It is known that watershed cortical areas are the first to be deprived of sufficient blood flow in the event of cerebral hypoperfusion, which are frequently sites of cortical microinfarcts. Cerebral hypoperfusion occurs in both, AD and neurospirochetoses (Hachinski and Munoz, 1997, Logigian, 1997).

Rosenbaum et al., (1942) have observed cerebral hypoperfusion in general paretic patients suffering from dementiamore than fifty years ago. Cerebral blood vessels are also severely involved in late or chronic neurosyphilis. In dementia paralytica the smaller arteries and particularly the capillaries show marked pathological changes, while in meningovascular syphilis, chiefly, the medium-size and larger arteries are affected (Scheinker, 1938).

Recent observations showed that cerebral perfusion was also significantly decreased in Lyme patients with neuropsychiatric symptoms compared to normal subjects (Logigian, 1997, 1999; Newberg et al., 1999; Fallon et al., 2003).

Increased cerebral blood flow and improved clinical symptoms were observed following antibiotic treatment in these late or chronic neurospirochetoses  (e.g. Patterson et al., 1950; Logigian et al., 1997, 1999).

Despite the established association between Alzheimer disease and cerebral hypoperfusion, information regarding the occurrence of watershed cortical microinfarcts is lacking, despite that such cortical infarcts may further increase the severity of cognitive decline in Alzheimer disease.
Accordingly, in the next study, in collaboration with Oda Suter from the University Institute of Pathology, Lausanne, Switzerland and Rudolph Kraftsik from the Institute of Cellular Biology and Morphology, University of Lausanne, Switzerland, we have analyzed whether cortical microinfarcts and disturbed cortical capillary network may also occur in Alzheimer disease (Suter et al., 2002). The brains of 184 autopsy cases (105 definite Alzheimer cases and 79 age-matched controls without any cortical lesions) were selected and were analyzed by histochemical and immunohistochemical techniques. Three-dimensional reconstruction (3-D) of the whole cerebrum, using 3 mm spaced serial sections, was also performed in 6 Alzheimer cases in order to study the intra-hemispheric and inter-hemispheric distribution of watershed cortical microinfarcts (Suter et al., 2002).

3-D reconstruction of whole AD brains showing that the cortical microinfarcts are restricted to the watershed cortical areas (Suter et al. 2002)

The results showed a significant association between the frequency of watershed cortical infarcts and Alzheimer disease. The frequency was almost 13 times higher in Alzheimer's disease  (32.4%) compared to controls (2.5%). The 3-D reconstruction of their intra- and inter-hemispheric distributions showed that they are clearly restricted to the watershed cortical zones concluding, that cerebral hypoperfusion is the determinant factor in their genesis (Suter et al., 2002). Congophilic angiopathy is an important risk factor of watershed cortical infarcts. In Alzheimer patients with congophilic angiopathy 60% exhibited cortical watershed micro-infarcts.  

Severe disturbation of cortical capillary network in Alzheimer's disease (Suter et al., 2002)

The results concluded that cerebral hypoperfusion induces not only white matter changes in Alzheimer disease, but cortical watershed microinfarcts as well. These microinfarcts may further aggravate the degenerative process and worsen dementia in Alzheiemr disease. For their prevention, to monitor blood pressure and treat arterial hypotension is essential, particularly as neuroleptic and sedative drugs, which decrease blood pressure,are frequently employed in the treatment of Alzheimer disease (Suter et al., 2002).

In the other type of vascular lesion in the meningovascular form of late neurosyphilis and Lyme neuroborreliosis, the parenchymal involvement is secondary to the inflammatory damage of  leptomeningeal arteries with consequent cerebral vascular infarcts (Miklossy et al., 1990).  Their localization, distribution and size differ from the watershed cortical infarcts.

These observations may also give a comprehensive explanation why in neurospirochetoses and in AD cortical atrophy, leading to dementia is frequently associated with vascular infarcts.