Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

BACKGROUND: Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. METHODS: Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. RESULTS: Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. CONCLUSION: Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Spatial learning deficits in Parkinson's disease with and without mild cognitive impairment.

BACKGROUND: Several MRI studies have demonstrated hippocampal atrophy in Parkinson's disease (PD), a structure considered a key element in spatial learning. Despite this, no study has been undertaken to investigate spatial navigation in PD using a virtual version of the Morris water maze, which is the gold standard for testing hippocampal function in rodents. METHODS: We studied 17 cognitively unimpaired PD patients, 12 PD patients with mild cognitive impairment (MCI) and 15 controls in a virtual water maze procedure. RESULTS: Measured by the main outcome parameters latency to locate the target and heading error (average difference between direction of movement toward anticipated target and real direction toward the target), controls performed significantly better on the virtual water maze task than cognitively unimpaired PD patients or PD patients with MCI, while there was no significant difference between latter two groups. CONCLUSIONS: The virtual water maze test differentiates PD patients from controls, but does not distinguish between cognitively normal and cognitively impaired PD patients, indicating a possible dopamine dependent component in spatial learning. Spatial performance deficits might thus constitute very early signs of dopamine depletion independent of the presence of MCI in Parkinson's disease.

Quantitative assessment of non-motor fluctuations in Parkinson's disease using the Non-Motor Symptoms Scale (NMSS).

Data on frequency, severity and correlations of NMS with motor complications are only available for a limited number of NMS. The NMS Scale (NMSS) is a validated tool to assess a broad range of NMS, which has not been used in NMS fluctuations. We assessed fluctuations of a broad range of non-motor symptom (NMS) for a 1-month time period in fluctuating Parkinson's disease (PD) in a multicenter cross-sectional study using the NMSS assessing NMS in motor On (NMSSOn) and Off state (NMSSOff) combined with clinical NMS and motor function scoring in 100 fluctuating PD patients. ΔNMSSOn/Off was defined as the differences of NMSS scores between On and Off. Complete NMSS datasets were available from 73 patients (53 % men; age: 68.2 ± 9.7 years) with mean total NMSS score in On state of 41.5 ± 37.6 and in Off state of 75.6 ± 42.3 (P < 0.001). Scores were higher in Off compared to On state for all domains except for domain "perceptual problems/hallucinations" (P = 0.608). Clinimetric properties of the NMSS were similar to those reported previously for NMS assessments independent of motor oscillations. NMSSOn, NMSSOff and ΔNMSSOn/Off showed weak to moderate correlations with demographics, indicators of motor symptom severity as well as with other measures of NMS, depression and quality of life. Correlations of NMSS items/domains with independent measures of related constructs were weak to moderate. In conclusion, when assessed with the NMSS, a broad range of NMS fluctuate with motor oscillations, but these fluctuations do neither correlate with motor function nor with measures of disease progression.

Speech Prosody Across Stimulus Types for Individuals with Parkinson's Disease.

BACKGROUND: Up to 89% of the individuals with Parkinson's disease (PD) experience speech problem over the course of the disease. Speech prosody and intelligibility are two of the most affected areas in hypokinetic dysarthria. However, assessment of these areas could potentially be problematic as speech prosody and intelligibility could be affected by the type of speech materials employed. OBJECTIVE: To comparatively explore the effects of different types of speech stimulus on speech prosody and intelligibility in PD speakers. METHODS: Speech prosody and intelligibility of two groups of individuals with varying degree of dysarthria resulting from PD was compared to that of a group of control speakers using sentence reading, passage reading and monologue. Acoustic analysis including measures on fundamental frequency (F0), intensity and speech rate was used to form a prosodic profile for each individual. Speech intelligibility was measured for the speakers with dysarthria using direct magnitude estimation. RESULTS: Difference in F0 variability between the speakers with dysarthria and control speakers was only observed in sentence reading task. Difference in the average intensity level was observed for speakers with mild dysarthria to that of the control speakers. Additionally, there were stimulus effect on both intelligibility and prosodic profile. CONCLUSIONS: The prosodic profile of PD speakers was different from that of the control speakers in the more structured task, and lower intelligibility was found in less structured task. This highlighted the value of both structured and natural stimulus to evaluate speech production in PD speakers.

Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications.

OBJECTIVE: To evaluate frequency, severity, and correlation of nonmotor symptoms (NMS) with motor complications in fluctuating Parkinson disease (PD). METHODS: The Multicenter NonMotor Fluctuations in PD cross-sectional study used clinical examination of 10 NMS (dysphagia, anxiety, depression, fatigue, excessive sweating, inner restlessness, pain, concentration/attention, dizziness, bladder urgency) quantified using a visual analogue scale (VAS) in motor-defined on (NMS(On)) and off state (NMS(Off)) combined with motor assessments and self-ratings at home in 100 patients with advanced PD. RESULTS: All NMS except dysphagia, excessive sweating, and bladder urgency fluctuated in conjunction to motor fluctuations with more frequent and severe symptoms in off compared to on state. The proportions of patients experiencing autonomic/sensory NMS in both motor states were similar to those with these NMS exclusively in off state (ratios 0.4-1.3), while for mental/psychic NMS the proportions with exclusive manifestation in off state were higher (ratios 1.8-3.1). Demographic and clinical characteristics correlated neither with NMS frequency patterns and severities nor with ΔNMS(On/Off) severities (defined as the differences of VAS scores between on and off). Severities of NMS(on), NMS(Off), and ΔNMS(On/Off) did not correlate with motor function. Presence of anxiety, depression, fatigue, and pain had negative impact on health-related quality of life (HRQOL) measured by Parkinson's Disease Questionnaire-8 scoring independent of their occurrence with respect to motor state. Fluctuations of these NMS but not of fatigue deteriorated HRQOL. CONCLUSION: Patterns of NMS fluctuations are heterogeneous and complex, but psychic NMS fluctuate more frequently and severely. Demographic parameters and motor function do not correlate with NMS or nonmotor fluctuation severities in fluctuating PD.

Utility of the WHO-Five Well-being Index as a screening tool for depression in Parkinson's disease.

Beck depression inventory (BDI-1A) is the gold standard screening tool for Parkinson's disease (PD) depression, but as a result of its complexity, it is of limited suitability as a quick and easy screening device. We, therefore, validate the 5-item WHO-Five Well-being Index (WHO-5) as a screening tool for PD depression. Two hundred thirteen of 215 recruited PD patients (99.1%) completed the WHO-5. Receiver operating characteristic plots were used to calculate sensitivity/specificity for all cut-off scores for the detection of depression and combined depression/dysthymia as assessed by an independent investigator using the Mini International Neuropsychiatric Interview (MINI). Internal consistency of the WHO-5 was good (Cronbach's alpha = 0.83). WHO-5 showed high validity with adequate detection of depression without differences in the validity indices compared to BDI-1A (P = 0.234). The optimal cut-off value for detection of depression was 12 of 13 points. WHO-5 is a useful, brief, and easy instrument for identifying PD subjects with depression in daily practice.

Pupillary responses to intranasal trigeminal and olfactory stimulation.

The aim of the present study was to investigate whether pupillary responses to odorous stimuli reflect their intensity or hedonic tone. A total of 21 healthy subjects participated in the study. Using a computer-controlled olfactometer, subjects received intranasal stimuli including odors of rose (PEA; 2 concentrations), lemon and rotten eggs, plus the trigeminal irritant CO2 (also at two concentrations). Changes in the pupil diameter were obtained ipsilaterally to the side of stimulus presentation. Both trigeminal and olfactory stimulation produced an increase in pupillary diameter. Latencies for pupillary reaction were fastest for the higher concentration of CO2 and slowest after the presentation of PEA at the low concentration. Response amplitudes were largest in response to stimulation with CO2 at the high concentration, while they were smallest in response to odorous stimulation with PEA. Response latencies decreased with increasing stimulus intensity. No such correlation was found for hedonic ratings and pupillary reactions. Thus, the change in the pupillary diameter indicates differences between stimulus modalities and stimulus strength, but not pleasantness or unpleasantness of the odors.