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 < 0.001). Moreover, white matter hyperintensity volume was associated with greater cognitive decline from childhood to midlife (ß=−0.09, P < 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.

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.

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.

scholarly journals The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

2020 ◽  
Author(s):  
Mahsa Dadar ◽  
Richard Camicioli ◽  
Simon Duchesne ◽  
D. Louis Collins ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Amyloid Β ◽  
Disease Assessment ◽  
White Matter Hyperintensity ◽  
List Type ◽  
Temporal Relationships

ABSTRACTINTRODUCTIONCognitive decline in Alzheimer’s disease is associated with amyloid-β accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established.METHODSData included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimer’s Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1-42) for 461 participants from the Alzheimer’s Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and Aβ1-42 to changes in WMH, GM, Aβ1-42, and cognition at one-year follow-up.RESULTSBaseline WMHs and Aβ1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and Aβ1-42 predicted worsening cognition. Only baseline Aβ1-42 predicted change in Aβ1-42.DISCUSSIONBaseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage.Research in ContextSystematic Review: Both amyloid β and neurodegeneration are primary pathologies in Alzheimer’s disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimer’s. However, the temporal relationship between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline is still unclear.Interpretation: Our results establish a potential temporal order between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid β deposition, in turn, precedes accumulation of white matter hyperintensities.Future Directions: The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimer’s disease patients, in particular.

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 White matter hyperintensities may be an early marker for age-related cognitive decline in the ADNI cohort

2021 ◽  
Author(s):  
Cassandra Morrison ◽  
Mahsa Dadar ◽  
Sylvia Villeneuve ◽  
D. Louis Collins
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
White Matter Hyperintensity ◽  
Subjective Cognitive Decline ◽  
Age Related ◽  
Lower Baseline ◽  
Age Related Cognitive Decline ◽  
Linear Regressions

Background: Previous research suggests that white matter hyperintensities, amyloid, and tau contribute to age-related cognitive decline. It remains unknown as to how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline. Methods: Cognitively normal older adult data from the Alzheimers Disease Neuroimaging Initiative were examined. Participants were included if they had no subjective cognitive decline, had baseline white matter hyperintensity, CSF AB42/40, CSF pTau181, and cognitive scores. Of the 102 participants included, only 79 had follow-up cognitive scores. Linear regressions examined the influence of white matter hyperintensities, amyloid, and tau on baseline and follow-up cognitive scores. Linear regressions also examined the association of amyloid and tau on white matter hyperintensities and between tau and amyloid. Results: Increased white matter hyperintensity load was associated with lower baseline memory (B= -0.20, p =.046), follow-up executive functioning (B= -0.32, p<.001), and follow-up ADAS-13 (B=2.69, p<.001) scores. White matter hyperintensities were not related to pTau or AB42/40. Lower AB42/40 was associated with increased pTau (p=.025). pTau was not associated with decline in any cognitive score. Lower AB42/40 was associated with lower baseline (p=.015) but not follow-up executive function. Discussion: White matter hyperintensities may be one of the earliest pathologies observed in healthy older adults that contribute to cognitive decline. The inclusion of white matter hyperintensities as an additional marker for early cognitive decline may improve our current understanding of age-related changes.

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.

scholarly journals The Preservation of Cognition 1 Year After Carotid Endarterectomy in Patients With Prior Cognitive Decline

Neurosurgery ◽  
2017 ◽  
Vol 82 (3) ◽  
pp. 322-328 ◽  
Author(s):  
Robert J Dempsey ◽  
Daren C Jackson ◽  
Stephanie M Wilbrand ◽  
Carol C Mitchell ◽  
Sara E Berman ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Carotid Endarterectomy ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Unstable Plaque ◽  
Medical Risk ◽  
Plaque Instability ◽  
Brain White Matter ◽  
Asymptomatic Patients

Abstract BACKGROUND Vascular cognitive decline is critically important in the course of atherosclerosis and stroke. OBJECTIVE To explore the hypothesis that carotid endarterectomy (CEA) by removing an unstable plaque may slow the course of vascular cognitive decline in both symptomatic and asymptomatic patients. METHODS Patients with clinically significant (&gt;60%) carotid stenosis were studied preop and 1 yr post-CEA for clinical symptoms, vascular cognitive decline, instability of carotid plaque—presence of microemboli, brain white matter changes, and medical risk factors. RESULTS Forty-six percent were classically symptomatic. All patients showed vascular cognitive decline at presentation which correlated with degree of plaque instability. Significant white matter hyperintensity changes (48.7%) and cerebral emboli (25%) were also seen at baseline in both classically symptomatic and asymptomatic. One year after CEA, both groups showed no decline in cognitive function and significant improvement in 2 tests (P = .028 and P = .013). Brain white matter hyperintensities were unchanged. Microemboli were reduced but remained present (17.86%). Improvement was predicted by the presence of hypertension (P = .001), or less advanced cognitive decline preoperatively (P = .009). CONCLUSION This study demonstrates the importance of vascular cognitive decline in atherosclerotic disease. This is a function of the degree of instability of the atherosclerotic plaque more than the presence of stroke symptoms. It further suggests that atherosclerotic vascular cognitive decline need not be inevitable, and may be modified by treating hypertension and removal of the unstable plaque. This highlights the need for continued research on the cognitive effects of cerebrovascular disease and the synergistic benefits of intensive medical and surgical therapy.

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
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