Working Memory Impairment Occurs Before Cognitive Decline, Study Finds

The inability to remember proper sequences of information, such as numbers or events, occurs before cognitive impairment in Parkinson’s patients who have mild motor symptoms, a Chinese study shows.

The research “Impaired serial ordering in nondemented patients with mild Parkinson’s disease,” was published in the journal PLOS ONE.

The ability to arrange thoughts and actions in an appropriate serial order is essential to complex behaviors such as language, reasoning and cognitive planning. Parkinson’s patients perform poorly in tasks that rely on the successful rearrangement of working memory representations, such as difficulties in finding the order of letters or events, or understanding the temporal relation of events that are expressed out of chronological order.

Prior studies have not been able to determine how impaired serial ordering develops throughout Parkinson’s disease. In particular, scientists still debate if this impairment is a reflection of severe motor symptoms or of cognitive decline.

The study authors hypothesized that deficits in serial ordering occur in early stages of the disease, before subtle changes in cognition and simultaneously with motor symptoms.

Forty-nine patients with mild motor symptoms were evaluated for their ability to perform serial ordering tests. Patients either had no deficits in cognition, or mild cognitive impairment.

Specifically, patients’ ability to order numbers in verbal working memory was assessed with the adaptive digit ordering test (DOT-A). In this test, participants are presented three to eight digits in a random order and asked to recall them immediately in ascending order.

The scientists also conducted the digit span forward and backward tests, which are commonly used to evaluate short-term recall of digit sequences. Using both tests was intended to rule out whether Parkinson’s patients have difficulties only in ordering ascending sequences, or if their deficits occur in both ascending and descending approaches.

The team predicted that Parkinson’s patients without dementia would perform worse than healthy controls in the DOT-A and backward tests, but not in the digit-forward test. This would mean that patients in early stages of Parkinson’s would maintain verbal recall, but would have impaired ability to reorder sequences.

Compared to the 51 healthy controls, patients performed worse in both digit ordering and backward tests, although they performed normally in the forward test. This was observed both in patients with normal cognition and those with mild cognitive impairment.

The data also revealed an age-related decline in serial ordering, meaning that patients perform worse as they get older. However, patients’ test results did not correlate with severity or duration of motor symptoms, or with daily exposure to dopaminergic medications.

“These results suggested that serial ordering deficits exist in early stages of [Parkinson’s], prior to subtle changes in global cognition and in parallel with motor symptoms,” the researchers wrote.