Association of Neuropsychiatric Symptom Profiles With Cognitive Decline in Patients With Parkinson Disease and Mild Cognitive Impairment

Abstract

Background and Objectives:Neuropsychiatric symptoms (NPS) are closely associated with cognitive decline in patients with Parkinson’s disease (PD). We investigated which profiles of NPS are associated with the risk of dementia in PD with mild cognitive impairment (PD-MCI).Methods:We retrospectively assessed 338 patients with PD-MCI from a single tertiary hospital, who underwent neuropsychological tests and a neuropsychiatric inventory (NPI) questionnaire. We conducted a factor analysis of the dichotomized presence of 12 NPI symptoms, yielding three NPI factors: factor 1, mood symptoms; factor 2, hyperactivity-related symptoms; and factor 3, psychotic symptoms. Factor analysis of the severity of NPI symptoms also identified similar NPI factors. The neuropsychiatric correlates of NPI factors were evaluated using general linear models for cognitive tests. Subsequently, we evaluated the hazard ratio (HR) of NPI factors on conversion to dementia.Results:A higher prevalence factor 1 score was associated with lower scores in the verbal memory (β = -0.15; 95% confidence interval [CI] = -0.24 – -0.06;p= 0.001) and executive domains (β = -0.16; 95% CI = -0.28 – -0.04;p= 0.007), whereas higher severity factor 2 scores were associated with lower scores in the naming (β = -0.16; 95% CI = -0.28 – -0.03;p= 0.012), visuospatial (β = -0.24; 95% CI = -0.41 – -0.07;p= 0.005), and verbal memory domains (β = -0.15; 95% CI = -0.24 – -0.05;p= 0.005). A higher severity factor 3 score was associated with lower scores in the visuospatial domain (β = -0.25; 95% CI = -0.46 – -0.07;p= 0.007). Cox regression models demonstrated that the risk of dementia was increased in those with higher prevalence factor 1 (HR = 1.48, 95% CI = 1.17 – 1.88,p= 0.001) and factor 2 scores (HR = 1.27, 95% CI = 1.07 – 1.51,p= 0.007) and severity factor 3 score (HR = 1.52, 95% CI = 1.29 – 1.80,p< 0.001) after adjusting for age, sex, education, disease duration, scores for cognition and parkinsonism, and levodopa equivalent dose.Discussion:This study demonstrated that a higher burden of NPS is associated with dementia conversion in patients with PD-MCI.

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis

“…The association of psychosis with cognitive impairment, death, disease progression, falls or fractures and residential home admission was tested across 21 studies in 159,438 patients. 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 Psychosis was significantly associated with cognitive impairment (SMD 0.44, [95% CI 0.23–0.66], p < 0.0001, I 2 30.9 [ I 2 95% CI 0–48.6]) and disease progression (SMD 0.46, [95% CI 0.12–0.80], p = 0.0078, I 2 70.3% [ I 2 95% CI 13.4–96.9]). There was no significant association with residential home admission (SMD 0.38, [95% CI −1.27 to 2.03], p = 0.65, I 2 0% [ I 2 95% CI 0–95.1]), death (SMD 0.59 [95% CI −0.78 to 1.96], p = 0.40, I 2 0%, [ I 2 95% CI 0–97.7]), or falls/fractures (SMD 0.39 [95% CI −0.77 to 1.56], p = 0.51, I 2 0% [ I 2 95% CI 0–98.7]).…”

“…The association of depression with subsequent cognitive impairment, disease progression, death, disability, falls or fractures and residential home admission was tested across 6324 participants in 29 studies. 18 , 19 , 20 , 21 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 Depression was significantly associated with cognitive impairment (SMD 0.37 [95% CI 0.10–0.65], p = 0.0085, I 2 27.1%, [ I 2 95% CI 0–35.0]), disease progression (SMD 0.46 [95% CI 0.18–0.74], p = 0.0011, I 2 52.2 [ I 2 95% CI 0–81.1]), and disability (SMD 0.42 [95% CI 0.25–0.60], p = <0.0001, I 2 7.9%, [ I 2 95% CI 0–91.2]). There was no significant association for falls or fractures (SMD −0.28 [95% CI −0.90 to 0.34], p = 0.37, I 2 0%, [ I 2 95% CI 0–99.5]) and death (SMD 0.32 [95% CI −0.56 to 1.20], p = 0.47, I 2 0% [ I 2 95% CI 0–37.0]).…”

“…The association of apathy with subsequent cognitive impairment and disease progression was tested across 1332 participants in seven studies. 39 , 40 , 41 , 43 , 65 , 66 , 67 Apathy was significantly associated with cognitive impairment (SMD 0.60 [95% CI 0.02–1.19], p = 0.04, I 2 27.9%, [ I 2 95% CI 0–73.9]). The association between apathy and disease progression was not statistically significant (SMD 0.35 [95% CI −0.16 to 0.85], p = 0.18, I 2 5.7% [ I 2 95% CI 0–95.2]).…”

“…The association of anxiety with subsequent cognitive impairment, disease progression and falls or fractures were tested across 1761 participants in eight studies. 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 There was no significant association found for anxiety with cognitive impairment (SMD 0.41 [95% CI −0.19 to 1.01], p = 0.18, I 2 0%, [ I 2 95% CI 0–77.8]]), there was also no significant association for anxiety and disease progression (SMD −0.27 [95% CI −0.84 to 0.29], p = 0.34, I 2 35.9% [ I 2 95% CI 0–91.4]). The results of the meta-analysis are summarised in Fig.…”