scholarly journals White matter hyperintensities are common in midlife and already associated with cognitive decline

2019 ◽  
Author(s):  
Tracy d’Arbeloff ◽  
Maxwell L. Elliott ◽  
Annchen R. Knodt ◽  
Tracy R. Melzer ◽  
Ross Keenan ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Clinical Symptoms ◽  
Early Prevention ◽  
Dementia Prevention ◽  
Increased Risk ◽  
Prevention Trials ◽  
Intervention Trials ◽  
The Brain

AbstractWhite matter hyperintensities (WMHs) proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, WMHs have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging WMHs begin to relate to cognition and if they may be a viable target for early prevention. In a population-representative birth cohort of 843 45-year-olds we measured WMHs using T2-weighted MRI, and we assessed cognitive decline from childhood to midlife. We found that WMHs were common at age 45 and that WMH volume was modestly associated with both lower childhood (ß=-0.08, p=0.013) and adult IQ (ß=-0.15, p<0.001). Moreover, WMH volume was associated with greater cognitive decline from childhood to midlife (ß=-0.09, p<0.001). Our results demonstrate that a link between WMHs and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, WMHs may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

scholarly journals White matter hyperintensities are common in midlife and already associated with cognitive decline

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Tracy d’Arbeloff ◽  
Maxwell L Elliott ◽  
Annchen R Knodt ◽  
Tracy R Melzer ◽  
Ross Keenan ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Dementia Prevention ◽  
Increased Risk ◽  
Weighted Magnetic Resonance Imaging ◽  
Intervention Trials ◽  
The Brain

Abstract White matter hyperintensities proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, white matter hyperintensities have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging white matter hyperintensities begin to relate to cognition and if they may be a viable target for early prevention. In the Dunedin Study, a population-representative cohort followed since birth, we measured white matter hyperintensities in 843 45-year-old participants using T2-weighted magnetic resonance imaging and we assessed cognitive decline from childhood to midlife. We found that white matter hyperintensities were common at age 45 and that white matter hyperintensity volume was modestly associated with both lower childhood (ß = −0.08, P = 0.013) and adult IQ (ß=−0.15, P &lt; 0.001). Moreover, white matter hyperintensity volume was associated with greater cognitive decline from childhood to midlife (ß=−0.09, P &lt; 0.001). Our results demonstrate that a link between white matter hyperintensities and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, white matter hyperintensities may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

083 Response to immunosuppressive therapy in cerebral amyloid angiopathy-related inflammation

2018 ◽  
Vol 89 (6) ◽  
pp. A33.3-A34
Author(s):  
Jasmin Tilling ◽  
Benjamin Trewin ◽  
Stanley Levy
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Cerebral Amyloid Angiopathy ◽  
White Matter Hyperintensities ◽  
Neurological Deficits ◽  
Amyloid Angiopathy ◽  
Dramatic Improvement ◽  
Age Related ◽  
Cerebral Amyloid ◽  
The Brain

IntroductionCerebral amyloid angiopathy (CAA) is a common age-related condition characterised by amyloid beta-peptide deposition affecting the medium sized cortical and leptomeningeal arteries, arterioles and capillaries. CAA-related Inflammation (CAA-I) is an increasingly recognised variant of CAA, which is thought to be due to perivascular auto-inflammation in response to amyloid deposition. We describe the clinical course of two cases of probable CAA-I.CasesA 71 year old man presented with new-onset seizures, headaches and subacute cognitive decline. MRI of the brain demonstrated confluent subcortical T2 white matter hyperintensities and cerebral oedema, with predominantly superimposed widespread cortico-subcortical micro-haemorrhages, in keeping with the diagnosis of CAA-I. A course of immunosuppresive therapy was commenced with five days of intravenous methylprednisolone, resulting in marked radiological and clinical improvement within two weeks.A 76 year old female presented with subacute cognitive dysfunction and apraxia, and transient left-sided weakness. MRI scan of the brain initially demonstrated a right temporo-occipital infarct, leading to primary treatment for stroke, but subsequently evolved to reveal diffuse multi-lobar T2 white matter hyperintensities with leptomeningeal involvement. A provisional diagnosis of CAA-I was made and following a poor clinical response to a trial of corticosteroid therapy, treatment with intravenous cyclophosphamide was commenced.ConclusionThese cases emphasise the importance of CAA-I as part of the differential diagnosis in patients presenting with symptoms of subacute cognitive decline, seizures, headaches and focal neurological deficits, given the potential for dramatic improvement with readily accessible immunosuppressive therapies.

Clinicopathological investigation of the background of cognitive decline in elderly schizophrenia

2020 ◽  
pp. 1-7
Author(s):  
Ayako Miwa ◽  
Mitsuaki Hirano ◽  
Youta Torii ◽  
Hirotaka Sekiguchi ◽  
Chikako Habuchi ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Clinical Symptoms ◽  
Dementia Syndrome ◽  
Increased Risk ◽  
Neuropathological Diagnosis ◽  
Schizophrenic Patients ◽  
Β Amyloid ◽  
The Brain ◽  
Normal Controls

Abstract Objective: We have often observed dementia symptoms or severe neurocognitive decline in the long-term course of schizophrenia. While there are epidemiological reports that patients with schizophrenia are at an increased risk of developing dementia, there are also neuropathological reports that the prevalence of Alzheimer’s disease (AD) in schizophrenia is similar to that in normal controls. It is difficult to distinguish, based solely on the clinical symptoms, whether the remarkable dementia symptoms and cognitive decline seen in elderly schizophrenia are due to the course of the disease itself or a concomitant neurocognitive disease. Neuropathological observation is needed for discrimination. Methods: We conducted a neuropathological search on three cases of schizophrenia that developed cognitive decline or dementia symptoms after a long illness course of schizophrenia. The clinical symptoms of total disease course were confirmed retrospectively in the medical record. We have evaluated neuropathological diagnosis based on not only Hematoxylin–Eosin and Klüver–Barrera staining specimens but also immunohistochemical stained specimens including tau, β-amyloid, pTDP-43 and α-synuclein protein throughout clinicopathological conference with multiple neuropathologists and psychiatrists. Results: The three cases showed no significant pathological findings or preclinical degenerative findings, and poor findings consistent with symptoms of dementia were noted. Conclusion: Although the biological background of dementia symptoms in elderly schizophrenic patients is still unclear, regarding the brain capacity/cognitive reserve ability, preclinical neurodegeneration changes in combination with certain brain vulnerabilities due to schizophrenia itself are thought to induce dementia syndrome and severe cognitive decline.

scholarly journals Tai Chi Training Evokes Significant Changes in Brain White Matter Network in Older Women

Healthcare ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 57 ◽  
Author(s):  
Chunlin Yue ◽  
Liye Zou ◽  
Jian Mei ◽  
Damien Moore ◽  
Fabian Herold ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Tai Chi ◽  
Elderly Women ◽  
Diffusion Tensor ◽  
Brain White Matter ◽  
Increased Risk ◽  
Significant Difference ◽  
The Brain ◽  
Walking Group

Background: Cognitive decline is age relevant and it can start as early as middle age. The decline becomes more obvious among older adults, which is highly associated with increased risk of developing dementia (e.g., Alzheimer’s disease). White matter damage was found to be related to cognitive decline through aging. The purpose of the current study was to compare the effects of Tai Chi (TC) versus walking on the brain white matter network among Chinese elderly women. Methods: A cross-sectional study was conducted where 42 healthy elderly women were included. Tai Chi practitioners (20 females, average age: 62.9 ± 2.38 years, education level 9.05 ± 1.8 years) and the matched walking participants (22 females, average age: 63.27 ± 3.58 years, educational level: 8.86 ± 2.74 years) underwent resting-state functional magnetic resonance imaging (rsfMRI) scans. Diffusion tensor imaging (DTI) and graph theory were employed to study the data, construct the white matter matrix, and compare the brain network attributes between the two groups. Results: Results from graph-based analyses showed that the small-world attributes were higher for the TC group than for the walking group (p < 0.05, Cohen’s d = 1.534). Some effects were significant (p < 0.001) with very large effect sizes. Meanwhile, the aggregation coefficient and local efficiency attributes were also higher for the TC group than for the walking group (p > 0.05). However, no significant difference was found between the two groups in node attributes and edge analysis. Conclusion: Regular TC training is more conducive to optimize the brain functioning and networking of the elderly. The results of the current study help to identify the mechanisms underlying the cognitive protective effects of TC.

Abstract 221: Regional Vulnerability within White Matter tracts to White Matter Hyperintensities: a Diffusion Tensor Imaging Tractography Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Pauline Maillard ◽  
Sudha Seshadri ◽  
Alexa Beiser ◽  
Jayandra Himali ◽  
Charles DeCarli
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Fiber Tracts ◽  
Regional Vulnerability ◽  
Increased Risk ◽  
The Impact

Background: Characterizing the impact of cerebral white matter (WM) damage on age related cognitive decline is of growing interest. White matter hyperintensities (WMH) and reduced microstructural WM integrity, as expressed by diffusion tensor imaging (DTI), have been associated with increased risk of clinically cognitive decline in the elderly, but the regional vulnerability within certain WM tracts to WMH is not well understood. Characterizing the implication and interactions of microstructural integrity and WMH within specific WM tracts would further elucidate mechanisms of cognitive decline in normal aging. Methods: 410 cognitively normal individuals from the Offspring Framingham Heart Study, aged 72.5±7.5 ([54.2; 104.9]), received a comprehensive clinical evaluation and brain MRI including FLAIR and DTI sequences. WM tractography was performed from DTI using FSL tools, resulting in 27 fiber tracts maps for each subject. WMHs were detected on FLAIR scans using a standardized protocol and coregistered to the subject DTI space. The mean fractional anisotrophy (mFA) within each tract was computed. Superimposition of WMH masks onto fiber tracts maps was used to calculate the overlap ratio of WMH (WMHor) within each tract. For each tract, mFA was regressed against the age and tract size and resulting residuals related to WMHor using a linear regression model. Results: The highest rates of WMHor were found within the thalamic radiations (range: [0- 28%]) and the inferior longitudinal fasciculi ([0- 29%]). Lower mFA was independently associated with larger WMHor within almost all association and projection fibers (p values<0.05). Correcting for the overall WMH burden did not significantly alter the results. Discussion: Regional mean FA has been previously associated with the overall WMH burden. We extended this finding by showing that, independently of the overall WM injury, microstructural WM integrity was associated with WMH within specific fiber tracts. Further investigations are needed to detangle the impact of specific tract disruption from that of more generalized subtle WM injury on cognitive decline.

Predictors for cognitive decline in patients with confluent white matter hyperintensities

2012 ◽  
Vol 8 ◽  
pp. S96-S103 ◽  
Author(s):  
Vincent Mok ◽  
Yunyun Xiong ◽  
Kelvin K. Wong ◽  
Adrian Wong ◽  
Reinhold Schmidt ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities

scholarly journals Role of white matter hyperintensities, hemoglobin and vitamin B‐12 on cognitive decline: Two‐year follow‐up data from the Tata Longitudinal Study of Ageing (TLSA)

2020 ◽  
Vol 16 (S6) ◽  
Author(s):  
Aditi Balakrishnan ◽  
Vivek Tiwari ◽  
M.L. Abhishek ◽  
Naren P. Rao ◽  
Vijayalakshmi Ravindranath ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Vitamin B ◽  
Vitamin B 12

scholarly journals Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruth Stephen ◽  
Mariagnese Barbera ◽  
Ruth Peters ◽  
Nicole Ee ◽  
Lidan Zheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Decline ◽  
Risk Reduction ◽  
Individual Risk ◽  
Who Guidelines ◽  
Dementia Risk ◽  
Dementia Prevention ◽  
Multidomain Intervention ◽  
Intervention Trials ◽  
Individual Risk Factors

The first WHO guidelines for risk reduction of cognitive decline and dementia marked an important milestone in the field of dementia prevention. In this paper, we discuss the evidence reviewed as part of the guidelines development and present the main themes emerged from its synthesis, to inform future research and policies on dementia risk reduction. The role of intervention effect-size; the mismatch between observational and intervention-based evidence; the heterogeneity of evidence among intervention trials; the importance of intervention duration; the role of timing of exposure to a certain risk factor and interventions; the relationship between intervention intensity and response; the link between individual risk factors and specific dementia pathologies; and the need for tailored interventions emerged as the main themes. The interaction and clustering of individual risk factors, including genetics, was identified as the overarching theme. The evidence collected indicates that multidomain approaches targeting simultaneously multiple risk factors and tailored at both individual and population level, are likely to be most effective and feasible in dementia risk reduction. The current status of multidomain intervention trials aimed to cognitive impairment/dementia prevention was also briefly reviewed. Primary results were presented focusing on methodological differences and the potential of design harmonization for improving evidence quality. Since multidomain intervention trials address a condition with slow clinical manifestation—like dementia—in a relatively short time frame, the need for surrogate outcomes was also discussed, with a specific focus on the potential utility of dementia risk scores. Finally, we considered how multidomain intervention could be most effectively implemented in a public health context and the implications world-wide for other non-communicable diseases targeting common risk factors, taking into account the limited evidence in low-middle income countries. In conclusion, the evidence from the first WHO guidelines for risk reduction of cognitive decline and dementia indicated that “one size does not fit all,” and multidomain approaches adaptable to different populations and individuals are likely to be the most effective. Harmonization in trial design, the use of appropriate outcome measures, and sustainability in large at-risk populations in the context of other chronic disorders also emerged as key elements.

scholarly journals Prestroke Statins, Progression of White Matter Hyperintensities, and Cognitive Decline in Stroke Patients with Confluent White Matter Hyperintensities

2014 ◽  
Vol 11 (3) ◽  
pp. 606-611 ◽  
Author(s):  
Yunyun Xiong ◽  
Adrian Wong ◽  
Margherita Cavalieri ◽  
Reinhold Schmidt ◽  
Winnie W. C. Chu ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Stroke Patients

Abstract TP181: Serum Eiocosapentaenoic Acids Is Protective Against White Matter Lesions

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Daiki Takano ◽  
Takashi Yamazaki ◽  
Tetsuya Maeda ◽  
Yuichi Satoh ◽  
Yasuko Ikeda ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
White Matter Hyperintensity ◽  
Partial Regression Coefficient ◽  
The Relationship ◽  
Total Pufa ◽  
Periventricular Hyperintensity

[Introduction] White matter hyperintensities (WMH) are considered manifestation of arteriosclerotic small vessel disease and WMH burden increases risk of ischemic stroke and cognitive decline. There are only a few evidences concerning the relationship between polyunsaturated fatty acids (PUFA) and WMH. The present study was designed to elucidate the association between WMH and PUFA profile including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in patients with Alzheimer’s disease (AD). [Methods] The present study was based on 119 patients who were diagnosed as having a probable AD according to the NINCDS-ADRDA criteria. Their mean age was 78.3 years old. All subjects underwent neuropsychological evaluation including mini mental state exam (MMSE) and 1.5-Tesla MRI. Fasting blood samples were also collected for the PUFA measurements. We measured the ratio of serum EPA, DHA and AA concentration to the total PUFA concentration. The WMH were evaluated on T2-weight images and classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The severity of WMH was graded 5 categories. We investigated the relationship between WMH and PUFA profiles. [Results] The EPA ratio correlated negatively with both PVH (rs=-0.2036, p=0.0264) and DWMH grade (rs=-0.3155, p=0.0005). It remained still significant after adjustment for age, sex, statins use, antithrombotics use, mean blood pressure and presence of hypertension (standardized partial regression coefficient(β)=-0.2516, p=0.0122 for PVH, β=-0.3598, p=0.0001 for DWMH). Neither DHA nor AA ratio correlated with DWMH or PVH grade. The EPA ratio but not DHA or AA ratio correlated positively with total MMSE score (rs=0.2310, p=0.0115). [Conclusions] Our data revealed that the serum EPA was protective against WMH as well as cognitive decline in AD patients. Pathophysiology underlying WMH is complex and the possible mechanisms involved in the pathogenesis of WMH encompass incomplete brain ischemia, increased permeability of blood-brain barrier, and inflammation responses. The relationship between serum EPA and WMH can be partly explained by those anti-ischemic and anti-arteriosclerotic effects of EPA.

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