Cerebral microvascular pathology in aging and Alzheimer's disease

The aging of the central nervous system and the development of incapacitati ng neurological diseases like Alzheimer's disease (AD) are generally associ ated with a wide range of histological and pathophysiological changes event ually leading to compromised cognitive status. Although the diverse trigger s of the neurodegenerative processes and their interactions are still the t opic of extensive debate, the possible contribution of cerebrovascular defi ciencies has been vigorously promoted in recent years. Various forms of cer ebrovascular insufficiency such as reduced blood supply to the brain or dis rupted microvascular integrity in cortical regions may occupy an initiating or intermediate position in the chain of events ending with cognitive fail ure. When, for example, vasoconstriction lakes over a dominating role in th e cerebral vessels, the perfusion rate of the brain can considerably decrea se causing directly or through structural vascular damage a drop in cerebra l glucose utilization. Consequently, cerebral metabolism can suffer a setba ck leading to neuronal damage and a concomitant suboptimal cognitive capaci ty. The present review focuses on the microvascular aspects of neurodegener ative processes in aging and AD with special attention to cerebral blood fl ow, neural metabolic changes and the abnormalities in microvascular ultrast ructure. In this context, a few of the specific triggers leading to the pro minent cerebrovascular pathology, as well as the potential neurological out come of the compromised cerebral microvascular system are also going to be touched upon to a certain extent, without aiming at total comprehensiveness . Finally, a set of animal models are going to be presented that are freque ntly used to uncover the functional relationship between cerebrovascular fa ctors and the damage to neural networks. (C) 2001 Elsevier Science Ltd. All rights reserved.