Franklin Santana Santos

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

BACKGROUND Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimers disease, although no benefits were obtained from short-term treatment. AIMS To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). METHOD 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. RESULTS 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 Alzheimers Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. CONCLUSIONS The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimers disease.

Incidence, Clinical Features and Subtypes of Delirium in Elderly Patients Treated for Hip Fractures

Objective: To describe the incidence, risk factors and clinical features (subtypes) of delirium during the postoperative period after hip fracture surgery in elderly patients. Design: Prospective study. Methods: Thirty-four consecutive patients (9 men and 25 women) were included in this study between June 16 to July 14, 2003. All patients underwent surgery for a fractured neck of femur and were pre- and postoperatively cared for at a combined geriatric/orthopedic ward. Assessment: The diagnosis of delirium was based on the criteria of the DSM-IV and the Confusion Assessment Method Scale. Subtypes of delirium were classified according to the criteria proposed by Lipowski: hyperactive-hyperalert (or agitated), hypoactive-hypoalert (somnolent) and mixed delirium. Results: Fifty-five percent (n = 19) of the 34 patients developed delirium after surgery. The development of delirium was associated with the medication midazolam taken perioperatively. Nine (47%) of the delirious patients had a hyperactive type of delirium; 5 (26%) developed a hypoactive delirium, and 5 (26%) had a mixed type. We did not find any association among subtypes of delirium and clinical features. Conclusions: Delirium is a common complication in the postoperative period of elderly patients treated for hip fractures. The use of midazolam in the perioperative period increased the risk of developing postoperative delirium. Thehyperactive type of delirium was the most common subtype of delirium.

Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized, placebo-controlled trial followed by single-blind extension.

BACKGROUND Recent studies evaluated the disease-modifying properties of lithium in mild cognitive impairment and dementia. Although potentially effective for these purposes, chronic lithium use in regard to safety in the elderly needs to be better explored. OBJECTIVE To evaluate the effect of long-term lithium treatment at subtherapeutic doses on renal function in older adults. Secondary aims were to evaluate the clinical safety and tolerability of this treatment and its effects on thyroid, immune, and glycemic functions. METHOD Between February 2007 and October 2011, a 2-year randomized, double-blind, placebo-controlled trial followed by a single-blinded phase for an additional 2 years. Sixty-one patients with mild cognitive impairment (Mayo Clinic criteria) were randomized to receive lithium or placebo. Renal function was estimated by the abbreviated Modification of Diet in Renal Disease (aMDRD) and the Chronic Kidney Disease-Epidemiology study (CKD-EPI) equations. Leukocytes, serum thyroid-stimulating hormone (TSH) and free thyroxine (T₄), and serum glucose and insulin were determined. Tolerability was evaluated at 3-month intervals through systematic clinical examinations and by the UKU Side Effect Rating Scale. RESULTS Analysis of longitudinal regression indicated that no significant changes in renal function were detected by the aMDRD (P = .453) and CKD-EPI (P = .213) equations after 4 years of lithium treatment. Significant increases in the number of neutrophils (P = .038), serum TSH (P = .034), and body weight (P = .015) were observed in the lithium group. The lithium group presented more overall adverse events (P = .045), particularly interfering in daily activities (P < .001). In addition, those patients had a higher incidence of diabetes mellitus (P = .037) and arrhythmia (P = .028). CONCLUSIONS Chronic use of lithium at low doses did not affect renal function and was clinically safe. However, some other potentially relevant adverse events were observed and others could not be ruled out due to limitations of the study design. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01055392.

Quality of life and Alzheimer's disease: Influence of participation at a rehabilitation center

Quality of life is seldom explored in evaluations of therapeutic interventions in Alzheimer’s disease. Objective To verify whether participation in a cognitive and functional rehabilitation program improves quality of life (QOL) among Alzheimer’s disease (AD) patients. Methods 19 AD patients participated in this study, 12 of whom attended 24 multi-professional intervention sessions – the experimental group – whereas the remaining 7 comprised the control group. The following tools were used to assess changes: a) Mini-Mental State Examination (MMSE); b) Geriatric Depression Scale (GDS); c) Quality of Life in AD evaluation scale (QOL-AD); d) Open question on QOL. Results Participation had no positive impact on quantitative clinical variables (MMSE, GDS, QOL-AD). The answers to the open question, examined using the Collective Subject Discourse (CSD) method, suggested that QOL improved after the intervention. Conclusion Combining pharmacological treatment with psychosocial intervention may prove to be an effective strategy to enhance the QOL of AD patients.

Death, End of Life Experiences, and Their Theoretical and Clinical Implications for the Mind–Brain Relationship

The attitude towards death and dying depends on the culture. In prehistoric times grave artifacts suggest a belief in the continuation of life. This belief in an afterlife has continued through different cultures and societies to the present day. The fear of death seems to have grown in parallel with those religions which have promised judgment at the time of death. In our modern Western secular society death is regarded as a medical failure, the rituals which used to attend it have largely been abandoned, and life is prolonged so that death has lost all dignity. It is now beginning to be recognised that dying may not be a simple switching off, but a process leading to death and the gradual dissolution of consciousness. This dissolution seems to involve experiences for the dying which are spiritual and important for them. A number of these phenomena raise the possibility that consciousness may not be limited to the brain, but extend beyond it. Fortunately, palliative care is now taught in medical schools, and treatment of the dying is now recognised to be as important as treatment for the living. This article looks at the history of death, the significance of the dying process for consciousness research, and the education needed for carers of the dying.