digoxin and Dementia

Topics: Antihypertensive Agents; Cardiotonic Agents; Clonidine; Dementia; Digitoxin; Digoxin; Half-Life; Humans; Methyldopa; Propranolol; Reserpine

Alternative splicing has emerged as a promising therapeutic target in a number of human disorders. However, the discovery of compounds that target the splicing reaction has been hindered by the lack of suitable high-throughput screening assays. Conversely, the effects of known drugs on the splicing reaction are mostly unclear and not routinely assessed. We have developed a two-color fluorescent reporter for cellular assays of exon inclusion that can accommodate nearly any cassette exon and minimizes interfering effects from changes in transcription and translation. We used microtubule-associated protein tau (MAPT) exon 10, whose missplicing causes frontotemporal dementia, to test the reporter in screening libraries of known bioactive compounds. These screens yielded several compounds that alter the splicing of the exon, both in the reporter and in the endogenous MAPT mRNA. One compound, digoxin, has long been used in the treatment of heart failure, but was not known to modulate splicing. The positive compounds target different signal transduction pathways, and microarray analysis shows that each compound affects the splicing of a different set of exons in addition to MAPT exon 10. Our results identify currently prescribed cardiotonic steroids as modulators of alternative splicing and demonstrate the feasibility of screening for drugs that alter exon inclusion.

Topics: Alternative Splicing; Cardiotonic Agents; Cell Line; Dementia; Digoxin; Drug Evaluation, Preclinical; Exons; Gene Expression Profiling; Genes, Reporter; Heart Failure; Humans; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Signal Transduction; tau Proteins

Topics: Atrial Fibrillation; Cognition Disorders; Dementia; Digoxin; France; Humans

Cognitive impairment or clinical signs of dementia in an old patient who receives digoxin, should suggest a digitalis intoxication. Symptoms can be present although a normal digoxin serum concentration. It is recommended to stop the treatment to obtain a regression of dementia symptoms.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Cognition Disorders; Dementia; Digoxin; Female; Humans

To document the presence and treatment of selected vascular risk factors in patients with vascular cognitive impairment and elements affecting undertreatment of vascular risk factors.. Secondary analysis of the Canadian Study of Health and Aging database, which is a national, representative, cross-sectional study of the epidemiologic distribution of dementia in elderly people in Canada.. Survey.. Institutionalized and community-dwelling elderly people.. Vascular risk factors, dementia diagnosed by standard methods, and medication use.. Treatable vascular risk factors occurred significantly more often in patients with vascular cognitive impairment (with and without dementia) than in patients with probable Alzheimer disease or normal cognitive function. For example, 76% of patients with vascular dementia and 57% of those with vascular cognitive impairment without dementia had a history of stroke, compared with only 5% of those with probable Alzheimer disease and 7% of those with no cognitive loss. (For hypertension, the comparable figures are 55%, 48%, 24%, and 38%, respectively.) Potential undertreatment of vascular risk factors had little effect on mean control of vascular risk factors. For example, the mean (+/- SD) systolic blood pressure in those being treated was 144 +/- 26 mm Hg, compared with 142 +/- 25 mm Hg in those not receiving pharmacological treatment. In each group (treated vs untreated), the proportion of patients with a systolic blood pressure higher than 160 mm Hg was 20% and 16%, respectively. Potential undertreatment occurred most often in those with severe dementia and those living in nursing homes.. Vascular risk factors occurred more commonly in patients with vascular cognitive impairment compared with other patients, including those with other forms of dementia. When present, such risk factors were often treated pharmacologically, except in patients with severe dementia and those in long-term care institutions. Undertreatment does not, in general, result in worsened risk factor control.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aspirin; Cognition Disorders; Dementia; Diabetes Complications; Diabetes Mellitus; Digoxin; Female; Humans; Hypertension; Male; Risk Factors; Vascular Diseases

Topics: Aged; Brain; Central Nervous System; Confusion; Dementia; Diagnosis, Differential; Digoxin; Geriatric Psychiatry; Humans; Kinetics; Patient Care Team