The association between white matter hyperintensities and amyloid and tau deposition

Alban, Sierra; Lynch, Kirsten M.; Ringman, John M.; Toga, Arthur W.; Chui, Helena C.; Sepehrband, Farshid; Choupan, Jeiran

doi:10.1016/j.nicl.2023.103383

Cited by 12 publications

(9 citation statements)

References 116 publications

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“…Additionally, WMH has been increasingly recognized as a marker of small vessel disease and is posited to contribute to cognitive decline in AD. While mounting evidence links increased WMH volume to Aβ, tau and small vessel neuropathology, other studies suggest it may reflect AD-related Wallerian degeneration in later disease stages [21,35–37]. Our findings of a consistent association between WMH and Aβ-PET positivity across all cognitive stages suggest a stable and independent relationship with Aβ neuropathology.…”

Section: Discussionsupporting

confidence: 46%

Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

Howe,

Caruso,

Manoochehri

et al. 2024

Preprint

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INTRODUCTION: The relationship between cerebrovascular disease (CVD) and amyloid-β (Aβ) in Alzheimer disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers, including cerebral microbleeds (CMBs), ischemic infarction, and white matter hyperintensities (WMH), would correlate with Aβ positivity on positron emission tomography (Aβ-PET). METHODS: We cross-sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N=1,352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth. RESULTS: Following adjustment, WMH (OR=1.25) and superficial CMBs (OR=1.45) remained positively associated with Aβ-PET positivity (p<.001). Deep CMBs and infarcts exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R2=.41). DISCUSSION: The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria. ClinicalTrials.gov: ADNI-2 (NCT01231971), ADNI-3 (NCT02854033)

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Section: Discussionsupporting

confidence: 46%

Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

Howe,

Caruso,

Manoochehri

et al. 2024

Preprint

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“…In a longitudinal study, Bombois et al (2008) found a significant relationship between a large amount of subcortical WMH at baseline and a higher risk of developing vascular or mixed dementia. A recent study by Alban et al (2023) reported an association between the incidence of WMH and β-amyloid accumulation, which is a biomarker for the development of dementia due to Alzheimer’s disease. Therefore, the results of previous investigations suggest that patients with cardiovascular disease could be at higher risk of developing dementia due to Alzheimer’s disease, vascular dementia, or mixed dementia.…”

Section: Discussionmentioning

confidence: 99%

Influence of mild cognitive impairment on clinical and functional prognosis in older candidates for cardiac surgery

Harmand,

Mata,

Prada-Arrondo

et al. 2024

Front. Hum. Neurosci.

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IntroductionIn this study, we analyzed the prognostic impact of mild cognitive impairment (MCI) prior to cardiac surgery on 12-month clinical outcomes in older patients.MethodWe performed a longitudinal prospective study of 48 patients undergoing cardiac surgery and 26 neurologically healthy participants aged 65 years or older. All participants underwent a neuropsychological assessment. Functional status, quality of life and frailty were assessed in candidates for surgery. One year after surgery, 24 patients remained in the study.ResultsMild cognitive impairment (MCI) was diagnosed in 35% of the patients at baseline. Postsurgical changes in functionality consisted of a tendency toward impaired basic activities of daily living (BADL) in the MCI group and a statistically significant worsening in instrumental activities of daily living (IADL) in women with MCI. Changes in quality of life consisted of a significant improvement in anxiety-depression in the MCI group and a tendency toward greater pain-discomfort in the non-MCI group. Cognitive status significantly declined only in the non-MCI group. Neither group showed significant changes in frailty. Relative risk analysis showed that patients with a diagnosis of MCI at baseline had a higher risk of cognitive decline at follow-up, while those without a diagnosis of MCI at baseline had a lower risk of impaired IADL. No association was found between MCI and resource use. Preoperative impairment in memory, visuospatial and executive functions was significantly associated with loss of quality of life at follow-up. Impairment of memory and visuospatial function was significantly associated with cognitive decline. Preserved memory was associated with a lower risk of impaired BADL at follow-up.ConclusionThe present study provides clue on the impact of MCI in candidates for cardiac surgery. Preoperative detection of cognitive impairment could be highly valuable to help guide pre- and post-operative management.

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“…However, there is evidence in the literature of associations between amyloid and white matter hyperintensities [ 40 ]. Furthermore, the association observed between WMH volumes and the Tau-FDG correlation is in line with a post-mortem study reporting association between cortical tau load and white matter lesions [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Suspecting Non-Alzheimer’s Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images

Malotaux,

Colmant,

Quenon

et al. 2024

JAD

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Background: Alzheimer’s disease (AD) pathology can be disclosed in vivo using amyloid and tau imaging, unlike non-AD neuropathologies for which no specific markers exist. Objective: We aimed to compare brain hypometabolism and tauopathy to unveil non-AD pathologies. Methods: Sixty-one patients presenting cognitive complaints (age 48–90), including 32 with positive AD biomarkers (52%), performed [18F]-Fluorodeoxyglucose (FDG)-PET (brain metabolism) and [18F]-MK-6240-PET (tau). We normalized these images using data from clinically normal individuals (n = 30), resulting in comparable FDG and tau z-scores. We computed between-patients correlations to evaluate regional associations. For each patient, a predominant biomarker (i.e., Hypometabolism > Tauopathy or Hypometabolism≤Tauopathy) was determined in the temporal and frontoparietal lobes. We computed within-patient correlations between tau and metabolism and investigated their associations with demographics, cognition, cardiovascular risk factors (CVRF), CSF biomarkers, and white matter hypointensities (WMH). Results: We observed negative associations between tau and FDG in 37 of the 68 cortical regions-of-interest (average Pearson’s r = –0.25), mainly in the temporal lobe. Thirteen patients (21%) had Hypometabolism > Tauopathy whereas twenty-five patients (41%) had Hypometabolism≤Tauopathy. Tau-predominant patients were more frequently females and had greater amyloid burden. Twenty-three patients (38%) had Hypometabolism≤Tauopathy in the temporal lobe, but Hypometabolism > Tauopathy in the frontoparietal lobe. This group was older and had higher CVRF than Tau-predominant patients. Patients with more negative associations between tau and metabolism were younger, had worse cognition, and greater amyloid and WMH burdens. Conclusions: Tau-FDG comparison can help suspect non-AD pathologies in patients presenting cognitive complaints. Stronger Tau-FDG correlations are associated with younger age, worse cognition, and greater amyloid and WMH burdens.

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The association between white matter hyperintensities and amyloid and tau deposition

Cited by 12 publications

References 116 publications

Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

Influence of mild cognitive impairment on clinical and functional prognosis in older candidates for cardiac surgery

Suspecting Non-Alzheimer’s Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images

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