AD lesions and infarcts in demented and non‐demented Japanese‐American men

Petrovitch, Helen; Ross, G. Webster; Steinhorn, Sandra C.; Abbott, Robert D.; Markesbery, William R.; Davis, Daron G.; Nelson, James S.; Hardman, John; Masaki, Kamal; Vogt, Margaret R.; Launer, Lenore J.; White, Lon R.

doi:10.1002/ana.20318

Cited by 210 publications

(168 citation statements)

References 33 publications

(35 reference statements)

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“…This is similar to the situation in individuals with very low levels of both neocortical AD lesions. [35] Additional analyses completed since that report, confirmed that both lacunes and large vessel infarcts were slightly more frequent in the NFT only group (49.4% had lacunes, and 39.5% had large infarcts) compared to the NP only group (42.9% had lacunes, and 31.4% had large vessel infarcts).…”

Section: Discussionmentioning

confidence: 73%

“…In a recent report from the HAAS, [35] both the NP only and the NFT only groups had low proportions of demented individuals similar to the no AD lesion group unless a concomitant CV lesion was also present (6.3% demented for the NP only group, and 10.7% demented for the NFT only group, compared to 20% demented for the no AD lesion group). However when at least one lacune or infarct was present, 45% of the NP only group and 46% of the NFT only group were found to be demented.…”

Section: Discussionmentioning

confidence: 88%

“…In the HonoluluAsia Aging Study (HAAS) cohort of Japanese-American men in Hawaii, there are numerous individuals in the autopsy series whose brains have either neocortical NP or NFT in isolation. [35] A previous publication demonstrated that there was no increased probability of dementia for either of these two single lesion type groups or a group with low frequencies of both lesion types (early AD process) compared to those without AD lesions. However, when concurrent focal ischemic cerebrovascular (CV) lesions were found at autopsy, rates of dementia more than doubled for all three groups.…”

Section: Introductionmentioning

confidence: 90%

“…In contrast, although men with no neocortical AD lesions had low probability of dementia, and those with high frequencies of both NP and NFT in the neocortex had a significantly higher probability of dementia, CV lesions had little effect on rates of dementia in either of these groups. [35] This led to the speculation that the NP only and NFT only groups could represent early AD processes, similar to those who had low frequencies of both NP and NFT in the neocortex. If this were true, and if the pathogenesis of isolated neocortical NFT and NP were similar to that for combined lesions, the three groups might be expected to share other clinical and pathological features.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Japanese-American men with a single neocortical AD lesion type

Petrovitch

Ross

et al. 2008

Neurobiology of Aging

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Neocortical neuritic plaques (NP) and neurofibrillary tangles (NFT) are hallmarks of Alzheimer's disease (AD) and usually, both are present. The Honolulu-Asia Aging Study autopsy series includes a significant number of individuals with only one neocortical AD lesion type. These could represent an early phase of the AD process. If so, such individuals would be expected to share other clinical and pathological features of AD. We compared frequency of apolipoprotein epsilon E4 (APOE4) allele, average Braak stage, and burden of cerebral amyloid angiopathy (CAA) among the two single lesion type groups, a group without AD lesions, and groups with high and low frequencies of both AD lesions. Single AD lesion groups shared only the characteristics associated with their unique lesion type with the combined AD lesion group and did not have higher prevalence of dementia than the no AD lesion group. Only the NP+NFT group showed a "dose response" relationship with greater probability of dementia with higher neocortical frequencies of either AD lesion. The single neocortical AD lesion groups do not appear to represent early AD.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Characterization of Japanese-American men with a single neocortical AD lesion type

Petrovitch

Ross

et al. 2008

Neurobiology of Aging

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“…Intracranial atherosclerosis is a major cause of brain hypoperfusion and stroke. Furthermore, infarcts are present in approximately 40% of subjects with AD and the presence of infarcts has been shown to significantly increase the likelihood of dementia in subjects harboring both infarcts and AD histopathology [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

P2‐107: Intracranial Atherosclerosis as a contributing factor to Alzheimer's disease Dementia

Kokjohn

Maarouf

Sabbagh

et al. 2009

Alzheimer's & Dementia

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Background-A substantial body of evidence amassed from epidemiologic, correlative and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating what is presently the inexorable course of dementia. To assess this hypothesis it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis.Methods-A precise neuropathological diagnosis was established for all subjects using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis (CW) was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and compared between AD and non-demented control (NDC) groups by calculating a corresponding index of occlusion. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptAlzheimers Dement. Author manuscript; available in PMC 2012 July 1. Results-Atherosclerotic occlusion of the CW arteries was more extensive in the AD group than the NDC group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total NFT score, total white matter rarefaction score, brain weight, MMSE scores and apolipoprotein E allelic frequencies.Conclusions-Our results, combined with a consideration of the multifaceted impacts of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using anti-atherosclerotic agents.

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Magnetic Resonance Imaging White Matter Hyperintensities and Brain Volume in the Prediction of Mild Cognitive Impairment and Dementia

Smith¹,

et al. 2008

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To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia.Design: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean.Setting: General community.Patients: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI).Main Outcome Measures: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at base-line). Cox proportional hazards models were used for multivariable analysis.Results: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P=.01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P = .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; PϽ.001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P =.03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P =.02), but not AD dementia.Conclusions: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.

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AD lesions and infarcts in demented and non‐demented Japanese‐American men

Cited by 210 publications

References 33 publications

Characterization of Japanese-American men with a single neocortical AD lesion type

Characterization of Japanese-American men with a single neocortical AD lesion type

P2‐107: Intracranial Atherosclerosis as a contributing factor to Alzheimer's disease Dementia

Magnetic Resonance Imaging White Matter Hyperintensities and Brain Volume in the Prediction of Mild Cognitive Impairment and Dementia

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