Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Rizvi, Batool; Sathishkumar, Mithra; Kim, Soyun; Márquez, Freddie; Granger, Steven J.; Larson, Myra S; Miranda, Blake A; Hollearn, Martina K; McMillan, Liv; Nan, Bin; Tustison, Nicholas J.; Lao, Patrick J.; Brickman, Adam M.; Greenia, Dana; Corrada, María M.; Kawas, Claudia H.; Yassa, Michael A.

doi:10.1016/j.nicl.2022.103308

Cited by 7 publications

(9 citation statements)

References 48 publications

(62 reference statements)

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“…The findings presented identify cerebrovascular pathology as a candidate mechanism driving MTL degeneration associated with OSA-related hypoxemia. Prior studies also support this possibility, suggesting a strong link between WMH burden and MTL atrophy 143–146 which the present findings extend by implicating hypoxic burden during REM sleep as a contributor to this link. AD patients with periventricular WMH had a significantly increased risk of progression of MTL atrophy compared to those without baseline periventricular WMH 144 .…”

Section: Discussionsupporting

confidence: 85%

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Berisha,

Rizvi,

Chappel-Farley

et al. 2024

Preprint

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Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

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Section: Discussionsupporting

confidence: 85%

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Berisha,

Rizvi,

Chappel-Farley

et al. 2024

Preprint

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“…We assessed the associations of these blood pressure measures with MRI markers of cerebrovascular disease, entorhinal cortical thickness, and clinical diagnosis of dementia. Previously, we showed that parietal and occipital lobe WMH are associated with medial temporal lobe atrophy in community-dwelling older adults 40-42 . Prior work also demonstrated that greater parietal and occipital lobe WMH burden is predictive of a diagnosis of dementia in adults with DS and in autosomal dominant AD 19,43 .…”

Section: Introductionmentioning

confidence: 90%

“…Previously, we showed that parietal and occipital lobe WMH are associated with medial temporal lobe atrophy in community-dwelling older adults [40][41][42] . Prior work also demonstrated that greater parietal and occipital lobe WMH burden is predictive of a diagnosis of dementia in adults with DS and in autosomal dominant AD 19,43 .…”

Section: Introductionmentioning

confidence: 91%

Pathways linking pulse pressure to dementia in adults with Down syndrome

Rizvi,

Lao,

Sathishkumar

et al. 2023

Preprint

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Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS. Participants with DS from the Biomarkers of Alzheimer's Disease in Adults with Down Syndrome study (ADDS; n = 195, mean age (SD) = 50.6 (7.2), 44% women, 18% diagnosed with dementia) were included. Higher pulse pressure was associated with greater global, parietal, and occipital WMH volume. Pulse pressure was not related to enlarged PVS, microbleeds, infarcts, entorhinal cortical thickness, or dementia diagnosis. However, in a serial mediation model, we found that pulse pressure was indirectly related to dementia diagnosis through parieto-occipital WMH and, subsequently through entorhinal cortical thickness. Higher pulse pressure may be a risk factor for dementia in people with DS by promoting cerebrovascular disease, which in turn affects neurodegeneration. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

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“…The relationship between WMH and hippocampal volume in mild cognitive impairment (MCI) and AD patients is inconclusive, showing associations in some studies that relied on clinically defined MCI 5–9 or AD, 8–11 but rarely evaluated in the presence of Aβ or tau biomarkers 8,9 . Additionally, little is known about the effect of regional SVD on hippocampal structure, which has not yet been investigated in the context of AD‐related biomarkers 5,6,12 . Converging evidence supports a link between the spatial distribution of WMH and distinct pathophysiological mechanisms in AD, with anterior WMH mostly linked to deficits in regional perfusion, and posterior WMH more specifically associated with AD, highlighting the utility of a regionalized approach to reveal how SVD and AD pathologies may coexist and interact 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology

Xhima,

Ottoy,

Gibson

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONCerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co‐exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood.METHODSIn a unique cohort of mixed Alzheimer's disease and moderate–severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18F‐AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape.RESULTSFrontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ‐vulnerable subregions.DISCUSSIONHippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease‐specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

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Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Cited by 7 publications

References 48 publications

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Pathways linking pulse pressure to dementia in adults with Down syndrome

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology

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