Cristina Prieto-Jurczynska

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and 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 PD.

BACKGROUND: Patients with primary progressive aphasia (PPA) usually develop significant behavioral disturbances with progression of the disease. We tested our clinical observation that development of disruptive agitation is more likely in semantic than in nonfluent PPA and examined which clinical variables could be associated with this behavior. METHODS: We retrospectively analyzed neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n = 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical variables and laterality of temporal atrophy were associated with symptoms in semantic PPA cases. RESULTS: The semantic PPA group developed more frequent (p = 0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly associated with psychotic symptoms (delusions/hallucinations) but was not associated with gender, age at onset, duration of the disease, or laterality of temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed and treated with antidepressants (p = 0.0007). There were no differences in anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor behavior. CONCLUSIONS: Semantic PPA in advanced disease is frequently associated with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent PPA maintains a high prevalence of depression. This implies different treatment and care and support needs for each group.

AIM: To perform an independent evaluation of the psychometric attributes of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS). PATIENTS AND METHODS: The study involved patients with Parkinson's disease (PD) free of any impediments preventing them from participating in the required evaluation. Sociodemographic and historical data were collected for use in this observational, cross-sectional study and the following evaluations were employed: Scales for Outcomes in Parkinson's Disease-Motor Scale (SCOPA-Motor), Hoehn and Yahr staging (HY), Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD), Minimental State Examination (MMSE), SCOPA-Cognitive (SCOPA-Cog), Non-Motor Symptoms Questionnaire and PD-CRS. Acceptability, internal consistence, construct validity and precision of the PD-CRS were analysed. RESULTS: The sample consisted of 50 patients, with a mean age of 63.6 +/- 9.3 years. In all, 66% were males, with a history of 9 +/- 5.7 years with PD, in HY stages 1 to 4. Twelve patients (24%) presented data suggestive of dementia. The PD-CRS score was: sub-cortical sub-scale: 60.9 +/- 16.5; cortical sub-scale: 27.9 +/- 4.4; and total PD-CRS: 88.7 +/- 19.8. The mean-median difference was < 10% of the maximum scores and the total score showed no ceiling or floor effect. Cronbach's alpha was 0.85; the item-total correlations ranged from 0.57 (naming) to 0.73 (working memory), and the homogeneity index of the items was 0.36. Correlation with the MMSE and the SCOPA-Cog was high (rS = 0.53 and 0.77). The PD-CRS score was significantly lower in patients with a low level of schooling and more severe PD according to levels on the CISI-PD and distinguished between patients with and without dementia (70.3 +/- 26.2 versus 94.5 +/- 13; p < 0.001. The standard error of the measurement was 1.98. CONCLUSIONS: The levels of acceptability, internal consistence, construct validity and precision displayed by the PD-CRS were satisfactory.

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.