
Neurological Symptoms ◽  
Linear Diffusion ◽  
Spread Model ◽  
Network Diffusion

SummaryBackgroundNeuropathology caused by the coronavirus disease 2019 (COVID-19) has been reported across several studies. The characterisation of the spatial distribution of these pathology remains critical to assess long and short-term neurological sequelae of COVID-19. To this end, Mathematical models can be used to characterise the location and aetiologies underlying COVID-19-related neuropathology.MethodWe performed a systematic review of the literature to quantify the locations of small neurological events identified with magnetic resonance imaging (MRI) among COVID-19 patients. Neurological events were localised into the Desikan-Killiany grey and white matter atlases. A mathematical network diffusion model was then used to test whether the spatial distribution of neurological events could be explained via a linear spread through the structural connectome of the brain.FindingsWe identified 35 articles consisting of 123 patients that assessed the spatial distribution of small neurological events among COVID-19 patients. Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds. White matter events were observed within 14 of 42 white matter bundles from the IIT atlas. The highest proportions (26%) of events were observed within the bilateral corticospinal tracts. The splenium and middle of the corpus callosum were affected in 14% and 9% of the cases respectively. Grey matter events were spatially distributed in the 41 brain regions within the Desikan-Killiany atlas. The highest proportions (∼10%) of the events were observed in areas including the bilateral superior temporal, precentral, and lateral occipital cortices. Sub-cortical events were most frequently identified in the Pallidum. The application of a mathematical network diffusion model suggested that the spatial pattern of the small neurological events in COVID-19 can be modelled with a linear diffusion of spread from epicentres in the bilateral cerebellum and basal ganglia (Pearson’s r=0.41, p<0.001, corrected).InterpretationTo our knowledge, this is the first study to systematically characterise the spatial distribution of small neurological events in COVID-19 patients and test whether the spatial distribution of these events can be explained by a linear diffusion spread model. The location of neurological events is consistent with commonly identified neurological symptoms including alterations in conscious state among COVID-19 patients that require brain imaging. Given the prevalence and severity of these manifestations, clinicians should carefully monitor neurological symptoms within COVID-19 patients and their potential long-term sequelae.

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