Cognitive Disorders and Dementia

Early changes in language are associated with neurodegenerative dementias such as Alzheimer’s disease and frontotemporal dementia, as well as other neuropsychiatric conditions. Such changes may well precede other clinical signs of neurodegeneration, and analysis of language (computational neurolinguistics) may provide early markers to detect specific patterns of change that can be associated with particular dementias, as shown by the analysis of the writing of Iris Murdoch by Prof Peter Garrard. This seminal work has been further developed and a multilingual (currently English, Italian and Spanish) research project by a worldwide network of collaborators is developing a standardised assessment of language as an aid to help early diagnosis of dementias.

City St George's, School of Health & Medical Sciences (Tooting) is a leading centre for research in brain microvascular disease, the main cause of vascular dementia. Disease that affects the small blood vessels of the brain lead to extensive damage, observed by MRI as high signal intensity (see figure A below). Histopathological analysis shows concentric fibrosis (green) in the walls of small penetrating arteries in the brain of an older person (see figure B below) indicative of small vessel disease. We are leading a phase II clinical trial, PASTIS, of the Viagra-like drug Tadalafil, for possible use as a potential treatment to improve brain blood flow in such dementias.

Other work involves looking for biomarkers of the inflammatory and brain repair pathways to better understand how we can improve treatments for patients with brain haemorrhage.

Bleeding into the brain (also called intracranial haemorrhage, ICH) happens in 10% to 15% of all strokes. When this happens, the chances of dying or being disabled are much higher than a stroke caused by a blood clot into a blood brain vessel (an ischaemic stroke). ICH is a medical emergency because of the high risk of brain injury and cell death. In certain situations surgery may be a treatment option. If done quickly, the blood mass in the brain (haematoma) can be reduced, which reduces inflammation and brain swelling. This can potentially reduce cell death, but to date the overall benefit appears limited.

While clinical trials have explored the role of surgical removal of the blood mass and/or dissolving it, the reaction of the brain while trying to resolve the blood mass and repair the damage is still unclear. Animal studies have shown activation of not only an inflammation process but also an anti-inflammation (repair) process following ICH. If the anti-inflammation process is activated in humans, ICH can be better treated. In our studies, we are investigating the inflammatory and anti-inflammatory responses after ICH in donated human brain tissue samples and measuring the related biomarkers in the blood and cerebrospinal fluid to help understand how the human brain repairs itself and absorbs the haematoma. Our results may guide future studies and/or treatment approaches to treat ICHs.

Figure A is a computed tomography cut of the brain showing an intraparenchymal haemorrhage (arrow). Figure B is a post-mortem picture showing the haemorrhage (arrow) and the inflamed area (arrow heads). Figure C shows activated inflammatory brain cells called microglia (arrows).