Neuropathological Indexes of Alzheimer's Disease in Demented and Nondemented Persons Aged 80 Years and Older

Berg, Leonard van den; Dw, McKeel; Jp, Miller; Baty, Jack; Jc, Morris

doi:10.1001/archneur.1993.00540040011008

Cited by 244 publications

(119 citation statements)

References 58 publications

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“…Previous studies showed little or no correlation between the quantity of Ab deposition and behavioral deficits (Terry et al, 1991;Arriagada et al, 1992;Berg et al, 1993;Westerman et al, 2002;Van Dam et al, 2003) in both humans with AD and animal models of AD. Increasing evidence has indicated that soluble amyloid oligomers may be directly toxic to neuronal structure and function (Gong et al, 2003;Watson et al, 2005;Lacor et al, 2007;Shankar et al, 2007).…”

Section: Discussionmentioning

confidence: 97%

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Dong

Yuede

Coughlan

et al. 2008

Neuropsychopharmacol

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Memantine, an uncompetitive NMDA receptor antagonist used for the treatment of Alzheimer's disease (AD), has been hypothesized to have neuroprotective properties. However, the similarity of its mechanism of action to other NMDA receptor antagonists has led to concerns that it may also have neurotoxic effects. To assess both the neuroprotective and neurotoxic potential of memantine in a mouse model of AD (Tg2576 mice), we used quantitative light and electron microscopy to investigate the effects of long-term (6 months) administration of memantine (5, 10 and 20 mg/kg) on plaque deposition and neuronal morphology in the hippocampus and overlying cortex. A fear-conditioning paradigm was used to evaluate the behavioral consequences of any observed changes in structure. Administration of the two higher doses of memantine (10 and 20 mg/kg) was associated with a significant decrease in b-amyloid (Ab) plaque deposition, increases in synaptic density and the appearance of degenerating axons; the latter two effects were independent of genotype. Administration of the lowest dose of memantine (5 mg/kg) was associated with a significant decrease in Ab plaque deposition and a significant increase in synaptic density, but not a significant increase in degenerating axons. However, memantine did not significantly improve behavioral deficits associated with genotype in a fear-conditioning paradigm at any dose. These results suggest that chronic memantine administration may have both neuroprotective and neurotoxic effects in a mouse model of AD.

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Section: Discussionmentioning

confidence: 97%

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Dong

Yuede

Coughlan

et al. 2008

Neuropsychopharmacol

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“…Initiated in 1979, a total of 2,716 individuals have been enrolled and 842 have come to autopsy. 21,22 Demographic data and diagnoses at expiration are reported in tables 1 and 2. The pure and mixed DLB samples included all available cases.…”

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confidence: 99%

“…Experienced clinicians conducted independent semistructured interviews with the participant and a knowledgeable collateral source at the initial visit and annually thereafter. The Clinical Dementia Rating (CDR), 21,22,25 was used to determine the presence or absence of dementia and, if present, stage its severity. 26 The CDR rates cognitive function in each of six categories (memory, orientation, judgment, problem solving, performance in community affairs, and home and hobbies and personal care).…”

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confidence: 99%

“…3 The CDR has been validated in studies of all forms of dementia, is sensitive to clinical progression, and correlates highly with autopsy-confirmed AD. 22,26,29 The criteria used to diagnose DLB have been evolving since the inception of the McKeith criteria, and many of the participants with pure DLB and DLB/AD enrolled in the current study before their implementation. As a result, diagnostic criteria for AD has been historically more accurate and prevalent, as shown in table 2.…”

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confidence: 99%

“…All brains were examined with a standard protocol. 22,38 Following fixation in neutral buffered 10% formalin, tissue blocks were taken from 30 brain regions. Sections (6 m) from paraffin-embedded tissue blocks were stained with hematoxylin-eosin, Gallyas, and modified Bielchowsky silver stains and immunohistochemical methods.…”

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confidence: 99%

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Verbal and visuospatial deficits in dementia with Lewy bodies

2005

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Abstract-Objective:To investigate the cognitive decline in dementia with Lewy bodies (DLBs) and characterize the contribution of Lewy bodies (LBs) to cognitive impairment in the presence of concurrent Alzheimer disease (AD). Methods: Cognitive deficits and rates of progression attributable to DLB and AD neuropathology were investigated in three groups of participants from the longitudinal cohort of the Alzheimer Disease Research Center at Washington University with autopsy-confirmed diagnoses of pure DLB (n ϭ 9), mixed DLB/AD (n ϭ 57), and pure AD (n ϭ 66). Factor analysis was used to recover latent constructs in a comprehensive psychometric test battery, analysis of variance was used to test group differences on the observed dimensions, and random effects models were used to test longitudinal rates of cognitive decline. Results: Patients with AD pathology performed worse on the verbal memory dimension. Patients with LB pathology performed worse on the visuospatial dimension. Combined pathology affected visuospatial performance but not verbal memory. The rate of cognitive decline in the DLB, DLB/AD combined, and the pure AD groups was equivalent. Conclusions: The comorbid presence of DLB and AD alters the cognitive presentation of visuospatial deficits in dementia but does not alter dementia progression. Both visuospatial and verbal abilities declined at similar rates across the three patient groups. DLB diagnosis may be improved, particularly when there is comorbid AD, by using domain-specific testing. NEUROLOGY 2005;65:1232-1238 In contrast to the neuritic plaques and neurofibrillary tangles of Alzheimer disease (AD), dementia with Lewy bodies (DLB) is characterized by ␣-synuclein inclusions (i.e., Lewy bodies [LBs]) in neocortical, limbic, and subcortical regions. DLB and associated disorders of ␣-synuclein aggregation (synucleinopathies) are the second most common cause of neurodegenerative dementia after AD.1 Although a minority of DLB cases have only LBs at autopsy ("pure" DLB), the more common finding is a mixture of LBs with sufficient burden of neuritic plaques and neurofibrillary tangles to also diagnose AD (mixed DLB/AD). The reverse is also true, as LBs are observed frequently in AD. A review of autopsied cases from the Washington University Alzheimer Disease Research Center (ADRC) suggests that as many as 25% of autopsied AD cases have cortical/ limbic LBs in sufficient quantity to be classified as mixed DLB/AD, although most did not clinically manifest the distinctive symptoms of DLB.2,3 Other autopsy series confirm the high co-occurrence of DLB and AD. 4,5 Although there are published criteria for the clinical features of DLB, 3 these criteria appear to best capture the "pure" DLB cases. It is unclear how well the criteria capture the more common mixed DLB/AD group, many of whom may be misclassified clinically as probable AD.1 Diagnostic criteria for DLB include progressive cognitive decline plus at least two of the following: parkinsonism, visual hallucinations, or cognitive fluctuation. 3 Becaus...

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Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease

Bierer

Hof²,

Purohit³

et al. 1995

Archives of Neurology

458

240

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Neuropathological Indexes of Alzheimer's Disease in Demented and Nondemented Persons Aged 80 Years and Older

Cited by 244 publications

References 58 publications

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Verbal and visuospatial deficits in dementia with Lewy bodies

Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease

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