Brain Infarction and the Clinical Expression of Alzheimer Disease<subtitle>The Nun Study</subtitle>
Abstract
Objective. —To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Design. —Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Setting. —Convents in the Midwestern, Eastern, and Southern United States. Participants. —A total of 102 college-educated women aged 76 to 100 years. Main Outcome Measures. —Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Results. —Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7,95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. Conclusion. —These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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Population-autopsy series verified the high frequency and pathogenetic importance of combined Alzheimer disease and vascular disease in the expression of dementia.
“Population-autopsy series verified the high frequency and pathogenetic importance of combined Alzheimer disease and vascular disease in the expression of dementia as mentioned previously.”
Vascular lesions can lower the threshold for the clinical manifestation of Alzheimer disease.
“Furthermore, vascular lesions can lower the threshold for the clinical manifestation of Alzheimer disease.”
Several studies have found that in patients with Alzheimer disease and cerebrovascular disease, less Alzheimer disease pathology is needed to express the dementia syndrome.
“Several studies have found that in patients with Alzheimer disease and cerebrovascular disease, less Alzheimer disease pathology is needed to express the dementia syndrome.”
Infarcts typically are accompanied by Alzheimer disease and other pathologies.
“typically are accompanied by Alzheimer disease and other pathologies.”
Infarcts frequently coexist with Alzheimer disease pathology in the brains of older people.
“Infarcts frequently coexist with Alzheimer disease pathology in the brains of older people.”
One study showed that only people with Alzheimer disease pathology with subcortical infarcts had dementia, raising the possibility of an interaction (a multiplicative effect) between the 2 pathologies.
“One study showed that only people with Alzheimer disease pathology with subcortical infarcts had dementia, raising the possibility of an interaction (a multiplicative effect) between the 2 pathologies.”
It is now accepted that many traditional stroke risk factors are also risk markers for Alzheimer disease and VCI.
“It is now accepted that many of the traditional risk factors for stroke are also risk markers for Alzheimer disease and VCI.16,31,340,484–491”
Lacunes are frequently seen on imaging in elderly patients without symptoms.
“Lacunes are frequently seen on imaging in elderly patients with no symptoms”
From Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration (2013) · cites this paper as [25]
Lacunes are associated with an increased risk of stroke, gait impairment, and dementia.
“are associated with an increased risk of stroke, gait impairment, and dementia.”
From Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration (2013) · cites this paper as [25]
Cerebrovascular effects of APOE4 are associated with AD, stroke, and brain hemorrhage.
“Cerebrovascular effects of APOE4 are associated with AD, stroke, and brain hemorrhage (314, 506, 549, 614, 693).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [549]
Classical anatomic locations for strategic infarcts include the thalamus, angular gyrus, and basal ganglia, including the caudate nucleus and globus pallidus.
“Classical anatomic locations for strategic infarcts include the thalamus, angular gyrus, and basal ganglia, including the caudate nucleus and globus pallidus. 52-57”
From Vascular Cognitive Impairment (2017) · cites this paper as [56]
A single small infarct may cause severe cognitive deficits when located in a strategic brain region.
“A single small infarct may cause severe cognitive deficits when located in a strategic brain region.”
From Vascular Cognitive Impairment (2017) · cites this paper as [56]
Vascular brain lesions lower the threshold of AD pathology required to induce dementia.
“However, vascular brain lesions lower the threshold of AD pathology required to induce dementia. 56,100-102”
From Vascular Cognitive Impairment (2017) · cites this paper as [56]
Earlier studies have suggested a multiplicative effect between vascular and AD-type pathology on cognitive decline, whereas recent studies indicate that the effects are additive.
“Earlier studies have suggested a multiplicative effect between vascular and AD-type pathology on cognitive decline, 56 whereas recent studies indicate that the effects are additive. 49,100,105”
From Vascular Cognitive Impairment (2017) · cites this paper as [56]
Many older people with dementia have combined vascular and Alzheimer-type pathology, and the two pathologies have an additive effect on cognition.
“many older individuals with dementia suffer from a combination of vascular and Alzheimer-type pathology with an additive effect on cognition,19”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [19]
In older individuals with moderate Alzheimer disease pathology, subcortical vascular lesions are a major determinant of dementia expression.
“On the other hand, in older individuals with moderate AD pathology subcortical vascular lesions are a major determinant of the expression of the dementia (Esiri et al., 1999; Schneider et al., 2007b; Snowdon et al., 1997).”
From The Pathobiology of Vascular Dementia (2013) · cites this paper as Snowdon et al., 1997
It is reasonable to postulate that insulin resistance and type 2 diabetes could increase Alzheimer's disease risk through cerebrovascular disease.
“it seems reasonable to postulate that insulin resistance and T2D could increase AD risk through cerebrovascular disease, a factor increasingly accepted to be important in AD manifestation [5, 19-21].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [5]
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- Authors
- Snowdon, D. A.
- Corresponding author
- Snowdon, David A.
- ORCID
- Snowdon, David A.
- Venue
- JAMA: The Journal of the American Medical Association
- Publisher
- American Medical Association (AMA)
- Published
- 1997-03-12
- Volume
- 277
- Issue
- 10
- Pages
- 813
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W4296588155
- Cited by
- 1,590
- References
- 0
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 30 · 2023: 39 · 2022: 43 · 2021: 42 · 2020: 51 · 2019: 57 · 2018: 52 · 2017: 60 · 2016: 74 · 2015: 63 · 2014: 71 · 2013: 61 · 2012: 74
- FWCI
- 34.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- Funders
- National Institute on Aging (R01AG009862, P50AG005144, KO4AG00553)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, cerebral infarction, lacunar infarction, dementia, cognitive function, amyloid plaques, neurofibrillary tangles, cerebrovascular disease, atherosclerosis, circle of Willis, thalamic infarction, basal ganglia infarcts, older women, neuropathology
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