Neurology: Weight changes in patients with early Parkinson's disease may be associated with long-term cognitive changes

Parkinson's disease (PD) is the second most common chronic neurodegenerative disease, with statistics on more than 10 million PD patients worldwide, nearly 30% of whom are in China
.
China ranks first in the world in the number of patients, and its prevalence in the elderly population over 65 years old is as high as about 2% [1].

With the aging of the population and the extension of life expectancy, the number of PD patients will increase by more than 50% by 2030, bringing a heavy burden to families and society [2].

The main clinical manifestations of PD are gradually worsening motor and non-motor symptoms, and these clinical manifestations can affect the body's energy balance by changing dietary intake and increasing energy expenditure, and affecting nutrient metabolism [3].

Weight loss is one of the most common non-motor symptoms in patients with PD, usually occurring years before the onset of typical motor symptoms [4], and weight gain is also common in PD but not well understood
.

While an association between weight change and dementia risk in older populations has been reported in many studies, there is a lack of strong evidence
linking early weight change to cognitive ability in people with PD.

One study showed that weight loss was associated with faster overall cognitive decline in patients with PD [5], and another study confirmed that early weight loss was associated with dementia progression in patients with PD [6], but there were limitations in the design
.
In addition, the effect of weight gain on cognitive function in patients with early PD is still unknown, and no studies have emerged
to assess the decline trajectory of specific cognitive domains (such as executive ability, language fluency, etc.
) based on early PD weight changes.

Recently, a research team led by Jin-Sun Jun of the Department of Neurology at Gangnam Sacred Heart Hospital in South Korea published important research results in the top journal Neurology [7].

Their findings suggest that early weight changes in PD patients are associated
with long-term cognitive changes.
Specifically, early weight loss was associated with a more rapid decline in overall cognitive function and executive performance, while early weight gain was associated
with slower work processing speed and slower attention loss.

Next, let's take a look at how this research unfolds
.

The study is based on a large, multicenter, international prospective cohort study of Parkinson's disease progression markers (PPMI), from which researchers screened 358 PD patients and 174 healthy control (HC) participants for an 8-year follow-up study
.

Weight is measured by dressing and weighing while fasting, and then weighing
again at the same time every year.
Using weight data at baseline and 1 year follow-up, this review identified weight change of more than 3% as early weight change (gain, loss).

First, compared with the HC group, patients with PD had more severe motor and non-motor symptoms, with significant weight loss within 1 year (PD: −1.
0±5.3%, HC: 1.2±8.0%; P=0.004）
。 According to the rate of weight change, PD patients were divided into weight loss group (98 cases), body weight change group (201 cases) and weight gain group (59 cases), and the average weight changes of the three groups in one year were −7.1±4.8%, −0.1±1.6%, and 6.1±2.9%,
respectively.

The assessment of cognitive function is divided into global cognition and different levels of cognitive domains, and the assessment of overall cognitive function uses the Montreal Cognitive Assessment (MoCA) scale
.
MoCA is a widely used tool for assessing cognitive function in PD patients and is more sensitive
than a simple mental state examination (MMSE) in identifying cognitive deficits.

The results of the linear mixed-effects model adjusted for multivariate correction showed that the MoCA score of the weight loss group decreased faster than that of the body weight unchanged group (β=−0.19, 95%CI=−0.28~−0.10, t=−3.18, P=0.001).

However, no significant difference in MoCA score change was found between the weight gain group and the no change in weight group (P = 0.850).

Correlation between MoCA scores and early weight change in patients with PAR PD

For specific cognitive domains, memory was assessed using the Hopkins Language Learning Test (HVLT), 15 Benton Line Segment Orientation Determination Test (BJLO) to assess visuospatial function, the Semantic Fluency Test (SFT) and MoCA speech fluency sections to assess language fluency, the Symbolic-Number Pattern Test (SDMT) to assess processing speed and attention, and the Alpha-Numeric Sequence Test (LNS) to assess working memory and executive function
.

The weight loss group had greater SFT (β=−0.37, 95%CI=−0.66~−0.08, t=−2.51, P=0.012) and MoCA speech fluency (β=−0.18, 95%CI=−0.31~−0.05, t=−2.79, P=0.005) scores than in the body weight unchanged group.

On the other hand, the SDMT score decline rate in the weight gain group was slower than that in the unchanged group (β=0.34, 95%CI=0.05~0.63, t=2.31, P=0.021), and there was no significant correlation between
early weight change and other cognitive domain scores.
These associations persist
in patients with baseline cognitively normal PD.

To detect sensitivity to different cut-off values, additional validation analyses
were performed using a 5% rate of change.
At this time, the effect of weight loss of more than 5% on the MoCA longitudinal score was consistent with the results when truncated by 3%, but there was no significant correlation
with the scores of each cognitive domain.
Cognitive changes with weight gain of more than 5% did not differ
from those in the group with no change in weight.

When weight change was used as a continuous variable, the effect of weight loss on cognition was also roughly similar
to when using 3% as the cut-off value.
In addition, there was a downward trend in SFT scores (β=0.03, 95%CI=−0.01~0.06, t=1.79, P=0.074) and MoCA speech fluency scores (β=0.014, 95%CI=−0.002~0.031, t=1.76, P=0.079) in patients with weight loss, but there was no statistical difference
.

However, continuous weight gain had no significant effect
on cognitive function.
Combined with the results of the primary analysis, this suggests that excessive weight gain may have adverse effects
on cognition.

Finally, the team analyzed the effects of weight changes on other non-motor symptoms, including 15 geriatric depression scales assessing depressive states, state-trait anxiety scales assessing anxiety states, rapid eye movement sleep behavior disorder (RBD) screening questionnaires assessing RBD symptoms, Epworth sleepiness scale assessing daytime sleepiness, and autonomic scale assessing autonomic dysfunction
.
The results showed that early weight change was not associated with other non-motor symptom changes, suggesting that the effect of weight change on cognition was specific
.

Overall, this study provides some evidence for early weight management in PD patients, suggesting that early weight change has different effects
on cognitive performance in PD patients.
In patients with PD, early weight loss represents faster impairment of overall cognitive and executive function, while early weight gain leads to slower
loss of processing speed and attention.

This is the first study to focus on the impact of weight change on specific cognitive domain impairment in patients with early PD, with strict inclusion/exclusion criteria, comprehensive cognitive assessments, and long follow-up
.
However, participants' weight changes were influenced by a number of factors, including clothing at the time of measurement and subjective dieting plans
.
In addition, patients with early-stage PD are less likely to experience cognitive decline, and more cohort studies are needed to verify the validity of
this result.

Future studies of targeted weight management (e.
g.
, appropriate weight gain) and dietary interventions should be conducted to explore whether they can slow cognitive decline
in patients with PD.

References

1.
Qi S, Yin P, Wang L, et al.
Prevalence of Parkinson's Disease: A Community-Based Study in China.
Mov Disord.2021; 36(12):2940-2944.
doi:10.1002/mds.28762

2.
Poewe W, Seppi K, Tanner CM, et al.
Parkinson disease.
Nat Rev Dis Primers.
2017; 3:17013.
Published 2017 Mar 23.
doi:10.1038/nrdp.2017.13

3.
Ma K, Xiong N, Shen Y, et al.
Weight Loss and Malnutrition in Patients with Parkinson's Disease: Current Knowledge and Future Prospects.
Front Aging Neurosci.
2018; 10:1.
Published 2018 Jan 19.
doi:10.3389/fnagi.2018.00001

4.
Song S, Luo Z, Li C, et al.
Changes in Body Composition Before and After Parkinson's Disease Diagnosis.
Mov Disord.
2021; 36(7):1617-1623.
doi:10.1002/mds.28536

5.
Kim HJ, Oh ES, Lee JH, et al.
Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson's disease (PD).
Arch Gerontol Geriatr.
2012; 55(1):70-72.
doi:10.1016/j.archger.2011.06.022

6.
Cumming K, Macleod AD, Myint PK, Counsell CE.
Early weight loss in parkinsonism predicts poor outcomes: Evidence from an incident cohort study.
Neurology.
2017; 89(22):2254-2261.

doi:10.1212/WNL.0000000000004691

7.
Kim R, Choi S, Byun K, et al.
Association of Early Weight Change With Cognitive Decline in Patients With Parkinson Disease [published online ahead of print, 2022 Oct 19].
Neurology.
2022; 10.
1212/WNL.
0000000000201404.
doi:10.1212/WNL.0000000000201404