Method of obtaining an indication of an efficacy of a drug
Methods of assessing or obtaining an indication of the presence of a cognitive disorder by analysing microstructural changes in regions of the brain are provided. The invention particularly relates to methods of assessing or obtaining an indication of the presence of types of dementia, for example Alzheimer's disease, by analysing changes in minicolumns in regions or layers of the cortex of the brain or of the whole brain.
1 . A computer-implemented method of obtaining an indication of an efficacy of a drug which is being used to treat a cognitive disorder in a subject, the method comprising the steps of:
determining at least one first diffusion Magnetic Resonance Imaging (MRI) measurement of one or more minicolumn-based parameters obtained from cortical grey matter in a brain of the subject;
determining at least one second diffusion MRI measurement of one or more minicolumn-based parameters obtained from the cortical grey matter in the brain of the subject, wherein:
the minicolumn-based parameters are one or more parameters selected from a group consisting of minicolumn width, minicolumn spacing, axonal fibre bundle width, axonal fibre bundle spacing, dendritic fibre bundle width, dendritic fibre bundle spacing, minicolumn core width, and minicolumn peripheral neuropil space,
the at least one first diffusion MRI measurement or at least one second diffusion MRI measurement is perpendicular diffusivity, mean minicolumn diffusivity, radial diffusivity, minicolumn width, fractional anisotropy, grey matter density or angle of columnar deviation;
the drug is administered to the subject in an interval between taking of the first and second diffusion MRI measurements,
if the first diffusion MRI measurement is positively correlated or proportional to a severity of the cognitive disorder or a trait of said disorder, an increase in the second diffusion MRI measurement compared to the first diffusion MRI measurement is indicative of a lack of efficacy of the drug, and a decrease in the second diffusion MRI measurement compared to the first diffusion MRI measurement is indicative of the efficacy of the drug, and
if the first diffusion MRI measurement is negatively correlated or inversely proportional to the severity of the cognitive disorder or a trait of said disorder, an increase in the second diffusion MRI measurement compared to the first diffusion MRI measurement is indicative of the efficacy of the drug, and a decrease in the second diffusion MRI measurement compared to the first diffusion MRI measurement is indicative of the lack of efficacy of the drug.
2 . The method as claimed in claim 1 , wherein the cognitive disorder is a mental health disorder that affects learning, memory, perception and/or problem solving.
3 . The method as claimed in claim 1 , wherein the cognitive disorder is a form of dementia.
4 . The method as claimed in claim 1 , wherein the at least one first diffusion MRI measurement of one or more minicolumn-based parameters or the at least one second diffusion MRI measurement of one or more minicolumn-based parameters are obtained from one or more different regions of the brain, preferably two or more, three or more, four or more, five or more, six or more, seven or more, or eight or more different regions of the brain, most preferably five or more different regions of the brain, or from the whole brain.
5 . The method as claimed in claim 1 , wherein the at least one first diffusion MRI measurement of one or more minicolumn-based parameters or the at least one second diffusion MRI measurement of one or more minicolumn-based parameters are obtained from or derived from one or more regions or layers of a cortex of the brain, preferably from a cortical layer or cortical layers.
6 . The method as claimed in claim 1 , wherein the at least one first diffusion MRI measurement of one or more minicolumn-based parameters or the at least one second diffusion MRI measurement of one or more minicolumn-based parameters are obtained from or derived from one or more brain regions selected from the group consisting of parahippocampal gyrus, fusiform gyrus, dorsolateral prefrontal cortex area, Heschl's gyrus, planum temporale, inferior parietal lobule, middle temporal gyrus, a primary visual cortex, an orbitofrontal cortex and a primary motor cortex.
7 . The method as claimed in claim 1 , wherein the cognitive disorder is Alzheimer's Disease (AD) and wherein the at least one first diffusion MRI measurement of one or more minicolumn-based parameters or the at least one second diffusion MRI measurement of one or more minicolumn-based parameters are obtained from or derived from one or more brain regions selected from the group consisting of:
(i) banks of a superior temporal sulcus, entorhinal, isthmus cingulate, lateral occipital, lateral oribitofrontal, middle temporal, parahippocampal, parstriangularis, pericalcarine or posterior cingulate region of a left-hand cortex; and
(ii) the banks of the superior temporal sulcus, cuneus, entorhinal, middle temporal, parahippocampal, paracentral or posterior cingulate region of a right-hand cortex.
8 . The method as claimed in claim 1 , wherein the cognitive disorder is Alzheimer's Disease (AD) and wherein the at least one first diffusion MRI measurement of one or more minicolumn-based parameters or the at least one second diffusion MRI measurement of one or more minicolumn-based parameters are obtained from or derived from the whole brain.
9 . A system or apparatus comprising at least one processing means arranged to carry out the steps of a method as claimed in claim 1 .