Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease

Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mds.21507

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Objective—To describe a clock drawing task (CLOX) designed to elicit executive impairment and discriminate it from non-executive constructional failure. Subjects—90 elderly subjects were studied (45 elderly and well persons from the independent living apartments of a continuing care retirement community and 45 patients with probable Alzheimer’s disease). The clock drawing performance of elderly patients was compared with that of 62 young adult controls. Methods—Subjects received the CLOX, an executive test (EXIT25), and the mini mental state examination (MMSE). The CLOX is divided into an unprompted task that is sensitive to executive control (CLOX1) and a copied version that is not (CLOX2). Between rater reliability (27 subjects) was high for both subtests. Results—In elderly subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=˛0.83 v the EXIT25; CLOX2:r=0.85vthe MMSE). EXIT25 and MMSE scores predicted CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R 2 =0.71). The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly contributed to CLOX2 scores (F(4,72)= 57.2, p<0.001; R 2 =0.74). CLOX subscales discriminated between patients with Alzheimer’s disease and elderly controls (83.1% of cases correctly classified; Wilkes’ lambda=0.48, p<0.001), and between Alzheimer’s disease subgroups with and without constructional impairment (91.9% of cases correctly classified; Wilkes’ lambda=0.31, p<0.001). Conclusions—The CLOX is an internally consistent measure that is easy to administer and displays good inter-rater reliability. It is strongly associated with cognitive test scores.The pattern of CLOX failures may discriminate clinical dementia subgroups. (J Neurol Neurosurg Psychiatry 1998;64:588‐594)

https://jnnp.bmj.com/content/jnnp/64/5/588.full.pdf

CLOX: an executive clock drawing task

Dementia affects about 40% of patients with Parkinson's disease; the incidence of dementia in these patients is up to six times that in healthy people. Clinically, the prototype of dementia in PD is a dysexecutive syndrome. Loss of cholinergic, dopaminergic, and noradrenergic innervation has been suggested to be the underlying neurochemical deficits. Nigral pathology alone is probably not sufficient for the development of dementia. Although there is some controversy with regard to the site and type of pathology involved, dementia is likely to be associated with the spread of pathology to other subcortical nuclei, the limbic system, and the cerebral cortex. On the basis of more recent studies, the main pathology seems to be Lewy-body-type degeneration with associated cellular and synaptic loss in cortical and limbic structures. Alzheimer's disease-type pathology is commonly associated with dementia but less predictive. Recent evidence from small studies suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(03)00351-X.pdf

Dementia associated with Parkinson's disease

Objective – Dementia occurs frequently in patients with Parkinson’s disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia.



Methods –  Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied.



Results –  The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters.



Interpretation –  Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Dementia in Parkinson’s disease: diffusion tensor imaging

Pathophysiology of hallucinations in Parkinson's disease is poorly understood. This study investigated relationships between visual hallucinations and visual acuity. Twenty-six consecutive patients with Parkinson's disease participated in this study. Patients were divided into two groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). Unaided and corrected eyesight was evaluated in all patients, and if frequent use of prescription glasses or contact lenses was involved, eyesight using these lenses was also measured as the patient's own best eyesight. If a patient did not use prescription glasses or contact lenses, the patient's own best eyesight was defined as the unaided eyesight. Multivariate regression analysis demonstrated that agonist use and best eyesight were different after the backward elimination method. Visual hallucinations were closely related not to uncorrected eyesight or unaided eyesight but to the patient's best eyesight. It is suggested that impaired visual acuity is a risk factor for visual hallucinations.

Impaired visual acuity as a risk factor for visual hallucinations in Parkinson's disease.

Dementia in Parkinson's disease is thought to be attributable not only to subcortical lesions but also to cortical alterations, especially frontal lobe dysfunction. To evaluate cortical function, the regional cerebral blood flow (rCBF) was estimated of 13 demented and 13 non-demented age matched patients with Parkinson's disease compared with that of 10 age matched controls using I-123 iodoamphetamine single photon emission tomography (IMP-SPECT). The rCBF of the nondemented Parkinson's patients showed no significant differences from that of the control subjects. In the demented patients, the bilateral frontal and parietal and left temporal regional blood flow was significantly less than in the controls. Four demented patients showed isolated frontal hypoperfusion, 8 showed fronto-parietal hypoperfusion, and 1 showed isolated parietal hypoperfusion. Frontal hypoperfusion was therefore present in 12 of the 13 demented patients, and this finding agrees with the frontal lobe dysfunction hypothesis. Parietal rCBF had a significant positive correlation with cortical functions such as calculation and language ability in the MMSE scores. The parietal and temporal reduction in rCBF probably reflects the presence of Alzheimer pathology, cortical Lewy body disease, or both.

https://jnnp.bmj.com/content/jnnp/55/10/960.full.pdf

SPECT findings in Parkinson's disease associated with dementia.

The pathophysiology of depression and anxiety in Parkinson’s disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson’s disease (PD) patients with and without depression to investigate the nature of depression in PD. Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.

Depression in Parkinson's disease. Diffusion tensor imaging study.

Little is known about the developing mechanisms of visual hallucinations in Parkinson's disease. This study aimed to investigate perfusion changes in parkinsonian patients with visual hallucinations using n-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) single photon emission computed tomography imaging. A total of 70 consecutive patients, including 31 patients with visual hallucinations, and 39 patients without hallucinations, participated in this study. Patients with severe cognitive impairment (Mini-Mental State Examination score < 20), nonvisual hallucinations, or confusion were excluded. We compared brain perfusion changes between the two groups. We found that hallucinatory patients had significant perfusion reductions in the bilateral inferior parietal lobule, inferior temporal gyrus, precuneus gyrus, and occipital cortex compared to nonhallucinatory patients. These results suggested that hypoperfusion of the visual pathway was closely related to visual hallucinations in Parkinson's disease. © 2006 Movement Disorder Society

Kazuto Nishinaka

Papers

Dementia in Parkinson’s disease: diffusion tensor imaging

Impaired visual acuity as a risk factor for visual hallucinations in Parkinson's disease.

SPECT findings in Parkinson's disease associated with dementia.

Depression in Parkinson's disease. Diffusion tensor imaging study.

Hypoperfusion of the visual pathway in parkinsonian patients with visual hallucinations.