These findings suggest that high intake of unsaturated fatty acids might protect against Parkinson disease.

Cerebral amyloid angiopathy is frequently found in demented and nondemented elderly persons, but its contribution to the causation of dementia is unknown. Therefore, we investigated the relation between the amount of cerebral amyloid angiopathy and the presence of dementia in 19 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. The advantage of studying hereditary cerebral hemorrhage in amyloidosis-Dutch type is that patients with this disease consistently have severe cerebral amyloid angiopathy with minimal neurofibrillary pathology. The amount of cerebral amyloid angiopathy, as quantified by computerized morphometry, was strongly associated with the presence of dementia independent of neurofibrillary pathology, plaque density, or age. The number of cortical amyloid beta-laden severely stenotic vessels, vessel-within-vessel configurations, and cerebral amyloid angiopathy-associated microvasculopathies was associated with the amount of cerebral amyloid angiopathy and dementia. A semiquantitative score, based on the number of amyloid beta-laden severely stenotic vessels, completely separated demented from nondemented patients. These results suggest that extensive (more than 15 amyloid beta-laden severely stenotic vessels in five frontal cortical sections) cerebral amyloid angiopathy alone is sufficient to cause dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type. This may have implications for clinicopathological correlations in Alzheimer's disease and other dementias with cerebral amyloid angiopathy.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of beta-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma. The disease is due to a point mutation at codon 693 of the amyloid precursor protein (beta PP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke. The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article.

Cerebral amyloid-beta (A beta) angiopathy is the histopathological hallmark of hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D). A beta deposits are found mainly in the cerebral and cerebellar meningocortical blood vessels and as plaques throughout the cerebrocortical gray matter. A beta deposition in arteries and arterioles starts at the junction of media and adventitia and proceeds to involve the media causing degeneration of the vascular smooth muscle cells. Cerebrocortical arterioles often show one or two layers of radial A beta around a layer of homogenous A beta that replaces the media. Degenerating neurites, reactive astrocytes and microglial cells may surround cerebrocortical angiopathic arterioles and capillaries, probably in reaction to invasion of the perivascular neuropil by A beta fibrils. Furthermore, clusters of coarse extracellular matrix deposits may be found near A beta-laden cerebrocortical arterioles. The amyloid-associated proteins, cystatin C, and beta PP colocalize diffusely with Dutch vascular A beta, whereas HLA-DR immunoreactivity is found only in the periphery of the diseased vessel wall. The latter phenomenon may be related to the presence of perivascular cells. Angiopathic blood vessels frequently show structural changes. The relation of the described pathology to the development of hemorrhage, infarction and leukoencephalopathy needs further elucidation.

Background: Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration. Methods: In a prospective population-based cohort study among 6,512 participants aged ≧55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption. Results: After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95–2.37). Conclusion: Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease.