Alzheimer's Disease – Top USMLE Diseases

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance, as well as relative insulin deficiency. Genetically determined causes of diabetes (e.g., maturity-onset diabetes of the young and late autoimmune diabetes in adults) are being increasingly recognized, but they make up a small portion of cases. There is no definitive cure for DM. The objective of management is the prevention of complications, which may include coronary artery disease, CKD, retinopathy, and neuropathy. Long-term monitoring and maintenance of optimal blood glucose levels are key to preventing complications. Treatment is specific to the type of diabetes, with glycemic control as the goal in all types; insulin replacement is essential in type 1, and a healthy diet, lifestyle changes, and medications are important in type 2.

Wernicke encephalopathy is an acute, reversible, neurologic condition that arises because of a severe deficiency of thiamine (vitamin B1). This condition is most commonly seen in people with excessive alcohol use. The classic triad of symptoms is encephalopathy, oculomotor dysfunction, and gait ataxia, although all 3 features are only present in ⅓ of patients. Korsakoff syndrome is a severe and late neuropsychiatric manifestation of Wernicke encephalopathy. Korsakoff syndrome presents with personality changes, anterograde and retrograde amnesia, and confabulation. Some of these changes are irreversible. Both Wernicke encephalopathy and Korsakoff syndrome may be diagnosed clinically. Treatment includes absolute abstinence from alcohol and thiamine supplementation.

Gregor Mendel (1822–1884), the "father of genetics", was an Augustine monk and mathematician who performed cross-breeding experiments with peas and beans from a monastery garden. Based on the experiments, Mendel deduced hereditary factors may be passed from the parental generation to the filial generation. From the deductions, the father of genetics formed Mendel's laws of heredity: the law of segregation, the law of independent assortment, and the law of dominance. Mendel's laws described the inheritance of uncoupled autosomal genes based on statistical predictions. The gene traits follow the laws of mendelian inheritance.

Cholinomimetic drugs, also known as parasympathomimetics or cholinergic agonists, increase acetylcholine (ACh), which acts on cholinergic muscarinic and nicotinic receptors. Other cholinomimetic drugs result in a net cholinergic effect by inhibiting the cholinesterase enzyme. Muscarinic receptors are found in the CNS and are part of the parasympathetic nervous system, which responds to cholinomimetics. Nicotinic receptors are found in the CNS at the neuromuscular junction. Physiologic effects on muscarinic receptors include bronchoconstriction, lacrimation, and bradycardia. Physiologic effects on nicotinic receptors include vasoconstriction, tachycardia, and elevated blood pressure. Cholinergic activation of muscarinic receptors on vascular endothelial cells cause an increase in nitric oxide, which diffuses to the adjacent vascular smooth muscle cells, resulting in smooth muscle relaxation/vasodilation and a paradoxical effect of the cholinomimetics on bronchial smooth muscle (constriction) and vascular smooth muscle (relaxation). Clinical uses of cholinomimetic agents include treatment of dementia, glaucoma, and as an aid for smoking cessation. The primary adverse effect of cholinergic drugs is overstimulation of the parasympathetic nervous system. Symptoms result from excessive levels of ACh in synapses, glands, smooth muscles, and motor endplates.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of

Major neurocognitive disorders (NCDs), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. There are several distinct etiologies for major NCDs. While there are known risk factors and measures to prevent major NCDs, there are no effective curative treatments.

Population genetics is a field in genetics that is concerned with the differences in the gene pool between different populations and how this underlies phenotypic differences between populations. The Hardy-Weinberg equilibrium serves as a basis for studying genetic variation within a population and allows for the calculation of allelic frequency. The process of natural selection is what determines the allelic frequencies in the population and the variability in the genotype-phenotype relationships between species.

Wernicke encephalopathy is an acute, reversible condition that is caused by severe thiamine deficiency. This condition is most commonly seen in alcohol abusers. The classic triad of symptoms is encephalopathy, oculomotor dysfunction, and gait ataxia, although all 3 features are only present in one-third of patients. Korsakoff syndrome is a severe and late neuropsychiatric manifestation of Wernicke encephalopathy. Korsakoff syndrome presents with personality changes, anterograde and retrograde amnesia, and confabulation. Some of these changes are irreversible. Both Wernicke encephalopathy and Korsakoff syndrome may be diagnosed clinically. Treatment includes absolute abstinence from alcohol and thiamine supplementation.

As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Several genetic defects and risk factors have been described, although there is no clear cause in the majority of cases. The main pathologic features are neuritic plaques, extracellular deposits of amyloid peptides, and neurofibrillary tangles. The clinical features are memory impairment, loss of executive function and judgment, impaired cognitive function, and behavioral changes. Diagnosis is based on clinical examination, neuropsychiatric testing, and imaging. There is no curative therapy, but symptomatic management with medications may slow progression; these include cholinesterase inhibitors, the N-methyl-D-aspartate (NMDA) receptor antagonist memantine, and a recently approved anti-amyloid monoclonal antibody.