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Abstract
Age-related motor slowing is a significant predictor of dementia. This syndrome comprises clinical features similar to Parkinson’s disease (PD), without meeting its clinical criteria, and possibly represents pre-clinical PD. In PD, the pre-supplementary motor area (pre-SMA), which has strong connections to the prefrontal cortex and is involved in the preparatory planning and rehearsal of motor and cognitive tasks undergoes marked neuronal loss. Whether individuals with motor slowing exhibit early changes in the pre-SMA is unknown. Pre-SMA activation was investigated in motor slowed adults, compared to young and age-matched healthy controls (free of extrapyramidal features), and PD patients, during two blocked design fMRI experiments. The first experiment used a modified Sternberg paradigm, where participants were instructed to maintain either 1 or 6 letters in working memory. The alternating conditions each comprised 6 blocks of 4 trials. In the second experiment, participants were instructed to imagine a simple hand movement repeatedly. This condition was presented 9 times across 3 runs alternating with rest periods. In addition, transcranial sonography was used to detect structural substantia nigra changes, appearing as hyperechogenicity. Motor slowed adults showed reduced pre-SMA activation, compared to healthy controls, in the 6-letter versus 1-letter working memory task, of the first experiment only. Additionally, they had a significantly hyperechogenic substantia nigra, compared to healthy adults, but similar to PD patients. Meanwhile, reduced pre-SMA activation was observed in adults with substantia nigra hyperechogenicity in the imagine versus rest contrast of the second experiment only, compared to adults with normal substantia nigra echogenicity. From these original observations, it is concluded that the clinical presentation of parkinsonian motor signs is correlated with functional changes in the pre-SMA during a working memory task, and a hyperechogenic substantia nigra is associated with pre-SMA changes during motor imagination. Whilst further studies are necessary, it is postulated that both groups of older adults are in the pre-clinical stages of PD. Thus, due to the similar brain changes observed between older motor slowed adults and PD patients, it is concluded that age-related motor slowing is a strong candidate for pre-clinical PD.