Age-Related Cognitive Deficits Mediated by Changes in the Striatal Dopamine System

Bäckman, Lars; Ginovart, Nathalie; Dixon, Roger A.; Wahlin, Tarja-Brita Robins; Wåhlin, Åke; Halldin, Christer; Farde, Lars

doi:10.1176/ajp.157.4.635

Cited by 314 publications

(161 citation statements)

References 14 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…41). In humans, aging-related attenuation of the striatal D2-receptor binding mechanism is statistically associated both with decreased glucose metabolism in extrastriatal cortical regions innervated by dopaminergic pathways 18 and with age differences in processing speed and episodic memory 42 .…”

Section: Neurobiological Levelmentioning

confidence: 99%

Aging cognition: from neuromodulation to representation

Lindenberger

Sikström

2001

Trends in Cognitive Sciences

797

687

View full text Add to dashboard Cite

Section: Neurobiological Levelmentioning

confidence: 99%

Aging cognition: from neuromodulation to representation

Lindenberger

Sikström

2001

Trends in Cognitive Sciences

797

687

View full text Add to dashboard Cite

“…In humans, molecular imaging studies have related higher D2 receptor binding in hippocampus to better recall of verbal (Takahashi et al, 2007) and pictorial (Takahashi et al, 2008) memory. Relatedly, striatal D2 receptor density has been associated with better performance across different episodic memory tasks (Bäckman et al, 2000;Cervenka et al, 2008).…”

Section: Dopaminergic Modulation Of Episodic Memorymentioning

confidence: 99%

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Papenberg¹,

Li²,

Nagel³

et al. 2014

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

a b s t r a c tBoth the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20e31 years; n ¼ 670) and older (59e71 years; n ¼ 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

show abstract

“…There is a 2% to 6% loss of dopaminergic neurons in the SN/VTA per decade (Fearnley and Lees, 1991), and this loss is correlated with the decrease in striatal dopamine availability (Snow et al, 1993). In older adults, behavioral deficits in episodic memory are better accounted for by D2 receptor binding than by age (Backman et al, 2000). Recently, Bunzeck et al (2007) quantified age-related structural degeneration of the mesolimbic system in healthy elderly using magnetization transfer ratio (MTR) and correlated it with mesolimbic hemodynamic responses (HRs) to stimulus novelty.…”

Section: Introductionmentioning

confidence: 99%

Basal forebrain integrity and cognitive memory profile in healthy aging

Düzel¹,

Münte²,

Lindenberger³

et al. 2010

Brain Research

View full text Add to dashboard Cite

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. IntroductionAge-related decline in learning and memory, often termed age-associated memory impairment (AAMI) (Crook et al., 1986), is a well-documented finding in healthy older adults (Balota et al., 2000;Cabeza et al., 2000;Craik, 1994;Salthouse, 2003), but the neurobiological correlates of this decline are still under debate. A consistent pattern of AAMI is a decrement in declarative memory (Tulving, 1985) most clearly apparent in impaired free recall and recollection (Buckner, 2004;Craik, 2006;Hedden and Gabrieli, 2004;Nilsson, 2003). Evidence from lesion studies in humans and animals indicates that

show abstract

Age-Related Cognitive Deficits Mediated by Changes in the Striatal Dopamine System

Abstract: D(2) receptor binding is a more important factor than chronological age in accounting for variation in cognitive performance across the adult lifespan. Changes in dopaminergic neurotransmission play an important role in aging-related cognitive decline.

Cited by 314 publications

References 14 publications

Aging cognition: from neuromodulation to representation

Aging cognition: from neuromodulation to representation

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Basal forebrain integrity and cognitive memory profile in healthy aging

Contact Info

Product

Resources

About