Microvascular Burden and Alzheimer-Type Lesions Across the Age Spectrum
Open accessAbstract
The occurrence of microvascular and small macrovascular lesions and Alzheimer's disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between macroscopic vascular lesions and incident dementia, the cognitive consequences of the progressive accumulation of these small vascular lesions in the human brain are still a matter of debate. Among the vast group of small vessel-related forms of ischemic brain injuries, the present review discusses the cognitive impact of cortical microinfarcts, subcortical gray matter and deep white matter lacunes, periventricular and diffuse white matter demyelinations, and focal or diffuse gliosis in old age. A special focus will be on the sub-types of microvascular lesions not detected by currently available neuroimaging studies in routine clinical settings. After providing a critical overview of in vivo data on white matter demyelinations and lacunes, we summarize the clinicopathological studies performed by our center in large cohorts of individuals with microvascular lesions and concomitant AD-related pathology across two age ranges (the younger old, 65-85 years old, versus the oldest old, nonagenarians and centenarians). In conjunction with other autopsy datasets, these observations fully support the idea that cortical microinfarcts are the only consistent determinant of cognitive decline across the entire spectrum from pure vascular cases to cases with combined vascular and AD lesion burden.
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Together with cortical microinfarcts, WMLs may contribute to the progression of cognitive impairment.
“Together with cortical microinfarcts, WMLs may contribute to the progression of cognitive impairment, but do not necessarily interact with AD pathology to increase the likelihood of dementia beyond their additive effect [20].”
From The overlap between vascular disease and Alzheimer’s disease - lessons from pathology (2014) · cites this paper as [20]
WMLs do not necessarily interact with AD pathology to increase the likelihood of dementia beyond their additive effect.
“Together with cortical microinfarcts, WMLs may contribute to the progression of cognitive impairment, but do not necessarily interact with AD pathology to increase the likelihood of dementia beyond their additive effect [20].”
From The overlap between vascular disease and Alzheimer’s disease - lessons from pathology (2014) · cites this paper as [20]
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Costanza, A., Amerio, A., Aguglia, A., Serafini, G., Amore, M., Macchiarulo, E., Branca, F., & Merli, R. (2021) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v92is6.12249 · Cited by 45 · see citing works
“which the neural injury overlaps hopelessness (34-36),”
Self-citationCostanza, A., Macheret, L., Folliet, A., Amerio, A., Aguglia, A., Serafini, G., Prada, P., Bondolfi, G., Sarasin, F., & Ambrosetti, J. (2021) · Medicina · doi:10.3390/medicina57121360 · Cited by 44 · see citing works
Self-citationMarkers of cerebral small vessel disease and severity of depression in the general population
Direk, N., Pérez, H. C. S., Akoudad, S., Verhaaren, B. F. J., Niessen, W. J., Albert Hofman, D., Vernooij, M. W., Ikram, M. A., & Tiemeier, H. W. (2016) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2016.05.002 · Cited by 41 · see citing works
Pathogenesis and Treatment of Vascular Cognitive Impairment
Jellinger, K. A. (2014) · Neurodegenerative Disease Management · doi:10.2217/nmt.14.37 · Cited by 30 · see citing works
Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis
Bickel, M. A., Csík, B., Gulej, R., Ungvari, A., Nyúl‐Tóth, Á., & Conley, S. M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1087053 · Cited by 28 · see citing works
Huang, C. B., Luo, J., Wen, X., & Li, K. (2021) · Biochemical Genetics · doi:10.1007/s10528-021-10154-8 · Cited by 27 · see citing works
Liu, H., Zhang, X., Liu, H., & Chong, S. T. (2023) · International Journal of Public Health · doi:10.3389/ijph.2023.1605322 · Cited by 27 · see citing works
“Cognitive impairment is an age-related condition caused by Alzheimer’s disease, vascular dementia, mixed dementia or other related types of dementias with no cure [23, 24].”
BackgroundWeidung, B., Littbrand, H., Nordström, P., Carlberg, B., & Gustafson, Y. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000000831 · Cited by 26 · see citing works
Costanza, A., Radomska, M., Zenga, F., Amerio, A., Aguglia, A., Serafini, G., Amore, M., Berardelli, I., Ojio, Y., & Nguyen, K. D. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18030876 · Cited by 17 · see citing works
Self-citationCostanza, A., Amerio, A., Aguglia, A., Magnani, L., Serafini, G., Amore, M., Merli, R., Ambrosetti, J., Bondolfi, G., Marzano, L., et al. (2021) · Brain Sciences · doi:10.3390/brainsci11121594 · Cited by 15 · see citing works
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Costanza, A., Placenti, V., Amerio, A., Aguglia, A., Serafini, G., Amore, M., Macchiarulo, E., Branca, F., Merli, R., Bondolfi, G., et al. (2021) · Behavioral Sciences · doi:10.3390/bs11110154 · Cited by 12 · see citing works
“This risk was particularly signalized among patients in co-treatment with metformin or elderly (possibly due to diminished neuronal reserve and presence of mixed neurodegenerative and vascular brain injuries) [23,26,30].”
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“Microglia activation was also observ d in some of these brain r gions in patients with Alzheimer’s disease (AD) and affective disorders [23,24], suggesting the possible existence of microglia reactivity against a common dysfunctional neuronal circuit among various CNS disorders.”
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“Initial research accentuated the importance of not overlooking microvascular and diminutive macrovascular lesions within the purview of cognitive decline studies and interventions, as they represent the pivotal pathological element exacerbating cognitive deterioration [28,29].”
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Influencing factors of psychological pain among older people in China: A cross-sectional study
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“Neurobiological evidence also suggests that psychological pain may be related to cognitive decline [5].”
BackgroundInflammatory pathology in depression and suicide: a mechanistic distillation of clinical correlates
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“Some minor impairments, such as cortical microinfacts, have been confirmed to be the only subtype of microvascular lesions, which is a consistent determinant of cognitive decline across the age spectrum from vascular to mixed dementia (Costanza et al., 2012).”
BackgroundLiu, Y., Wu, W.-H., Tseng, W., Lin, H.-C., Wu, M., Chen, P., & Wu, I. (2023) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2023.111492 · Cited by 5 · see citing works
Degenerative Brain Diseases and White Matter Injury
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Fluctuating criteria for a fluctuating disorder
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(2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-32419
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Self-citation
- Authors
- Costanza, A., Xekardaki, A., Kövari, E., Gold, G., Bouras, C., & Giannakopoulos, P.
- Affiliations
- University of Geneva (CH)
- Department of Psychiatry, University Hospitals and Faculty of Medicine of Geneva, Belle-Idée, Geneva, Switzerland
- ORCID
- Costanza, Alessandra
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2012-10-29
- Volume
- 32
- Issue
- 3
- Pages
- 643-652
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1894778983
- Cited by
- 36
- References
- 97
- Citations by year
- 2024: 1 · 2023: 12 · 2022: 1 · 2021: 7 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- microvascular lesions, Alzheimer's disease
- MeSH terms
- Aging, Alzheimer Disease, Animals, Cerebrovascular Circulation, Humans, Microcirculation
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