Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.

Laboratory of Neuroscience (LIM 27) Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 - São Paulo, SP, Brazil. .
The British journal of psychiatry: the journal of mental science (Impact Factor: 6.62). 05/2011; 198(5):351-6. DOI: 10.1192/bjp.bp.110.080044
Source: PubMed

ABSTRACT Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.
To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).
Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.
Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.
The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the search for therapeutic modifiers, frontotemporal dementia (FTD) has traditionally been overshadowed by other conditions such as Alzheimer's disease (AD). A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic variants in familial and sporadic forms of disease and the identification of TAR DNA binding protein of 43 kDa (TDP-43) as the defining constituent of inclusions in more than half of cases. In combination with an ever-expanding knowledge of the function and dysfunction of tau—a protein which is pathologically aggregated in the majority of the remaining cases—there exists a greater understanding of FTD than ever before. These advances may indicate potential approaches for the development of hypothetical therapeutics, but FTD remains highly complex and the roles of tau and TDP-43 in neurodegeneration are still wholly unclear. Here the challenges facing potential therapeutic strategies are discussed, which include sufficiently accurate disease diagnosis and sophisticated technology to deliver effective therapies.
    Frontiers in Aging Neuroscience 08/2014; · 2.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) is involved in a broad range of cellular processes including cell proliferation, apoptosis and inflammation. It is now also increasingly acknowledged as having a role to play in cognitive-related processes such as neurogenesis, synaptic plasticity and neural cell survival. Cognitive impairment represents a major debilitating feature of many neurodegenerative and psychiatric disorders, including Alzheimer's disease, mood disorders, schizophrenia and fragile X syndrome, as well as being a result of traumatic brain injury or cranial irradiation. Accordingly, GSK-3 has been identified as an important therapeutic target for cognitive impairment, and recent preclinical studies have yielded important evidence demonstrating that GSK-3 inhibitors may be useful therapeutic interventions for restoring cognitive function in some of these brain disorders. The current review summarises the role of GSK-3 as a regulator of cognitive-dependent functions, examines current preclinical and clinical evidence of the potential of GSK-3 inhibitors as therapeutic agents for cognitive impairments in neuropsychiatric disorders, and offers some insight into the current obstacles that are impeding the clinical use of selective GSK-3 inhibitors in the treatment of cognitive impairment.
    CNS Drugs 11/2014; · 4.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) Aβ1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the.
    Korean Journal of Physiology and Pharmacology 12/2014; 18(6):447-56. · 1.26 Impact Factor


Available from
Jun 3, 2014