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...related cognitive decline (Ronnlund et al., 2005). Although the reasons for the discrepant findings remain unclear, it should be noted that most relevant studies involve relatively few subjects, and several studies may not have covered a sufficiently wide age range. Conceivably, these factors underlie the different function forms relating age to DA markers in the extant literature. The age-related loss of DA markers may have multiple loci at a neuronal or molecular level. First, there is an agerelated reduction of DA cell bodies in substantia nigra, with an average loss around 3% per decade (Fearnley and Lees, 1991). In a unique study, post-mortem cell counts in the substantia nigra were highly related to an ante-mortem imaging marker for DA synthesis capacity (Snow et al., 1993). This suggests that neuronal number influences the total synthesis rate of DA. Second, there is a reduction of synapses that progresses from childhood through adulthood to old age, which may reflect both adaptive, plastic processes during development and predominantly non-adaptive loss in late life (Gopnic et al., 1999). Third, there is evidence suggesting an age-related decrease in the number of biomarker proteins per cell. Spe...

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...) in humans is a slowly progressive neurodegenerative disease that becomes clinically manifest only after an estimated 70% of vulnerable dopaminergic neurons in the substantia nigra have already died =-=(1)-=-. Thus, modeling changes in pre-symptomatic patients is crucial for understanding pathogenesis and, perhaps even more importantly, for identifying therapeutic targets that might help to slow the disea...

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...(Qa(t)(t)) parameter estimates in older adults who performed better on L-DOPA were significantly more negative on L-DOPA compared to placebo (‘win more on L-DOPA’ group, Qa(t)(t)) placebo vs. L-DOPA t=-=(14)-=- = 2.26, p = . 040; Figure 3b). In contrast, L-DOPA did not affect expected value representation in the ‘win less on L-DOPA’ group (t(16) = 1.18, p = .257), or reward representation in either the Chow...

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.... Cell loss in PD mainly occurs in the ventral tier of the SNc. At post mortem, only a quarter of cells in the SNc remain in PD compared with normal, with the surviving cells being in the dorsal tier =-=[21]-=-. In normal ageing, the dorsal tier is preferentially affected by a ratio of over 3:1 [11] with a 5% loss per decade after the age of 40 years. The pattern of cell loss seen in PD does not occur in ot...

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...gic neurons [32]. Moreover, despite the fact that TH is the rate limiting enzyme in catecholamine synthesis there is no clear correlation between the degree of NM pigmentation and TH immunoreactivity =-=[33,34]-=-. We therefore asked, whether ΔmtDNA levels are generally higher in catecholaminergic than in non-catecholaminergic neurons. We found that in noradrenergic neurons of the LC, ΔmtDNA were not elevated ...

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...f the186 FILOTEO, MADDOX, SALMON, AND SONG SNpc are primarily affected early in the course of PD, but as the disease progresses more medial portions of the SNpc become involved (Damier et al., 1999; =-=Fearnley & Lees, 1991-=-; Gibb, 1991; Rinne et al., 1989). This pattern of neuropathological progression is consistent with the clinical observation that motor functions are affected first in PD and that cognitive functions ...