Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Møller, Mette; Jakobsen, Steen; Gjedde, Albert

doi:10.1038/sj.npp.1301310

Cited by 46 publications

(28 citation statements)

References 47 publications

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“…Integrity of white matter, which is typically assessed with diffusion tensor imaging (DTI) 123 , also is reduced in old compared to young adults [124][125][126] . In addition to structural changes, age reductions in neurotransmitter binding potential and receptor density have been found for both dopamine [127][128][129] and serotonin 130,131 . Finally, the incidence of dementing illnesses such as AD increases with age 132 , making the impact of risk factors for AD in healthy older adults an area of interest.…”

Section: Factors Influencing Age Differences In Cognition and Brain Amentioning

confidence: 99%

The cognitive neuroscience of ageing

2012

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PrefaceThe availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive aging. Although there is a growing consensus that the aging brain retains considerable plasticity of function, currently measured primarily by means of functional magnetic resonance imaging, it is less clear how age differences in brain activity relate to cognitive performance. The field also is hampered by the complexity of the aging process itself and the large number of factors that are influenced by age. In this review, current trends and unresolved issues in the cognitive neuroscience of aging are discussed.

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Section: Factors Influencing Age Differences In Cognition and Brain Amentioning

confidence: 99%

The cognitive neuroscience of ageing

2012

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“…A decline with age is described for the 5-HT 1A receptors in both genders (Moller et al, 2007;Tauscher et al, 2001), in women only (Costes et al, 2005) and men only (Cidis Meltzer et al, 2001;Rabiner et al, 2002). Studies involving the serotonin transporter have described localized decreases with age in varying regions (Kalbitzer et al, 2009;Meyer et al, 2001;Reimold et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Madsen

Haahr

Marner

et al. 2011

J Cereb Blood Flow Metab

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Experimental studies indicate that the 5-HT 4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT 4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [ 11 C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BP ND , was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT 4 receptor binding in the limbic system. The lower limbic 5-HT 4 receptor binding in women supports a role for 5-HT 4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT 4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.

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“…Although the receptor binding potentials (BP ND ) globally decline in depression, other diseases reveal only subtle changes, and demographic, physiologic, and psychologic measures do not consistently explain the highly variable receptor availability reported for healthy subjects. We recently reported a 3% reduction of the availability of the BP ND of this receptor per decade of life in healthy volunteers (9), but the evidence for an age-related decline is still subject to uncertainty because of the wide variability of the results (7,10,11).…”

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confidence: 99%

“…In a previous study, we compared the results of the MLSRTM with other methods used in current research (9), and in this study we compared Hypotime with the MLSRTM. With Hypotime, the highest values were found in the hippocampus and insula, whereas with the MLSRTM, no significant differences were observed among the regional values.…”

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confidence: 99%

Parametric Mapping of 5HT_1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values

Møller¹,

Rodell²,

Gjedde³

2009

J Nucl Med

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The radioligand [carbonyl-11 C]WAY-100635 ( 11 C-WAY) is a PET tracer of the serotonin 5HT 1A receptors in the human brain. It is metabolized so rapidly in the circulation that it behaves more as a chemical microsphere than as a tracer subject to continuous exchange between the circulation and brain tissue. Although reference tissue methods are useful as analyses of uptake of some radioligands with indeterminate arterial input functions, their use to analyze 11 C-WAY uptake and binding is challenged by the rapid plasma metabolism, which violates the assumption that regions of interest and reference regions continue to exchange radioligand with the circulation during the entire uptake period. Here, we proposed a method of calculation (Hypotime) that specifically uses the washout rather than the accumulation of 11 C-WAY to determine binding potentials (BP ND ), without the use of regression analysis. Methods: A total of 19 healthy volunteers (age range, 23-73 y) underwent PET to test the Hypotime application of the chemical microsphere properties of 11 C-WAY to identify regions of binding and nonbinding on the exclusive basis of the rate of washout of 11 C-WAY. Results: The results of the Hypotime method were compared with the simplified but multilinearized reference tissue method (MLSRTM). The distribution of receptor BP ND obtained with Hypotime was consistent with previous autoradiography of postmortem brain tissue, with the highest values of BP ND recorded in the medial temporal lobe and decline of receptor availability with age. The values in the basal ganglia and cerebellum were negligible. The MLSRTM, in contrast, yielded lower BP ND in all regions and only weakly revealed the decline with age. Conclusion: The simple and computationally efficient Hypotime method gave reliable values of BP ND without the use of regression. The MLSRTM, on the other hand, appeared to be affected by the early disappearance of the radioligand from the circulation and the associated uncertain late presence of 11 C-WAY in the circulation.

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Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Cited by 46 publications

References 47 publications

The cognitive neuroscience of ageing

The cognitive neuroscience of ageing

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Parametric Mapping of 5HT_1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values

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Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Cited by 46 publications

References 47 publications

The cognitive neuroscience of ageing

The cognitive neuroscience of ageing

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

Parametric Mapping of 5HT1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values

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Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Parametric Mapping of 5HT_1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values