BOSTON—An older age at retirement may be associated with a significantly decreased risk of dementia, according to research presented at the 2013 Alzheimer’s Association International Conference. In a study of 429,803 retired French workers, Carole Dufouil, PhD, and colleagues found that the hazard ratio of dementia was 0.968 for each extra year of age at retirement.
“Our results highlight the importance of maintaining high levels of cognitive and social stimulation throughout work and retiree life and emphasize the need for interventions and policies to help older individuals achieve such cognitive and social engagement,” stated Dr. Dufouil, Director of Research in Neuroepidemiology at INSERM in Paris.
The investigators based their findings on an analysis of health and pension databases that included self-employed workers (average age, 74) who were living and retired as of December 31, 2010. All workers had been retired for an average of more than 12 years. Dementia cases were defined according to a diagnosis per the ICD-10 or whether the participant had filed a claim for donepezil, galantamine, or rivastigmine. Hazard ratios were computed after the researchers adjusted for gender, marital status, occupational category, type of retirement, pension amount, diagnosis of hypertension, and diabetes. The researchers also conducted sensitivity analyses to assess potential reverse causation and differential cohort or temporal diagnosis biases.
The overall prevalence of dementia in the cohort was 2.65%. Dr. Dufouil noted that a person who retired at 65 had about a 15% lower risk of dementia, compared with a person who retired at 60.
The researchers’ results were unchanged and highly significant after they excluded workers who had had a diagnosis of dementia within five years following retirement. The findings were similar in further analyses that were stratified by age categories or year of dementia diagnosis.
“Our data show strong evidence of a significant decrease in the risk of developing dementia associated with older age at retirement, in line with the ‘use it or lose it’ hypothesis,” said Dr. Dufouil. “This health perspective should be taken into consideration when the age of cessation of professional activity is discussed.”
Microglial Modulator May Improve Cognitive Function in Patients With MCI
A novel microglial modulator was well tolerated and associated with sustained cognitive benefit in executive function and verbal memory for at least 64 weeks in patients with mild cognitive impairment (MCI), researchers reported.
“This is one of the first studies indicating that this neuroinflammatory inhibitor [CHF5074] may be able to improve cognition in people with MCI who carry the APOE4 gene,” said Joel S. Ross, MD, Founder and Chief Executive Officer of the Memory Enhancement Center of America, in Eatontown, New Jersey. “CHF5074 was well tolerated by people with MCI at doses up to and including 400 mg/day.”
Dr. Ross and colleagues reported results of a 76-week open-label extension study involving CHF5074 (Chiesi Pharmaceuticals; Parma, Italy). The extension study followed a 14-week, double-blind, placebo-controlled study of 96 patients with MCI that assessed three titrated dose regimens (200, 400, and 600 mg/day). A total of 74 patients enrolled in the extension study and received CHF5074 at the dose equal to that of their originally assigned double-blind study cohort. All participants were monitored for vital signs, cardiac activity, neuropsychologic performance, and safety laboratory parameters.
In the open-label study, 26 patients received 200 mg/day of CHF5074, 21 patients received 400 mg/day, and 27 received 600 mg/day. At week 40, 14 patients dropped out—four in the 200-mg/day group, two in the 400-mg/day group, and eight in the 600-mg/day group. Three dropouts were due to adverse events. Gastrointestinal disorders were the most frequent treatment-emergent adverse events; diarrhea was reported by 1.4% of patients taking 200 mg/day of CHF5074, by 6.3% of patients taking 400 mg/day, and by 16.0% of patients taking 600 mg/day.
“An interim analysis of cognitive tests of 27 patients reaching study week 88 showed statistically significant, dose-dependent improvements in participants’ cognitive abilities,” said Dr. Ross. “APOE4 carriers performed significantly better than APOE4 noncarriers on Immediate Word Recall and Trail Making Test–A, with improvements representing 25% to 38% of baseline scores.
“Inhibiting microglia has significant treatment potential,” Dr. Ross concluded.
BACE Inhibitor Lowers Beta-Amyloid Levels in Patients With Mild to Moderate Alzheimer’s Disease
A beta-secretase (BACE1) inhibitor significantly lowered CSF beta-amyloid levels in patients with mild to moderate Alzheimer’s disease in a dose-dependent fashion, according to Mark S. Forman, MD, PhD.
“This is the first demonstration of the lowering of beta-amyloid levels by a BACE1 inhibitor [MK-8931] in people with Alzheimer’s disease,” said Dr. Forman, Director of Clinical Research at Merck Research Laboratories in Boston, and colleagues. “We believe this candidate presents a unique opportunity to test the amyloid hypothesis.”