Anticoagulant Therapy for Senile Dementia*

Ratner, Jack T.; Rosenberg, Gilbert; Kral, V. A.; Engelsmann, F.

doi:10.1111/j.1532-5415.1972.tb00758.x

Cited by 50 publications

(18 citation statements)

References 7 publications

(6 reference statements)

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“…Additional evidence supporting an important role for fibrin(ogen) and clot formation in AD are the positive results obtained with anticoagulant therapy for this disease (Ratner et al, 1972; Walsh et al, 1978). Although those studies were small, the anticoagulant treatment either stopped the deterioration or provoked an improvement of the disease (Walsh, 1996).…”

Section: Discussionmentioning

confidence: 88%

Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

Cortes‐Canteli

Paul

Norris

et al. 2010

Neuron

288

416

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Summary Alzheimer's disease (AD) is a neurodegenerative disorder in which vascular pathology plays an important role. Since the β-amyloid peptide (Aβ) is a critical factor in this disease, we examined its relationship to fibrin clot formation in AD. In vitro and in vivo experiments showed that fibrin clots formed in the presence of Aβ are structurally abnormal and resistant to degradation. Fibrin(ogen) was observed in blood vessels positive for amyloid in mouse and human AD samples, and intravital brain imaging of clot formation and dissolution revealed abnormal thrombosis and fibrinolysis in AD mice. Moreover, depletion of fibrinogen lessened cerebral amyloid angiopathy pathology and reduced cognitive impairment in AD mice. These experiments suggest that one important contribution of Aβ to AD is via its effects on fibrin clots, implicating fibrin(ogen) as a potential critical factor in this disease.

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Section: Discussionmentioning

confidence: 88%

Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

Cortes‐Canteli

Paul

Norris

et al. 2010

Neuron

288

416

View full text Add to dashboard Cite

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“…Aβ accumulation and Aβ-induced cytotoxicity were reduced [44] and spatial memory was improved [45] after treatment of AD mice with enoxaparin, a low molecular weight heparin. In human studies, placebo-treated dementia patients showed a significant deterioration in cognition, while warfarin-treated patients did not show any change in cognitive decline [46]. In addition, unregulated studies carried out several decades ago showed that the majority of dementia patients treated with warfarin presented with improved cognition compared to untreated patients [47, 48].…”

Section: Thrombotic/fibrinolytic System In Admentioning

confidence: 99%

Fibrinogen and Altered Hemostasis in Alzheimer's Disease

Cortes‐Canteli

Zamolodchikov

Ahn

et al. 2012

JAD

147

142

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Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaques, tau tangles, brain atrophy, and vascular pathology. Vascular defects include cerebrovascular dysfunction, decreased cerebral blood flow, and blood brain barrier (BBB) disruption, among others. Here, we review the evidence that links Aβ with the vascular pathology present in AD, with a specific focus on the hemostatic system and the clotting protein fibrinogen. Fibrinogen is normally found circulating in blood, but in AD it deposits with Aβ in the brain parenchyma and cerebral blood vessels. We found that Aβ and fibrin(ogen) interact, and their binding leads to increased fibrinogen aggregation, Aβ fibrillization, and the formation of degradation-resistant fibrin clots. Decreasing fibrinogen levels not only lessens cerebral amyloid angiopathy (CAA) and BBB permeability, but it also reduces microglial activation and improves cognitive performance in AD mouse models. Moreover, a prothrombotic state in AD is evidenced by increased clot formation, decreased fibrinolysis, and elevated levels of coagulation factors and activated platelets. Abnormal deposition and persistence of fibrin(ogen) in AD may result from Aβ-fibrin(ogen) binding and altered hemostasis and could thus contribute to Aβ deposition, decreased cerebral blood flow, exacerbated neuroinflammation, and eventual neurodegeneration. Blocking the interaction between fibrin(ogen) and Aβ may be a promising therapeutic target for AD.

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“…The double‐blind study of Ratner et al (14) involved a follow‐up period of one year. They found that anticoagulant therapy could prevent brain deterioration in cerebrovascular insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Presenile Dementia: Further Experience with an Anticoagulant‐Psychotherapy Regimen*

Walsh

Walsh²

1974

J American Geriatrics Society

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The principles of an anticoagulant-psychotherapy regimen for presenile dementia are discussed. Short histories are given of 10 patients (including one with Huntington's chorea as well as dementia) who responded well to this treatment. It is important to keep the blood prothrombin time at 2.0-2.5 times the control time. The earlier treatment is started, the better the result. Even in cases in which there is n o significant improvement, the prevention of further deterioration is of great value. If properly controlled, this regimen is relatively safe and can maintain or improve the quality of life for dementia patients. When brain deterioration is observed in patients past the age of 70, it is usually accepted as an unfortunate manifestation associated with the aging process. However, when observed in patients of the 40-60 age group, it is one of the most puzzling problems in medicine. Traditionally, age 6 5 is arbitrarily chosen as the dividing line for nomenclature: after that age the brain deterioration is called senile dementia; before that age it is called presenile dementia. It is our hypothesis that they both represent variations of cerebrovascular insufficiency, regardless of age. This paper concerns our recent experience with a therapeutic regimen developed during the past eleven years. Ten patients have responded favorably to this treatment in such a way as to refute the general belief that presenile dementia is an irreversible disorder with a steady downhill course.Nineteen years of general practice have afforded the writer ample opportunity for ob-

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Anticoagulant Therapy for Senile Dementia*

Cited by 50 publications

References 7 publications

Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

Fibrinogen and Altered Hemostasis in Alzheimer's Disease

Presenile Dementia: Further Experience with an Anticoagulant‐Psychotherapy Regimen*

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