Noninvasive assessment of aromaticL-amino acid decarboxylase activity in aging rhesus monkey brain in vivo

DeJesus, Onofre T.; Endres, Christopher J.; Shelton, Steven E.; Nickles, Robert J.; Holden, James E.

doi:10.1002/1098-2396(20010101)39:1<58::aid-syn8>3.0.co;2-b

Cited by 49 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, there is evidence that synthesis may be higher in older adults relative to young. FMT studies in humans and nonhuman primates show age-related increases in synthesis capacity (DeJesus et al, 2001; in line with findings from postmortem tissue (Kish et al, 1995). However, little is known about the impact of upregulated synthesis on cognitive performance and underlying neural activity, although it has been linked to working memory disruption (Klostermann et al, 2012; but see Landau et al, 2009).…”

Section: Introductionsupporting

confidence: 68%

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

et al. 2016

View full text Add to dashboard Cite

Aging is accompanied by profound changes in the brain's dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[18 F]fluoro-L-mtyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI to define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Together, these findings define striatal dopamine's association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.

show abstract

Section: Introductionsupporting

confidence: 68%

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Results of studies using FDOPA to measure age-related changes in dopamine synthesis have been inconsistent; some have found decreases in striatal FDOPA signal with age (Martin et al, 1989; Bhatt et al, 1991; Cordes et al, 1994) and some have found no age effect (Sawle et al, 1990; Eidelberg et al, 1993; Ishikawa et al, 1996b). One PET study of non-human primates found that FDOPA signal decreased with age while FMT signal increased with age in the same animals (DeJesus et al, 2001). The authors suggested that the disparate results related to differences in what the two tracers measure.…”

Section: Introductionmentioning

confidence: 99%

“…Because of this, most FMT signal results from tracer that has been metabolized by AADC and monoamine oxidase-A (MAO-A), and trapped in axon terminals as 6-[ 18 F]-fluoro- m -hydroxyphenylacetic acid without being released or further processed (Jordan et al, 1997). FMT signal therefore more fully represents the extent of AADC activity (DeJesus et al, 2001). Several past studies have demonstrated age-related changes in enzymes that affect post-release dopamine processing (Fowler et al, 1980; Saura et al, 1997; Rinne et al, 1998; Harada et al, 2002; van Dyck et al, 2002), potentially affecting the results of FDOPA studies.…”

Section: Introductionmentioning

confidence: 99%

Relationship of Striatal Dopamine Synthesis Capacity to Age and Cognition

Braskie¹,

Wilcox²,

Landau³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

Past research has demonstrated that performance on frontal lobe-dependent tasks is associated with dopamine system integrity and that various dopamine system deficits occur with aging. The positron emission tomography (PET) radiotracer 6-[ The varying results occur in part from tracer processing that renders FDOPA signal subject to aspects of postrelease metabolism, which may themselves change with aging. In contrast, FMT remains a purer measure of AADC function. We used partial volume-corrected FMT PET scans to measure age-related striatal dopamine synthesis capacity in 21 older (mean, 66.9) and 16 younger (mean, 22.8) healthy adults. We also investigated how striatal FMT signal related to a cognitive measure of frontal lobe function. Older adults showed significantly greater striatal FMT signal than younger adults. Within the older group, FMT signal in dorsal caudate (DCA) and dorsal putamen was greater with age, suggesting compensation for deficits elsewhere in the dopamine system. In younger adults, FMT signal in DCA was lower with age, likely related to ongoing developmental processes. Younger adults who performed worse on tests of frontal lobe function showed greater FMT signal in right DCA, independent of age effects. Our data suggest that higher striatal FMT signal represents nonoptimal dopamine processing. They further support a relationship between striatal dopamine processing and frontal lobe cognitive function.

show abstract

“…Detrimental effects of tyrosine may be less surprising when considering literature on increased dopamine synthesis capacity in older adults, which is consistently observed when using the PET tracer FMT (Dejesus et al, 2001; Braskie et al, 2008; Berry et al, 2016), although mixed results have been obtained with another aromatic amino acid decarboxylase substrate, FDOPA, with decreased signal-to-noise (Martin et al, 1989; Sawle et al, 1990; Bhatt, 1991; Dreher et al, 2008). Increased age-related dopamine synthesis was negatively correlated with reward-related BOLD signal (Dreher et al, 2008) and, similarly, the positive relation between dopamine synthesis and cognitive performance seen in young adults was absent in older adults (Berry et al, 2016).…”

Section: Discussionmentioning

confidence: 97%

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults

Bloemendaal¹,

Froböse²,

Wegman³

et al. 2018

eNeuro

View full text Add to dashboard Cite

The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning. In healthy older adults, impairments have been demonstrated in two forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing) under high information load. However, no study has directly compared the effects of a catecholamine precursor on reactive and load-dependent proactive inhibition. In this study we explored the effects of tyrosine on reactive and proactive response inhibition and signal in dopaminergically innervated fronto-striatal regions. Depending on age, tyrosine might lead to beneficial or detrimental neurocognitive effects. We aimed to address these hypotheses in 24 healthy older human adults (aged 61–72 years) using fMRI in a double blind, counterbalanced, placebo-controlled, within-subject design. Across the group, tyrosine did not alter reactive or proactive inhibition behaviorally but did increase fronto-parietal proactive inhibition-related activation. When taking age into account, tyrosine affected proactive inhibition both behaviorally and neurally. Specifically, increasing age was associated with a greater detrimental effect of tyrosine compared with placebo on proactive slowing. Moreover, with increasing age, tyrosine decreased fronto-striatal and parietal proactive signal, which correlated positively with tyrosine’s effects on proactive slowing. Concluding, tyrosine negatively affected proactive response slowing and associated fronto-striatal activation in an age-dependent manner, highlighting the importance of catecholamines, perhaps particularly dopamine, for proactive response inhibition in older adults.

show abstract

Noninvasive assessment of aromaticL-amino acid decarboxylase activity in aging rhesus monkey brain in vivo

Cited by 49 publications

References 27 publications

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

Relationship of Striatal Dopamine Synthesis Capacity to Age and Cognition

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults

Contact Info

Product

Resources

About