Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including anemia, dementia, hypertension, lymphoma, retinopathy, seizures, and neurodevelopmental disorders.A study by Yale University researchers (published in the February 12, 2004, issue of the New England Journal of Medicine) explored the role of mitochondria in insulin resistance among the offspring of patients with type 2 diabetes. Other studies have shown that the mechanism may involve the interruption of the mitochondrial signaling process in body cells (intramyocellular lipids). A study conducted at the Pennington Biomedical Research Center in Baton Rouge, Louisiana showed that this, in turn, partially disables the genes that produce mitochondria. Mechanisms
The effective overall energy unit for the available body energy is referred to as the daily glycogen generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. This value is slow to change in a given individual, as it takes between 18 and 24 months to complete a full cycle.The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the mitochondria in all of the cells of the human body; however, the relation between the energy generated by the mitochondria and the glycogen capacity is very loose and is mediated by many biochemical pathways. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable.
Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in magnetic resonance imaging of the brain in patients with Alzheimers disease. ARIA is associated with amyloid-modifying therapies, particularly human monoclonal antibodies such as aducanumab. There are two types of ARIA: ARIA-E and ARIA-H. The phenomenon was first seen in trials of bapineuzumab. ARIA-E
ARIA-E refers to cerebral edema, involving the breakdown of the tight endothelial junctions of the blood-brain barrier and subsequent accumulation of fluid. In a double-blind trial of the humanised monoclonal antibody solanezumab (n = 2042), sixteen patients (11 taking the drug, 5 taking a placebo), or 0.78% developed ARIA-E. A further 7 patients developed ARIA-E during an open-label extension of the trial.The effect of ARIA-E depends on the severity and location of the edema. Symptoms may include headache, changes in mental state, confusion, vomiting, nausea, tremor and gait disturbances. ARIA-H
ARIA-H refers to cerebral microhaemorrhages (mH), small haemorrhages on the brain, often accompanied by hemosiderosis. mH are usually seen as small, round and low intensity lesions and are small haemosiderin deposits. Some studies define mH as being less than or equal to 10mm, while others define the cut-off as ≤ 5mm. The prevalence of mH in healthy elderly people is approximately 6%, but this value increases to between 50% and 80% in elderly people with cerebrovascular disease. ARIA MRI Classification Criteria
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