parkinson 's disease ( pd ) is a chronic and progressive disorder with an estimated prevalence of 2% in adults over age 60 .
the study of disease progression and its determinants is of great importance to improve our understanding of the disease in order to optimize treatment . a wide variety of correlations between different subtypes of the disease and the progression of motor and nonmotor symptoms
have been reported . a cohort study with an eight - year follow - up found that axial symptoms ( gait and postural instability ) progress more rapidly than other motor features of pd ( tremor , bradykinesia , and rigidity ) .
likewise , a study with a nine - year follow - up reported a greater progression of motor scores in subjects with the following characteristics : male gender , older age at diagnosis , akinetic - rigid subtype , and lower baseline motor score . a slower progression of tremor in comparison to other cardinal features of pd has also been reported . on the other hand ,
nonmotor progression has been less studied . a study derived from the adagio study population demonstrated an increase of 10% in the movement disorder society unified parkinson 's disease rating scale ( mds - updrs ) part i score , which evaluates nonmotor experiences of daily living ( nm - edl ) , in the placebo group through a nine - month follow - up .
another study reported a rate of progression for nm - edl of 0.42 points per year , while progression on the motor experiences of daily living ( m - edl ) was reported to be of 0.8 points per year .
the objective of the present study is to describe the change in motor and nonmotor symptoms assessed by the mds - updrs and the nonmotor symptoms scale ( nmss ) in a real - life cohort of subjects with pd after a 21-month follow - up .
subjects with pd were recruited from the movement disorders clinic of the national institute of neurology and neurosurgery ( mexico city ) .
diagnosis was made according to the uk parkinson 's disease brain bank 's criteria by a movement disorder specialist .
the study was submitted and obtained approval from the institutional review board and local ethics committee .
full signed consent from all participants was obtained in order to participate in the study .
levodopa equivalent daily dose ( ledd ) was also calculated . the spanish version of mds - updrs , the parkinson disease quality of life questionnaire ( pdq-8 ) , and the nmss were applied to all subjects at two different cut - points ( initial evaluation and a follow - up visit at 21  3 months ) .
the full 65-item mds - updrs was applied by a neurologist with expertise in movement disorders .
the mds - updrs consists of four parts : part i , non - motor experiences of daily living ; part ii , motor experiences of daily living ; part iii , motor examination ; and part iv , motor complications .
the pdq-8 is a health status scale covering eight different dimensions of health - related quality of life .
each item is scored using a likert scale ( never , occasionally , sometimes , and always ) .
the nmss is a nine - domain scale for the evaluation of nonmotor symptoms in pd ( cardiovascular , sleep / fatigue , mood / cognition , perceptual problems / hallucinations , attention / memory , gastrointestinal tract , urinary function , sexual function , and miscellaneous ) .
each domain is assessed in terms of severity ( from 0 : none to 3 : severe ) and frequency ( from 1 : rarely to 4 : very frequent ) in the last month .
the score for each domain is obtained by multiplying frequency by severity ; total score is the sum of the nine domains .
disease severity was categorized using the recently published triangulation - based cut - offs classification of mds - updrs severity ( part i : mild 010 , moderate 1121 , and severe 22 ; part ii : mild 012 , moderate 1329 , and severe 30 ; part iii : mild 032 , moderate 3358 , and severe 59 ; part iv : mild 04 , moderate 512 , and severe 13 ) .
quantitative data such as mds - updrs , nmss , and pdq-8 scores were compared using a t - test for related samples .
ordinal data ( use of antiparkinsonian drugs ) were compared using a mcnemar test ; when more than two outcomes were present ( disease severity ) the mcnemar - bowker test was used .
fifty - three patients concluded the follow - up ( 33 women and 20 men ) . in all cases , loss to follow - up was due to migration out of the city resulting in unavailability to attend the follow - up visit . the mean age at the initial visit for the final sample was 64.1  14.3 years and the mean disease duration was 9.1  5.4 years .
comparison of treatment schemes between the initial and follow - up visits is shown in table 1 .
the frequencies for each severity group according to the mds - updrs at the initial and follow - up visits are shown in table 2 .
the comparison of total scores in the mds - updrs , pdq-8 , and nmss between visits is shown in table 3 .
no statistically significant difference was found in regard to disease severity according to the mds - updrs part iii between the initial and follow - up visits .
most of the patients remained in the mild and moderate disease groups , although there was a slight increase in the mild group as a consequence of clinical improvement in subjects initially classified as moderate severity .
the mds - updrs part iii demonstrated a statistically significant decrease of 7.2  2.3 points ( 95% ci , 3.1 to 11.2 , p = 0.001 ) between the initial and follow - up visits . when compared by disease severity , subjects with mild disease had a mean improvement of 5.7  0.1 points ( 95% ci , 3 to 8.4 , p < 0.0001 ) ; subjects with moderate disease also showed improvement although statistical significance was not reached ( 8  3.5 points , 95% ci 4.4 to 20.4 , p = 0.159 ) .
the m - edl assessed by mds - updrs part ii did not show any statistically significant change between visits . in regard to motor complications assessed by the mds - updrs part iv , a mean increase of 0.9  0.6 points ( 95% ci , 0.8 to 1.6 , p = 0.015 ) was observed .
when analyzed by severity , subjects with a mild disease worsened by 0.4  0.2 points ( 95% ci , 0.1 to 0.8 , p = 0.017 ) .
no statistically significant association was found between the mean change in the total mds - updrs score and the predominant motor phenotype ( p = 0.397 ) .
when analyzed independently , no association was found between the different mds - updrs parts and predominant phenotype ( part i p = 0.787 , part ii p = 0.286 , part iii p = 0.578 , and part iv p = 0.994 ) .
no association was found between motor scores and gender ( p = 0.427 ) or disease duration ( p = 0.941 ) .
no statistically significant change in nonmotor severity as assessed by the mds - updrs part i was found between visits with most of the patients remaining in the mild severity group .
moreover , the nm - edl score did not show a statistically significant change between the initial and follow - up visits even when accounting for severity classification .
conversely , all nonmotor symptom domains in the nmss scale showed an increase in the mean score , as shown in table 4 .
an increase of 14.3  11.4 points ( 95% ic , 0.47 to 27.4 , p = 0.043 ) in nmss total score was found between visits . even though there was an increase in the score of all domains , the difference was statistically significant only for the perceptual problems and hallucinations item ( 0.2  0.7 to 0.8  2.1 , p = 0.044 ) . when analyzing by disease severity according to the mds - updrs part i score , no statistically significant increase in nmss total score within groups
the mds - updrs part i and nmss total scores showed a high correlation ( r = 0.611 , p = 0.01 ) .
no statistically significant associations were found between nmss scores and disease duration ( p = 0.677 ) , gender ( p = 0.964 ) , or motor phenotype ( p = 0.427 ) .
no statistically significant changes were found in quality of life as assessed by the pdq-8 between visits .
pd is a progressive neurodegenerative disease . rates of change in motor and nonmotor symptoms appear to progress differently in a nonlinear fashion with a greater increase in the m - edl in comparison to the nm - edl .
traditionally , pd severity is assessed using the hoehn and yahr staging . in this regard ,
the mds - updrs severity scale was preferred instead due to the fact that the hoehn and yahr scale relies mainly on the motor state . in order to evaluate the impact of nonmotor symptoms a severity classification accounting for them was needed .
the recently published cut - off points for pd severity levels based on the mds - updrs had the advantage of including nonmotor symptoms . in the present study ,
the overall improvement of seven points in the mds - updrs part iii can be explained by several factors .
firstly , the study was carried out at a referral center and the initial evaluation was actually the first time the patient was seen at the clinic . as a consequence ,
it should be pointed out that although the ledd increased by 120  mg / d , the actual levodopa daily dose was slightly increased .
the latter means that no major levodopa dosage adjustments were performed but also that antiparkinsonian drugs were added as expected .
for instance , the use of monoamine oxidase inhibitors and the dopamine agonist ledd was doubled .
it also should be emphasized that motor evaluations were performed during the  on  clinical state , in contrast to an  off  state that could be a better index of the disease natural history . on the other hand ,
an increase in motor complications such as  on  time with troublesome dyskinesia and motor fluctuations assessed in the mds - updrs part iv was found .
motor complications related to dopaminergic treatment are expected to increase with disease progression despite better motor scores .
interestingly , no difference in m - edl ( mds - updrs part ii ) was found between visits despite the improvement in motor scales . moreover , health - related quality of life assessed by the pdq-8 also failed to show any improvement . in regard to the nm - edl ,
reported a significant worsening of nm - edl scores in the mds - updrs in the placebo group , but no change in treated patients . on the other hand , a statistically significant increase of 14% in the nmss total score was observed . even though every nmss domain had an increase in its score , only the perceptual changes and hallucinations item had a statistically significant difference .
that is , all the nonmotor symptoms worsened , but only the cumulative effect and hallucinations reached statistical significance .
a possible explanation may be that the worsening in individual nonmotor symptoms was not clinically significant and as a consequence proper management was not initiated .
for instance , use of antidepressants remained the same despite the increase in the mood domain score .
additionally , some symptoms like hallucinations can be an adverse effect of dopaminergic replacement therapy , as well as a consequence of disease progression .
our findings oppose the study of lang et al . , which reported a greater decline in m - edl in comparison to nm - edl based on mds - updrs parts i and ii . this study had a longer follow - up period ( up to 5 years ) and only included subjects with pd in early stages .
it is possible that discrepancy is the result of a shorter follow - up and the inclusion of subjects with varying degrees of severity .
more important is the fact that patients in our study received the best medical treatment in comparison to untreated patients enrolled in a randomized clinical trial setting . as such , our study provides a pragmatic view of the effectiveness of interventions in real - life practice .
it should be highlighted that mds - updrs part i and nmss total scores had a high correlation coefficient , but the mds - updrs part i failed to show any statistically significant difference .
reported a strong convergent validity between mds - updrs part i and nmss but also a lack of concordance in patients with a high burden of nonmotor symptoms .
although it is expected that mds - updrs scores correlate with the disease duration , the patients assessed in our study had different pd durations . while this issue affects direct extrapolation , it also gives a more objective overview of daily clinical practice .
secondly , patients had different therapeutic schemes at the initial evaluation ; thus final outcomes could be influenced by the optimization of the treatment rather than from disease progression . finally ,
as mentioned before , all scales were applied during patients '  on  clinical state in order .
this might not reflect the natural history of the disease and therapeutic effect should be considered . on the other hand , nonmotor symptoms did not change with treatment as much as motor scores . also , nonmotor fluctuations were not assessed . in conclusion , we found a motor improvement during the 21-month follow - up accompanied by an increase in motor complications .
studies assessing motor and nonmotor changes over time in different stages of severity are needed .
 
 background . 
 parkinson 's disease ( pd ) is a chronic and progressive disorder . 
 rates of change in motor symptoms have been more studied compared to nonmotor symptoms . 
 the objective was to describe these changes in a real - life cohort of subjects with pd . methods . 
 a cohort study was carried out from 2011 to 2013 . 
 consecutive patients with pd were recruited from a movement disorders clinic . 
 mds - updrs , pdq-8 , and nmss were applied to all subjects at an initial evaluation and a subsequent visit ( 21  3 months ) . 
 disease severity was categorized using a recent classification of mds - updrs severity 
 . results . 
 the mds - updrs part iii showed a significant decrease of 7.2  2.31 points ( p = 0.001 ) between evaluations . 
 a mean increase of 0.9  0.6 points ( p = 0.015 ) in the mds - updrs part iv was observed . 
 an increase of 14.3  11.4 points ( p = 0.043 ) in the nmss total score was found ; when assessed individually , the difference was statistically significant only for the perceptual problems / hallucinations item . 
 quality of life remained unchanged . 
 conclusion . 
 motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization . 
 nonmotor symptoms worsened as a whole . 
 the overall effect in the quality of life was negligible . 