However, a more recent prospective study published in 2008 with a cohort of 591 people showed a statistically significant difference between patients with antibodies indicating recent reactivation of HSV and those without these antibodies in the incidence of Alzheimers disease, without direct correlation to the APOE-epsilon4 allele.The trial had a small sample of patients who did not have the antibody at baseline, so the results should be viewed as highly uncertain. In 2011, Manchester University scientists showed that treating HSV1-infected cells with antiviral agents decreased the accumulation of β-amyloid and tau protein and also decreased HSV-1 replication.A 2018 retrospective study from Taiwan on 33,000 patients found that being infected with herpes simplex virus increased the risk of dementia 2.56 times (95% CI: 2.3-2.8) in patients not receiving anti-herpetic medications (2.6 times for HSV-1 infections  and 2.0 times for HSV-2 infections). However, HSV-infected patients who were receiving anti-herpetic medications (acyclovir, famciclovir, ganciclovir, idoxuridine, penciclovir, tromantadine, valaciclovir, or valganciclovir) showed no elevated risk of dementia compared to patients uninfected with HSV. Multiplicity reactivation
Multiplicity reactivation (MR) is the process by which viral genomes containing inactivating damage interact within an infected cell to form a viable viral genome. MR was originally discovered with the bacterial virus bacteriophage T4, but was subsequently also found with pathogenic viruses including influenza virus, HIV-1, adenovirus simian virus 40, vaccinia virus, reovirus, poliovirus and herpes simplex virus.When HSV particles are exposed to doses of a DNA damaging agent that would be lethal in single infections, but are then allowed to undergo multiple infection (i.e.
CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19. The disease belongs to a family of disorders called the leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.The condition was identified and named by French researchers Marie-Germaine Bousser and Elisabeth Tournier-Lasserve in the 1990s. Together with two other researchers, Hugues Chabriat and Anne Joutel, they received the 2019 Brain Prize for their research into the condition. Signs and symptoms
CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 and 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.Ischemic strokes are the most frequent presentation of CADASIL, with approximately 85% of symptomatic individuals developing transient ischemic attacks or stroke(s). The mean age of onset of ischemic episodes is approximately 46 years (range 30–70). A classic lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. It is worthy of note that ischemic strokes typically occur in the absence of traditional cardiovascular risk factors.