Lifestyle Factors, Medical Problems May Impact Early-stage Cognition

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by Steve Bryson, PhD |

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Lifestyle factors and co-existing medical conditions influence cognition in people in the early stages of Parkinson’s disease, with physical exercise and cognitive stimulation shown to have a protective effect, a large study revealed.

High blood pressure, diabetes, and psychiatric problems were found to have a negative impact on cognitive status, with diabetes shown to triple a patient’s risk of mild cognitive impairment.

Meanwhile, metabolic variables — such as a patient’s levels of iron, vitamin B12, the amino acid homocysteine, and pro-inflammatory immune regulatory proteins in the blood — also affected early-stage cognition, according to researchers.

These findings “reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with [Parkinson’s disease],” the scientists wrote.

Making lifestyle changes and better treating other medical problems may help improve disease management — and protect cognition — in patients with early Parkinson’s, the study suggests.

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The study, “Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson’s disease,” was published in the journal BMC Neurology.

Growing evidence suggests that changes in cognition can be observed from the onset of Parkinson’s, and that a significant proportion of patients go on to develop disease-related dementia.

At diagnosis, mild cognitive impairment is seen in up to 36% of patients, increasing to impact up to 57% after 3.5 years. Such impairment progresses to dementia within four years in about 36% of cases.

Understanding and recognizing the mechanisms that lead to problems in cognition is an unmet need among patients with Parkinson’s disease. Of even more importance is identifying factors that may contribute to the progression of cognitive decline — and that can be modified. Targeting potential risk factors such as co-existing medical conditions and lifestyle changes may aid in disease management and benefit clinical trials with cognitive outcomes.

To address these concerns, researchers based at the Hospital de la Santa Creu i Sant Pau, in Spain, and their colleagues, designed a study to identify modifiable risk factors for cognitive impairment in early-stage Parkinson’s.

“Based on a large and representative sample of patients with early-stage [Parkinson’s disease], our main objectives were to explore the possible contribution of potentially modifiable comorbid variables and lifestyle factors to global cognitive functioning,” the team wrote.

The team collected data from the COPPADIS study — a five-year observational investigation that includes patients at multiple centers across Spain and aims to further shed light on the course of the disease.

The information included disease-related clinical assessments, medicinal use, lifestyle factors, comorbidities, or co-existing medical conditions, and blood tests. The Parkinson’s Disease-Cognitive Rating Scale (CRS) was applied to evaluate cognitive status.

The study involved 533 patients with a mean age of 62.5 and a mean disease duration of 5.52 months. Among them, 114 (21%) showed mild cognitive impairment, and 26 (4.8%) were diagnosed with dementia. Overall, no significant differences in disease duration, body weight, or medication use were observed between groups with different cognitive abilities.

Although there was no difference in age between participants with either mild cognitive impairment or dementia, these individuals were significantly older than those with intact cognitive abilities. In addition, the proportion of patients who attended secondary school or university was significantly higher in the group without cognitive problems.

Disease duration was not associated with overall cognitive status, “supporting the idea that disease duration is not necessarily associated with the extent of cognitive deterioration, at least during the early stages of [Parkinson’s disease], and that other factors intervene in this population,” the researchers wrote.

In participants with mild cognitive impairment, the overall total CRS scores were significantly worse than among those without impairment — though significantly better than patients with dementia. The results were the same for all subtest CRS scores, which included factors such as immediate verbal memory, sustained attention, and working memory.

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The prevalence of psychiatric symptoms with clinically relevant severity differed significantly between groups for apathy and dysphoria — a general state of unhappiness, dissatisfaction, or frustration. These differences were driven by dysphoria in the mild impairment group (41.8%) and the dementia group (33.3%).

A progressively higher prevalence of apathy was found in all three groups: 21.4% in patients without cognitive impairment, 35.4% in those with mild cognitive impairment, and 42.9% in the dementia group. The presence of clinically relevant apathy doubled the odds of mild cognitive impairment and increased the odds for dementia 2.2 times.

While there were no differences between groups in the proportion of patients engaged in regular exercise or performing ongoing cognitive stimulation, higher total CRS scores — indicating better cognition — were significantly associated with regular physical exercise and cognitive stimulation. Specific data that could potentially guide researchers was lacking, however, the team noted.

“Unfortunately, the data analyzed do not allow us to specify which type of physical and cognitive exercise, or the frequency of such activities, could be potentially beneficial,” the researchers wrote.

Regarding other medical conditions, the prevalence of high blood pressure — also called hypertension — was significantly higher in patients with mild cognitive impairment (45.6%) than those with no impairment (30.3%) or dementia (34.6%). Hypertension almost doubled the risk of mild impairment, the investigators noted.

Diabetes also was more prevalent in the mild impairment group (15.8%) and the dementia groups (15.4%) than the cognitively normal group (5.6%). Here, diabetes tripled the risk of mild cognitive impairment and doubled the risk of dementia.

Higher levels of one or more kinds of lipids (fats), such as cholesterol, were significantly higher in both the mild impairment patients (39.5%) and dementia patients (38.5%) compared with those without impairment (28.8%). Smoking history, alcohol intake, and the use of vitamin supplements did not appear to impact cognitive status in the early stages of Parkinson’s, according to researchers.

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Statistical analysis revealed significant associations between higher CRS total scores (better cognition) and younger age, higher education level, and less severe disease. Significant associations between total CRS scores and apathy scores were found, independent of age, education, and motor status.

Lower CRS total scores (worse cognition) correlated with higher levels of the pro-inflammatory immune regulating proteins interleukin-2 and interleukin-6, as well as homocysteine — an amino acid, which are the building blocks of proteins — and iron.

As these values also were strongly linked with age and daily L-dopa dose — the primary Parkinson’s medication — a further adjusted analysis was conducted. A significant association between total CRS score and vitamin B12 values, homocysteine, and iron levels remained after these adjustments, the scientists reported.

“Both increased homocysteine and decreased vitamin B12 levels have been associated with mild cognitive impairment and risk of progression to Alzheimer’s type dementia, vascular dementia, and cognitive impairment in [Parkinson’s disease],” they wrote.

A final model was calculated that included factors such as age, education, disease severity, comorbidities, non-motor and psychiatric symptoms, cognitive performance, lifestyle factors (exercise, smoking, and alcohol intake), and blood-sample measurements.

Age, education level, and dysphoria were the strongest predictors of mild cognitive impairment, this analysis found, while age, education, disease severity, and apathy severity best predicted dementia. No associations were found between mild impairment and blood tests, whereas high interleukin-6 was associated with dementia.

“Metabolic variables such as interleukins, homocysteine, iron, and vitamin B12 have an impact on cognitive status in early [Parkinson’s disease] patients, and physical exercise and cognitive stimulation have a protective effect,” the team concluded.

“Beyond the main [disease-related] mechanisms that influence the progression of cognitive impairment in [Parkinson’s disease], our data also support the need to consider other frequent comorbidities and variables related to lifestyle when addressing cognitive impairment,” they added.