Based on a combination of the clinical and pathological data, we suggest that microinfarcts in the cerebral cortex associated with severe CAA may be the primary pathological substrate in a significant proportion of VaD cases. Future studies should be undertaken to confirm or dismiss the hypothesis that these cases exhibit a different symptom profile than VaD cases without CAA.

No abstract

To test the hypothesis that the cerebral amyloid angiopathy (CAA) of Alzheimer’s disease (AD) is quantitatively associated with white matter lesions (WML), the brains of 63 demented patients exhibiting varying degrees of Alzheimer encephalopathy (AE) were examined, along with those of 10 nondemented control cases. The ratio of amyloid-positive to amyloid-negative vessels in the leptomeninges of the frontal pole from each patient was calculated subsequent to microscopical examination, and the severity of WML was graded according to previously published criteria. In AD cases without a significant component of vascular dementia, the level of CAA was found to correlate with the degree of WML diagnosed and graded by neuropathology. Neither age nor severity of AE correlated significantly with WML. There may be several reasons for the conflicting results of this study vis-à-vis earlier investigations; the roles played by different methods of staining, CAA quantitation and patient subgroup selection are also discussed.

Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.

AD and VaD exhibit such different profiles of organ and vascular damage as well as of hypertension and DM that they clearly point toward different pathogenic origin with low likelihood of shared risk factors.