RESUMO
Alzheimer's disease is the most common major neurocognitive disorder with substantial social and economic impacts. This article is an update on current pharmacotherapy, advancements in biomarker use, and drugs in the pipeline for this disease. To date, no new drug has qualified to be added to the current therapeutic arsenal comprising cholinesterase inhibitors and the NMDA receptor antagonist memantine. Drugs in the pipeline include symptomatic therapies that are neurotransmitter-based, but mostly disease-modifying therapies. The latter have yielded disappointing results by focusing mainly on the two pathophysiological hallmarks of Alzheimer's disease: Aß amyloid deposits and tau protein aggregates forming neurofibrillary tangles. These unsuccessful trials may have resulted from studying these drugs 'too late' relative to Alzheimer's disease onset, in addition to focusing only on the amyloid cascade. In fact, Alzheimer's disease is a complex multifactorial disease. Combining different biomarkers might enhance our ability to identify those patients most at risk of developing the disease, and better predict their conversion rates. Furthermore, adopting an integrative treatment approach by targeting additional pathophysiological pathways in Alzheimer's disease such as inflammation and oxidative stress could be the key to better outcomes in Alzheimer's disease pharmacotherapy research.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Humanos , Terapia de Alvo Molecular , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
This study examined the effects of intensive voice treatment (the Lee Silverman Voice Treatment [LSVT]) on ataxic dysarthria in a woman with cerebellar dysfunction secondary to thiamine deficiency. Perceptual and acoustic measures were made on speech samples recorded just before the LSVT program was administered, immediately after it was administered, and at 9 months follow-up. Results indicate short- and long-term improvement in phonatory and articulatory functions, speech intelligibility, and overall communication and job-related activity following LSVT. This study's findings provide initial support for the application of LSVT to the treatment of speech disorders accompanying ataxic dysarthria. Potential neural mechanisms that may underlie the effects of loud phonation and LSVT are addressed.