News From The 19th Congress Of The European College Of Neuropsychopharmacology, Paris, September 16-20, 2006

October 1, 2006

ChEIs Beneficially Affect REM Sleep in AD. Cholinesterase inhibitors (ChEIs) do not modify disturbances of sleep-wake rhythm or sleep continuity in patients with either Alzheimer disease (AD) or frontotemporal dementia (FTD), but they may have a beneficial effect on REM sleep, according to investigators from the University of Marburg in Germany.

ChEIs Beneficially Affect REM Sleep in AD. Cholinesterase inhibitors (ChEIs) do not modify disturbances of sleep-wake rhythm or sleep continuity in patients with either Alzheimer disease (AD) or frontotemporal dementia (FTD), but they may have a beneficial effect on REM sleep, according to investigators from the University of Marburg in Germany. The team, led by Ulrich-Michael Hemmeter, MD, PhD, assistant professor in the Clinic of Psychiatry and Psychotherapy, studied sleep EEG patterns in 7 patients with AD and 6 patients with FTD. They compared polysomnographic findings taken before initiation of ChEI therapy and 5 to 10 months after ChEI therapy had begun.

The researchers noted that at baseline, all patients exhibited severe sleep continuity disturbances. REM-sleep reduction was more pronounced in patients with AD than in patients with FTD; however, unstable and disrupted REM sleep was particularly prominent in patients with FTD.

Although ChEI therapy did not affect sleep continuity variables, it did have a positive effect on REM sleep. REM sleep increased in patients with AD from 23.3 ± 22.2 minutes to 42.2 ± 23.3 minutes and REM latency was reduced from 159.5 ± 91.2 minutes to 81.8 ± 77.1 minutes. These phenomena were not seen in patients with FTD; however, REM sleep became more stabilized in these patients.The investigators surmised that impairments in cholinergic neurotransmission in patients with AD are either more severe or significantly differ from those in patients with FTD. When asked about the clinical value of the study, Hemmeter told Applied Neurology that he and his team observed a big variance in REM sleep increases in patients treated with ChEIs, ranging from nearly no increase to very strong increases. "Our findings suggest that stimulation of the cholinergic system with ChEIs may be more easily achieved in some patients than in others and that the effect of a ChEI on REM sleep may have predictive value regarding long-term therapeutic outcome," he said. Studies have shown that the quality of REM sleep affects cognition, Hemmeter added. "Therefore, increasing REM sleep with ChEI therapy may correlate with cognitive improvement or stabilization."

Childhood Adversity Linked to Reduced Dopamine Sensitivity. Childhood adversity, particularly physical abuse, may set off neurobiologic changes that include a reduction in D2 receptors. This phenomenon, in turn, may predispose a person to alcohol dependency, according to researchers from Radboud University in Nijmegen, Netherlands.

The researchers pointed to studies suggesting that dopamine receptor function is altered in alcohol-dependent persons and asked whether the dysfunction was a consequence of persistent alcohol abuse or whether the dysfunction preceded and made a person vulnerable to alcohol dependency. Using apomorphine challenge in relation to growth hormone to measure central dopamine sensitivity, the team led by A. F. A. Schellekens, MD, a specialist in substance abuse medicine at the University Medical Center St Radboud, evaluated 50 men, 38 of whom met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol dependency and 12 of whom were healthy controls. Study participants also completed 2 self-report questionnaires: the Questionnaire for Adverse Events and the Life History and Life Event Questionnaire.

The researchers found that childhood adversity scores (evaluated using the Mann-Whitney U test) were higher in alcohol-dependent patients than in controls. A significant negative correlation also was found between childhood adverse event profiles and growth hormone levels after apomorphine challenge in both patients and controls. This was particularly evident in the subcategory of physical abuse.

The research team concluded that childhood adversity might cause neurobiologic changes to the central dopaminergic system that translate into a reduction in D2 dopamine receptors and that this phenomenon, in part, may render a person more susceptible to alcohol dependency. They added that the mechanisms underlying the association between childhood adversity and D2 dopamine receptors need further scrutiny, as does the correlation between these phenomena and alcohol dependency.

The respective citations for the European College of Neuropsychopharmacology meeting presentations that correspond with these news briefs are:

  • Hemmeter UM, Rocamora R, Thum A, et al. Effects of long term treatment with cholinesterase inhibitors in patients with dementia of Alzheimer and frontotemporal type. Euro Neuropsychopharmacol. 2006;16(suppl 4):S480.
  • Schellekens AFA, Ellebroek A, De Jong CAJ, et al. Childhood adversity associated with reduced central dopamine sensitivity later in life, a premorbid vulnerability to develop alcohol dependence? Euro Neuropsychopharmacol. 2006;16(suppl 4):S494.