Akinori Futamura

Dysfunctional counting of mental time in Parkinson's disease.

Patients with Parkinson’s disease (PD) often underestimate time intervals, however it remains unclear why they underestimate rather than overestimate them. The current study examined time underestimation and counting in patients with PD, in relation to dopamine transporter (DaT) located on presynaptic nerve endings in the striatum. Nineteen non-dementia patients with PD and 20 age- and sex-matched healthy controls performed two time estimation tasks to produce or reproduce time intervals with counting in the head, to examine dysfunctional time counting processing. They also performed tapping tasks to measure cycles of counting with 1 s interval with time estimation. Compared to controls, patients underestimated time intervals above 10 s on time production not reproduction tasks, and the underestimation correlated with fast counting on the tapping task. Furthermore, striatal DaT protein levels strongly correlated with underestimation of time intervals. These findings suggest that distortion of time intervals is guided by cumulative output of fast cycle counting and that this is linked with striatal DaT protein deficit.

Correlation between motor and cognitive functions in the progressive course of Parkinson's disease

Correlations between motor function and frontal‐executive function in Parkinsons disease (PD) have been examined previously, but correlations with other cognitive domains remain unknown. We examined the correlation between motor dysfunction and cognitive impairment with regard to their precise domains.

Picture agnosia as a characteristic of posterior cortical atrophy.

Background: Posterior cortical atrophy (PCA) is a degenerative disease characterized by progressive visual agnosia with posterior cerebral atrophy. We examine the role of the picture naming test and make a number of suggestions with regard to diagnosing PCA as atypical dementia. Methods: We investigated 3 cases of early-stage PCA with 7 control cases of Alzheimer disease (AD). The patients and controls underwent a naming test with real objects and colored photographs of familiar objects. We then compared rates of correct answers. Results: Patients with early-stage PCA showed significant inability to recognize photographs compared to real objects (F = 196.284, p = 0.0000) as measured by analysis of variants. This difficulty was also significant to AD controls (F = 58.717, p = 0.0000). Conclusion: Picture agnosia is a characteristic symptom of early-stage PCA, and the picture naming test is useful for the diagnosis of PCA as atypical dementia at an early stage.

perceiving "ghost" images: a unique case of visual allesthesia with hemianopsia in mitochondrial disease

A 49-year-old man with mitochondrial disease presented with visual allesthesia, a rare and puzzling phenomenon. He was admitted for treatment because of convulsions. After the convulsions ceased, he exhibited left homonymous hemianopsia. Brain diffusion-weighted magnetic resonance imaging (MRI) showed a high-intensity area in the right occipital lobe. Both the hemianopsia and the MRI activation in this area disappeared by day 36 of hospitalization. On the morning of day 57, right homonymous hemianopsia emerged in a singular manner. The patient perceived an illusory object (a bottle placed by the bedside) in his left visual field, while the real object was in his blind right field. This case of visual allesthesia was accompanied by palinopsia, ie, perseveration of the image of the bottle. Diffusion-weighted MRI showed a new, high-intensity area in the left occipital lobe. We believe the visual allesthesia resulted from transfer of cortical information obtained by blindsight between hemispheres as a result of epileptic excitation.

The Montreal Cognitive Assessment and Neurobehavioral Cognitive Status Examination are useful for screening mild cognitive impairment in Japanese patients with Parkinson's disease

Diagnosis of mild cognitive impairment (MCI) in Parkinsons disease (PD; PD‐MCI) can be difficult. We examined whether the Japanese version of the Montreal Cognitive Assessment (MoCA‐J) and the Neurobehavioral Cognitive Status Examination (COGNISTAT‐J) were suitable to screen PD‐MCI.

Modified Six Elements Test: Earlier diagnosis of the correlation between motor and executive dysfunction in Parkinson's disease without dementia

In patients with Parkinsons disease, executive deficits are known to correlate with motor dysfunctions, such as gait and postural instability. However executive deficits are sometimes difficult to detect using common frontal assessment batteries. Behavioral Assessment of Dysexecutive Syndrome includes six subtests to evaluate different aspects of executive function required in daily life. Among these the Modified Six Elements Test examines higher levels of executive function with regard to prospective memory and organization of behavior.

Diabetes and Dementia

An aging global population is driving the current epidemic of dementia and type 2 diabetes mellitus. Diabetes is a known risk factor for the development of vascular dementia, Alzheimers disease, and mild cognitive impairment. Good control of diabetes may improve cognitive decline and prevent Alzheimers disease. Mild cognitive impairment with type 2 diabetes (DM-MCI) often presents as a decline in attention, psychomotor speed, executive function, and memory. The Montreal Cognitive Assessment (MoCA) is one of the best screening tools for detecting DM-MCI. We found that 72% of the patients admitted to educational hospitalization for type 2 diabetes could also be categorized into groups with frontal lobe dysfunction, delayed recall, and a mixed-type group. Anti-diabetic drugs and insulin may protect and improve cognitive dysfunction in Alzheimers disease and DM-MCI, but more studies are needed to verify this claim. Diabetes mellitus may be linked not only to Alzheimers disease but also to other neurodegenerative diseases, such as Parkinsons, Huntingtons and frontotemporal lobe dementia.

Spatial distortion related to time compression during spatiotemporal production in Parkinson's disease

&NA; To produce coordinated manual actions within specific space and time, their relationship must be properly dealt with in a sensorimotor system. This study examined how such a coordination system might be impaired in normal aging and in Parkinsons disease (PD). Using a tablet device, young participants, elderly participants, and patients with PD were tested for concurrent production of distance and duration as well as single production of distance or duration alone. Results were analyzed in relation to deficiency of presynaptic dopamine transporter (DaT) in the striatum. We observed different patterns of impairment between normal aging and PD. Elderly participants exhibited duration overproduction when they had to produce distance and duration concurrently, but were normal in single production of either distance or duration. In contrast, PD patients exhibited normal distance production and marked underproduction of duration when either distance or duration was produced alone, but both duration and distance were underproduced when they were concurrently produced. These findings suggest that aging yields impaired performances in both elderly people and PD patients, but that temporal underproduction in PD patients entrains spatial production as if the distance to be produced were made consistent with their duration underproduction. We also observed that striatal DaT deficit was correlated with the extent of duration underproduction in PD patients. The deficit may be associated with the severe time compression and the entrainment during spatiotemporal production in PD patients. HighlightsUsing a tablet, we examined spatiotemporal production in Parkinsons disease (PD).PD exhibited normal distance and underproduced duration in single production.The duration in PD entrained spatial production during spatiotemporal processing.The duration and the entrainment were linked to dopamine transporter deficit in PD.

Accumulation of 123I-Ioflupane Is a Useful Marker of the Efficacy of Selegiline Monotherapy in Drug-Naïve Parkinson’s Disease

Background: Selegiline enhances the patient’s endogenous dopamine by inhibiting dopamine metabolism. The efficacy of selegiline monotherapy for drug-naïve Parkinson’s disease (PD) patients may depend on the degree of dopaminergic neuronal degeneration. 123I-Ioflupane single photon emission computed tomography (SPECT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy are diagnostic methods to assess the pharmacological and pathological changes in PD. Objective: We examined the utility of these imaging methods to predict the efficacy of selegiline monotherapy for motor symptoms in drug-naïve PD patients. Methods: We observed the efficacy of selegiline monotherapy in 28 drug-naïve PD patients and compared the improvement in motor function and the imaging findings. These patients received selegiline monotherapy, and the amount was increased to the optimal dose in clinical practice. Motor function was assessed using the Unified Parkinson’s Rating Scale (UPDRS) at baseline and at the stable dose. Imaging was performed before treatment, and the striatal Specific Binding Ratio (SBR) of the 123I-Ioflupane SPECT and the Heart-to-Mediastinum (H/M) ratio of the 123I-MIBG myocardial scintigraphy were calculated. Both ratios were compared with improvements in scores for motor assessment using Pearson’s correlation coefficient. Results: The mean UPDRS part III score significantly improved with at least 5.0 mg/day of selegiline. Further dose escalation did not improve the mean motor score. The percent improvement in the motor score from baseline showed a significant negative correlation with the SBR of average of the right and left striatum, but not with the H/M ratio. Multiple regression analysis using patient’s background factors showed that percent improvement in the UPDRS part III score directly correlate with the SBR (p = 0.04), but not with the age (p = 0.72), disease duration (p = 0.31), baseline UPDRS part III (p = 0.77) and the drug dose (p = 0.26). Conclusion: PD patients with a lower accumulation of 123I-Ioflupane in the striatum can have greater improvement with selegiline monotherapy.

Improvement in Language Function Correlates with Gait Improvement in Drug-naïve Parkinson’s Disease Patients Taking Dopaminergic Medication

BACKGROUND Dopaminergic drugs, the gold standard for motor symptoms, are known to affect cognitive function in Parkinsons disease (PD) patients. OBJECTIVE We compared the effects of dopaminergic treatment on motor and cognitive function in drug-naïve patients. METHODS Dopaminergic medication (levodopa, dopamine agonist, selegiline) was given to 27 drug-naïve PD patients and increased to a dose optimal for improved motor symptoms. Patients were tested prior to, and 4-7 months after, drug initiation. Motor function was assessed using the Unified Parkinsons Disease Rating Scale (UPDRS). Cognitive function was assessed using both the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and the Neurobehavioral Cognitive Status Examination (COGNISTAT-J). Improvements from baseline for both motor and cognitive assessment were compared. RESULTS Mean score of all motor assessments (UPDRS total score of Parts II and III, and sub-scores of tremor, rigidity, bradykinesia, gait, and postural instability) and certain cognitive assessments (MoCA-J total score and subscore of delayed recall) significantly improved with dopaminergic medication. Gait score improvement showed significant positive correlation with improvement in MoCA-J language domain and in language-comprehension subtests of COGNISTAT-J using Spearmans correlation coefficients. Furthermore, multiple regression analysis showed gait score improvement significantly correlated with improvements in the subtests of language-comprehension in COGNISTAT-J. CONCLUSION There is correlated improvement in both gait and language function in de novo PD patients in response to dopaminergic drugs. Gait and language dysfunction in these patients may share a common pathophysiology linked to dopamine deficits.