Whole-brain proton MR spectroscopic imaging in Parkinson's disease.

BACKGROUND AND PURPOSE: To examine the distributions of proton magnetic resonance spectroscopy (MRS) observed metabolites in Parkinson's disease (PD) throughout the whole brain. METHODS: Twelve PD patients and 18 age-matched controls were studied using neuropsychological testing, MRI and volumetric MR spectroscopic imaging. Average values of signal normalized metabolite values for N-acetyl-aspartate, total-creatine, and total-choline (NAA, total-Cre, total-Cho, respectively) and their ratios were calculated for gray matter (GM) and white matter (WM) in each lobar brain region. RESULTS: Analyses revealed altered metabolite values in PD subjects relative to controls within the GM of the temporal lobe (right: elevated Cre, P = .027; decreased NAA/Cre, P = .019; decreased Cho/Cre, P = .001 and left: decreased NAA/Cre; P = .001, decreased Cho/Cre, P = .007); the right occipital lobe (decreased NAA, P = .032 and NAA/Cre, P = .016); and the total cerebrum GM (decreased NAA/Cre, P = .029). No meaningful correlations were obtained between abnormal metabolite values and the neuropsychological measures. CONCLUSIONS: PD is associated with widespread alterations of brain metabolite concentrations, with a primary finding of increased creatine. Higher creatine values in our PD sample may reflect greater neuronal energy expenditure early in the disease process that is compensatory. This is the first whole brain MRS study of PD that has examined metabolite changes across a large fraction of the brain volume, including the cortical mantle.

An accelerometry-based study of lower and upper limb tremor in Parkinson's disease.

Over the past two decades, several studies have aimed to quantify the kinetic properties of tremor with primary focus on the upper limbs. However, there is a lack of investigation into the properties of tremor in the lower limbs. The objective of this preliminary study was to investigate the properties of oscillatory movement, at rest and in posture, in both the upper and lower limbs of Parkinson's disease (PD) patients with clinically undetectable to modest rest/postural tremor and healthy controls. PD patients (N = 16) and controls (N = 8) were examined clinically by a movement disorders specialist and oscillatory movements in all four extremities were evaluated using a portable biaxial accelerometer. While tremor intensity and frequency did not differ between groups, the intraindividual variability of rest and postural tremor frequency in the dexterity-dominant lower limb was lower in people living with PD than in healthy adults. Additionally, rest tremor frequency was discrepant between upper and lower limbs in PD. Our work introduces the possibility that minute variations in lower limb movements, which are imperceptible upon expert clinical exam, can be used to differentiate a diseased sample from a healthy one. These preliminary findings suggest that additional work using objective tremor measurement may improve our understanding of lower limb motor dysfunction in PD and lead to the refinement of current, and the development of new, metrics to enhance early diagnosis, differential diagnosis, and symptom quantification.

Objective quantification of neuromotor symptoms in Parkinson's disease: implementation of a portable, computerized measurement tool.

Quantification of neuromotor symptoms with device-based measures provides a useful supplement to clinical evaluation. Research using the CATSYS has established its utility as a computerized measurement system to quantify neuromotor function. The primary objective of this study is to provide technical guidance on the use of the CATSYS in Parkinson's disease (PD). Forty-four patients with idiopathic PD and 28 healthy controls were prospectively recruited and evaluated with CATSYS, a portable, Windows-based system consisting of a data logger and four different sensors (tremor pen, touch recording plate, reaction time handle, and force plate for balance recording) for quantification of neuromotor functions. CATSYS discriminated between PD and controls on measurements of rest/postural tremor, pronation/supination, finger tapping, simple reaction time, and postural sway intensity and velocity. CATSYS measurements using the proposed test battery were associated with relevant clinician-rated Unified Parkinson's disease rating scale (UPDRS) items assessing tremor and bradykinesia. More work is warranted to establish CATSYS as a diagnostic/monitoring instrument in movement disorders using the proposed technical approaches.

Subthreshold depression in Parkinson's disease.

OBJECTIVE: It is estimated that 40% of patients with Parkinson's disease (PD) are clinically depressed, however, little is known about the frequency and associated features of subthreshold depression in PD. The current study sought to determine the prevalence of subthreshold depression (sD) and to further characterize the associated features in a sample of 111 nondemented patients with moderate to severe PD. METHODS: Patients were classified into the following groups: diagnostic depression (DD), subthreshold depression (sD), or nondepressed (ND) by applying the Diagnostic and Statistical Manual, 4th edn criteria for depression and previously reported criteria for sD to items from the Beck Depression Inventory, 2nd edn. These groups were compared on clinical and demographic variables. The symptom profile of the sD group is also described. RESULTS: Fifty participants (45.0%) were classified as ND, 32 (28.8%) as sD, and 29 (26.1%) as DD. Patients with sD were younger (approximately 5 yrs) than nondepressed patients, but did not differ in disease stage or any other demographic variables. Patients with sD tended to endorse mood symptoms that overlap with PD, including fatigue, sleep difficulties, appetite dysfunction, and concentration difficulties. These symptoms were also endorsed with high frequency by the other groups. CONCLUSIONS: These findings suggest that sD is not uncommon in PD and may be more prevalent among younger patients. The finding that sD patients report mood symptoms that overlap with the PD symptomatology suggests that these two entities share common features and may be difficult to disentangle.

Features of gait most responsive to tap test in normal pressure hydrocephalus.

OBJECTIVE: To identify components of gait associated with a positive tap test (TT) in patients with idiopathic normal pressure hydrocephalus (iNPH). PATIENTS AND METHODS: Thirty-three patients with iNPH underwent clinical evaluation pre- and post-TT and were classified as responders (Rs) or non-responders (NRs). Elements of gait were assessed with a formal standardized Gait Scale and compared between groups. RESULTS: Analysis of pre/post-TT group differences revealed an interaction for Total Gait Score and Walking Score, with improvements in responders only. Total Gait Scores improved by 29% in the Rs and 4.85% in the NRs. Rs showed significant post-TT improvements on a timed 10m walk, turning, and balance. Tandem walking, turning, truck balance and start stop hesitation showed trends toward improvement. CONCLUSIONS: The classic features of gait often used in determining diagnosis of NPH (wide based stride, reduced foot-floor clearance, and small steps) were not helpful in identifying responders to the TT. Walking speed, steps for turning, and tendency towards falling were most likely to improve post-TT. These straightforward measures can readily be adapted into clinical practice to assist in determination of shunt candidacy.

Side and type of motor symptom influence cognition in Parkinson's disease.

It is well known that many patients with Parkinson's disease experience neuropsychological decline. However, the nature and extent of mental status change varies widely, with some patients showing mild or no cognitive impairments and others exhibiting frank dementia. Research has shown that several clinical disease parameters may differentially correlate with patterns of neuropsychological dysfunction. The present study examined side and type of motor symptom at disease onset and their relationship to cognition in idiopathic Parkinson's disease (PD). We identified 58 patients who initially presented with one of the following symptom profiles: right-side tremor onset (RSO-T; n = 15), right-side bradykinesia/rigidity onset (n = 12), left-side tremor onset (n = 19), and left-side bradykinesia/rigidity onset (n = 12). There were no differences between groups in disease duration, overall mental status, education, or depression severity. We administered a battery of neuropsychological measures to the four PD subgroups and a group of matched control subjects (n = 40). MANCOVAs controlling for age revealed patients with RSO-T performed significantly better than the other three PD subgroups across the entire neuropsychological battery. Further, the RSO-T subgroup performed comparably to controls. In contrast, the other three PD subgroups showed widespread cognitive deficits. These findings suggest an intricate relationship between motor symptom and side of disease onset and it is the combination of these factors that may influence the disease course and extent of cognitive deterioration. Furthermore, patients who develop tremor on the right side of their body represent a distinct subgroup of PD patients who exhibit relative sparing of cognitive function.

Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease.

Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, ample evidence exists that specific cognitive changes occur early in the course of PD. This evidence does not imply that cognitive deficits are pervasive during the early stages. To the contrary, they are usually subtle and often difficult to detect without formal neuropsychological testing. Executive-function deficits are the most frequently reported cognitive problems and, given that executive skills are an integral part of many tasks, it follows that subtle difficulties may be seen on a wide range of cognitive measures, particularly in working memory and visuospatial dysfunction, two areas that rely heavily on executive skills. Whereas apraxia and language processing deficits occur infrequently, subtle changes in olfaction and contrast sensitivity have also been repeatedly observed. Finally, depressive symptoms are also common in the early stages of the disease. The significance of the early behavioral changes and their prognostic implications are largely unknown. Prospective studies are needed to understand the longitudinal course of early cognitive changes to determine whether they remain as circumscribed impairments or represent a precursor to a more widespread dementia.