Microinfarcts are common and strongly related to dementia in the oldest‐old: The 90+ study

Corrada, María M.; Sonnen, Joshua A.; Kim, Ronald C.; Kawas, Claudia H.

doi:10.1016/j.jalz.2016.04.006

Cited by 56 publications

(53 citation statements)

References 28 publications

(56 reference statements)

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“…Our findings in PANDA ADC participants highlight that clinical impairment due to VBI may be detectable only in those with multiple VBI, similar to other studies [9,32]. Interestingly, only subcortical microinfarcts were associated with progression, in contrast to other studies finding associations between cortical microinfarcts and cognitive impairment [34,35]. Future studies may be useful to assess the impact of other types of vascular pathologies, such as specific vessel disorders, on progression in mixed ADNP.…”

Section: Discussionsupporting

confidence: 88%

“…VBI was defined as any gross infarcts (small or large artery) or any cortical microinfarcts (infarcts in the cortex only seen microscopically) regardless of age. Some studies suggest multiple VBI, in particular microinfarcts, may be needed to affect cognition [32,34]. Information on number of microinfarcts were not available for most NACC participants.…”

Section: Methodsmentioning

confidence: 99%

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Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample

Brenowitz

Hubbard

Keene

et al. 2016

Alzheimer's & Dementia

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INTRODUCTION Whether co-occurring neuropathologies interact or independently affect clinical disease progression is uncertain. We estimated rates of clinical progression and tested whether associations between clinical progression and Alzheimer’s disease neuropathology (ADNP) were modified by co-occurring Lewy body disease (LBD) or vascular brain injury (VBI). METHODS Linear mixed effects models evaluated longitudinal trends in the Clinical Dementia Rating Sum of Boxes on 2,046 autopsied participants seen at a U.S. Alzheimer’s Disease Center. RESULTS Annual clinical progression was slightly faster for ADNP+LBD compared to ADNP only (p=0.06) and slightly slower for ADNP+VBI (p=0.003). Differences in progression were less than expected if each neuropathology independently contributed to progression; ADNP interacted with LBD (p=0.002) and VBI (p=0.003). In secondary models, the effect of additional pathologies on clinical progression was greater in those with intermediate compared to high levels of ADNP. DISCUSSION The impact of co-occurring pathologies on progression may depend on severity of ADNP.

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Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample

Brenowitz

Hubbard

Keene

et al. 2016

Alzheimer's & Dementia

View full text Add to dashboard Cite

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“…Microinfarcts are increasingly recognized in large community-based cohorts [4,50,75,112,120] and in persons older than 90, the oldest old [25]. Estimates of microinfarct prevalence in the elderly range from 16% to 46% [4,50,75,112,122], and jump to 51% in the oldest old [25].…”

Section: Mixed Vascular and Ad Pathologiesmentioning

confidence: 99%

“…Estimates of microinfarct prevalence in the elderly range from 16% to 46% [4,50,75,112,122], and jump to 51% in the oldest old [25]. Indeed, microinfarcts are also highly prevalent in persons with probable AD, vascular dementia, and mixed dementia [19,43,130].…”

Section: Mixed Vascular and Ad Pathologiesmentioning

confidence: 99%

Impact of multiple pathologies on the threshold for clinically overt dementia

2017

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Longitudinal clinical-pathologic studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development Alzheimer’s disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis). These additional pathologies lower the threshold for clinical diagnosis of AD. Many of these findings from pathologic studies, especially for CVD, have been confirmed using sophisticated neuroimaging technologies. In-vivo biomarker studies are necessary to provide an understanding of specific pathologic contributions and time course relationships along the spectrum of accumulating pathologies. In this review, we provide a clinical-pathological perspective on the role of multiple brain pathologies in dementia followed by a review of the available clinical and biomarker data on some of the mixed pathologies.

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“…Lacunar infarcts are miliary softenings from 3 to 15 mm diameter, found in 32-45% of elderly as the most frequent types of CVLs [17]. They are common and strongly related to dementia in the oldest-old [27].…”

Section: Small Vessel Disease (Svd)/microangiopathic Dementiamentioning

confidence: 99%

Current Pathogenetic Concepts of Vascular Cognitive Impairment

Jellinger¹

2016

J Neurol Neurol Sci Disord

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The term vascular cognitive impairment designates a heterogenous group of disorders ranging from mild cognitive impairment to full-blown dementia -vascular dementia -resulting from cerebrovascular lesions involving various brain areas. Current clinical criteria show moderate sensitivity (50-56%) and variable specifi city (range 64-98%). The prevalence in autopsy series ranges from 0.03 to 58% (mean 8-15% in Western series, 22-35% in Japan). Major morphological types -multi-infarct and subcortical vascular encephalopathy, strategic infarct dementia, lacunar state, cortical granular atrophy (rare), and ischemic encephalopathy -are caused by atherosclerosis of major cerebral arteries and small vessel disease, resulting from systemic, cardiac and local vascular disease or cerebral amyloid angiopathy. Pathogenesis of vascular dementia is multifactorial, and pathophysiology affects brain areas and neurological networks involved in cognition, memory, behavior, and executive functions. Vascular brain injury in elderly persons often coexists with Alzheimer-type lesions and other pathologies resulting in mixed dementia. However, these lesions are also present in many non-demented elderly subjects. The heterogeneity of clinical manifestations, cerebrovascular pathology and their pathogenic factors result in limitations of the accuracy of diagnostic criteria for vascular dementia. Therefore, standardized and reproducible neuropathological criteria for the assessment of cerebrovascular lesions associated with cognitive impairment in order to elucidate contribution of cerebrovascular disease to cognitive impairment are urgently needed.

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Microinfarcts are common and strongly related to dementia in the oldest‐old: The 90+ study

Cited by 56 publications

References 28 publications

Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample

Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample

Impact of multiple pathologies on the threshold for clinically overt dementia

Current Pathogenetic Concepts of Vascular Cognitive Impairment

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