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Sniffing out a link with Alzheimer's
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News & Comment
TRENDS in Cognitive Sciences Vol.6 No.7 July 2002
Journal Club
Sniffing out a link with Alzheimer’s A growing body of evidence suggests that Alzheimer’s disease is associated with a diminished sense of smell. Initially deficits are apparent in the identification and recognition of smells; later thresholds for smell detection are affected and brain areas associated with olfactory information processing and memory show decreased metabolic activity. The olfactory dysfunction might predate onset of the cognitive decline associated with Alzheimer’s disease. As early diagnosis of the condition is difficult, impaired performance on olfactory tasks with memory demands could be useful in predicting who will develop the disease. In a recent study, Schiffman et al. assessed neuropsychological and chemosensory performance in individuals at high genetic risk for developing late-onset Alzheimer’s disease [1]. Participants (mean age 60 years) were not cognitively impaired and were matched by controls for age, gender, race and education. Smell and taste functions were assessed
using a variety of stimuli at concentrations determined at pretesting to have the same intensity rating. Tests of detection threshold, memory, discrimination and identification of standardized odors and tastes were carried out. Subjects also completed a battery of neuropsychological measures. All measures were repeated approximately 18 months after the initial assessment and the experimental group was evaluated for cognitive change yearly for up to 8 years. There were apparent differences on the smell detection and memory tasks. At baseline, the ‘at-risk’ group performed worse than controls on measures of phenylethyl alcohol smell detection, smell memory and taste memory. The at-risk group also performed poorly on a recall of narrative information task, but were better than controls on a simple attentional task. At follow-up, many subjects showed improvement on the cognitive, but not on the chemosensory, measures. At both assessment times the at-risk subjects had poorer smell memory.
The decrement in smell ability was odor-specific (for example, sensitivity to menthol, an odorant with a large trigeminal component, was not related to at-risk status). Of the at-risk participants (n = 33), seven subjects (21%) changed in cognitive status 2–8 years after the baseline session; five subjects developed mild cognitive impairment and two developed Alzheimer’s disease. The data therefore suggest a modest effect of smell memory but the conclusions are constrained by the small number of affected individuals. A largerscale study might reveal whether smell detection could be a useful early diagnostic tool for Alzheimer’s. 1 Schiffman, S.S. et al. (2002) Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer’s disease. Neurobiol. Aging 23, 397–404
Fiona Lyddy [email protected]
Placebo effect really is all in your mind Simply believing that medical treatment will be beneficial to your health is, in itself, enough to bring about a significant improvement in your well-being. Despite the omnipresent nature of the placebo effect the physiological mechanisms underlying it are not well understood. Two recent PET investigations using innovative designs have provided new information about the neuroanatomical foundations of the placebo effect. Mayberg et al. measured changes in brain activity associated with successful improvement in mood after administration of either a placebo or antidepressant medication [1]. Hospitalized patients with unipolar depression were randomly allocated to a placebo or antidepressant (SSRI) condition. PET scans of the resting brain state were conducted before and after administration of placebo or medication, at week 1 and week 6 of the trial. At the end of the trial equal numbers of successful treatment ‘responders’ were identified in both conditions. Subsequent analysis of the PET data revealed that successful response to the placebo and antidepressant http://tics.trends.com
medication were both associated with a common pattern of cortical activation (frontal and posterior cingulate). Successful responders to the antidepressant medication showed additional unique areas of activation. Given that placebo responders showed marked improvement in their mood, Mayberg et al. propose that the common areas of cortical activation might be ‘necessary’ for the remission of the signs and symptoms of depression. In the other investigation, Petrovic et al. compared the brain systems involved in pain relief following the introduction of an opioid analgesia or placebo treatment [2]. While being scanned subjects were presented with painful stimuli of varying intensity and intravenously administered either opioid analgesia or a placebo (saline). In order to establish the extent to which subjects demonstrated analgesia, at the end of each scan subjects rated the intensity of the stimulus on a visual analogue scale. Comparison of the subjects’ cortical responses to pain found that opioid and placebo analgesia were associated with increased blood flow in the same areas
involved in pain management (which contained high numbers of opioid receptors). Further analysis suggested that individuals who reported relatively high levels of placebo analgesia showed greater activation of the opioid analgesia network. The findings of these studies show that a successful placebo response involves the same cortical regions as are engaged in successful pharmacological intervention. However, both studies were characterized by marked inter-subject variability with respect to the magnitude of placebo response, so future research will need to establish to what extent this variability explains individual differences in treatment responsiveness to a range of pharmacological and psychological interventions. 1 Mayberg et al. (2002) The functional neuroanatomy of the placebo effect. Am. J. Psychiatry 159, 728–737 2 Petrovic et al. (2002) Placebo and opioid analgesia: imaging a shared neuronal network. Science 295, 1737–1740
Marc Seal [email protected]
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
News & Comment
TRENDS in Cognitive Sciences Vol.6 No.7 July 2002
Journal Club
Sniffing out a link with Alzheimer’s A growing body of evidence suggests that Alzheimer’s disease is associated with a diminished sense of smell. Initially deficits are apparent in the identification and recognition of smells; later thresholds for smell detection are affected and brain areas associated with olfactory information processing and memory show decreased metabolic activity. The olfactory dysfunction might predate onset of the cognitive decline associated with Alzheimer’s disease. As early diagnosis of the condition is difficult, impaired performance on olfactory tasks with memory demands could be useful in predicting who will develop the disease. In a recent study, Schiffman et al. assessed neuropsychological and chemosensory performance in individuals at high genetic risk for developing late-onset Alzheimer’s disease [1]. Participants (mean age 60 years) were not cognitively impaired and were matched by controls for age, gender, race and education. Smell and taste functions were assessed
using a variety of stimuli at concentrations determined at pretesting to have the same intensity rating. Tests of detection threshold, memory, discrimination and identification of standardized odors and tastes were carried out. Subjects also completed a battery of neuropsychological measures. All measures were repeated approximately 18 months after the initial assessment and the experimental group was evaluated for cognitive change yearly for up to 8 years. There were apparent differences on the smell detection and memory tasks. At baseline, the ‘at-risk’ group performed worse than controls on measures of phenylethyl alcohol smell detection, smell memory and taste memory. The at-risk group also performed poorly on a recall of narrative information task, but were better than controls on a simple attentional task. At follow-up, many subjects showed improvement on the cognitive, but not on the chemosensory, measures. At both assessment times the at-risk subjects had poorer smell memory.
The decrement in smell ability was odor-specific (for example, sensitivity to menthol, an odorant with a large trigeminal component, was not related to at-risk status). Of the at-risk participants (n = 33), seven subjects (21%) changed in cognitive status 2–8 years after the baseline session; five subjects developed mild cognitive impairment and two developed Alzheimer’s disease. The data therefore suggest a modest effect of smell memory but the conclusions are constrained by the small number of affected individuals. A largerscale study might reveal whether smell detection could be a useful early diagnostic tool for Alzheimer’s. 1 Schiffman, S.S. et al. (2002) Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer’s disease. Neurobiol. Aging 23, 397–404
Fiona Lyddy [email protected]
Placebo effect really is all in your mind Simply believing that medical treatment will be beneficial to your health is, in itself, enough to bring about a significant improvement in your well-being. Despite the omnipresent nature of the placebo effect the physiological mechanisms underlying it are not well understood. Two recent PET investigations using innovative designs have provided new information about the neuroanatomical foundations of the placebo effect. Mayberg et al. measured changes in brain activity associated with successful improvement in mood after administration of either a placebo or antidepressant medication [1]. Hospitalized patients with unipolar depression were randomly allocated to a placebo or antidepressant (SSRI) condition. PET scans of the resting brain state were conducted before and after administration of placebo or medication, at week 1 and week 6 of the trial. At the end of the trial equal numbers of successful treatment ‘responders’ were identified in both conditions. Subsequent analysis of the PET data revealed that successful response to the placebo and antidepressant http://tics.trends.com
medication were both associated with a common pattern of cortical activation (frontal and posterior cingulate). Successful responders to the antidepressant medication showed additional unique areas of activation. Given that placebo responders showed marked improvement in their mood, Mayberg et al. propose that the common areas of cortical activation might be ‘necessary’ for the remission of the signs and symptoms of depression. In the other investigation, Petrovic et al. compared the brain systems involved in pain relief following the introduction of an opioid analgesia or placebo treatment [2]. While being scanned subjects were presented with painful stimuli of varying intensity and intravenously administered either opioid analgesia or a placebo (saline). In order to establish the extent to which subjects demonstrated analgesia, at the end of each scan subjects rated the intensity of the stimulus on a visual analogue scale. Comparison of the subjects’ cortical responses to pain found that opioid and placebo analgesia were associated with increased blood flow in the same areas
involved in pain management (which contained high numbers of opioid receptors). Further analysis suggested that individuals who reported relatively high levels of placebo analgesia showed greater activation of the opioid analgesia network. The findings of these studies show that a successful placebo response involves the same cortical regions as are engaged in successful pharmacological intervention. However, both studies were characterized by marked inter-subject variability with respect to the magnitude of placebo response, so future research will need to establish to what extent this variability explains individual differences in treatment responsiveness to a range of pharmacological and psychological interventions. 1 Mayberg et al. (2002) The functional neuroanatomy of the placebo effect. Am. J. Psychiatry 159, 728–737 2 Petrovic et al. (2002) Placebo and opioid analgesia: imaging a shared neuronal network. Science 295, 1737–1740
Marc Seal [email protected]
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.