Changes in motor subtype and risk for incident dementia in Parkinson's disease

Haukeland University Hospital, Bergen, Hordaland, Norway
Movement Disorders (Impact Factor: 5.68). 08/2006; 21(8):1123 - 1130. DOI: 10.1002/mds.20897


The objective of this study was to assess the temporal relationship between changes in predominant motor symptoms and incident dementia in Parkinson's disease (PD). A community-based sample of 171 nondemented patients with PD was followed prospectively and examined at baseline and after 4 and 8 years. The motor subtype of Parkinsonism was classified into tremor-dominant (TD), indeterminate, or postural instability gait difficulty (PIGD) subtype at each visit, based on defined items in the Unified Parkinson's Disease Rating Scale, subscales II and III. Dementia was diagnosed according to DSM-III-R criteria, based on clinical interview, cognitive rating scales, and neuropsychological examination. Logistic regression was used to analyze the relationship between subtype of Parkinsonism and dementia. Transition from TD to PIGD subtype was associated with a more than threefold increase in the rate of Mini-Mental State Examination decline. Compared to patients with persistent TD or indeterminate subtype, the odds ratio for dementia was 56.7 (95% CI: 4.0–808.4; P = 0.003) for patients changing from TD or indeterminate subtype to PIGD subtype, and 80.0 (95% CI: 4.6–1400.1; P = 0.003) for patients with persistent PIGD subtype. Patients with TD subtype at baseline did not become demented until they developed PIGD subtype, and dementia did not occur among patients with persistent TD subtype of Parkinsonism. In a substantial proportion of PD patients who develop postural instability and gait disorder during the course of the disease, this transition is associated with accelerated cognitive decline and highly increased risk for subsequent dementia. These findings raise the question whether PIGD and dementia share common or parallel neuropathology. © 2006 Movement Disorder Society

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    • "The non-tremor dominant motor subtype usually presents a more severe clinical pattern of non-motor symptoms in comparison to the tremor dominant subtype. Since the early untreated stages of PD, this subtype is characterized by a higher risk of MCI (Poletti et al., 2012a) and longitudinally is associated with faster motor worsening (Vu et al., 2012), cognitive decline (Burn et al., 2006), and higher risk of developing dementia (Alves et al., 2006; Sollinger et al., 2010). This subtype is also associated with an increasing risk of developing psychopathological features, including affective features such as depression and alexithymia (Starkstein et al., 1998; Reijnders et al., 2009; Poletti et al., 2011; Burn et al., 2012) and psychotic features as hallucinations (Reijnders et al., 2009). "
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    ABSTRACT: Parkinson's disease (PD) is a neurological disorder, associated with rigidity, bradykinesia, and resting tremor, among other motor symptoms. In addition, patients with PD also show cognitive and psychiatric dysfunction, including dementia, mild cognitive impairment (MCI), depression, hallucinations, among others. Interestingly, the occurrence of these symptoms-motor, cognitive, and psychiatric-vary among individuals, such that a subgroup of PD patients might show some of the symptoms, but another subgroup does not. This has prompted neurologists and scientists to subtype PD patients depending on the severity of symptoms they show. Neural studies have also mapped different motor, cognitive, and psychiatric symptoms in PD to different brain networks. In this review, we discuss the neural and behavioral substrates of most common subtypes of PD patients, that are related to the occurrence of: (a) resting tremor (vs. nontremor-dominant); (b) MCI; (c) dementia; (d) impulse control disorders (ICD); (e) depression; and/or (f) hallucinations. We end by discussing the relationship among subtypes of PD subgroups, and the relationship among motor, cognitive, psychiatric factors in PD.
    Frontiers in Systems Neuroscience 12/2013; 7:117. DOI:10.3389/fnsys.2013.00117
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    • "A recent study also showed how PIGD symptoms are apparently associated with gray matter atrophy in motor related regions [20]. Recent studies have also shown that some patients may eventually switch from the TD type to the PIGD type, when the disease progresses and that this switch may be associated with the development of dementia [21]. In this context, the possibility of distinguishing between the two motor subtypes in an easy and reliable way is becoming increasingly relevant. "
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    ABSTRACT: In this study, the use of an instrumented balance test based on inertial sensors was evaluated in patients with Parkinson's disease (PD). We aimed to objectively characterize motor subtypes of PD (tremor dominant, TD and postural instability gait difficulty, PIGD), to help to quantitatively classify the PD subjects into motor subtypes. Subjects were studied performing postural tests, while wearing a device including a tri-axial accelerometer on the lower back, in four different experimental conditions that depended on feet position (feet-together or semi-tandem) and vision (eyes open or closed). Postural measures, after a reliability check, were tested to identify their sensitivity to the disease, to the PD subtypes, and to the experimental conditions. The results highlight the possibility of distinguishing between the TD and PIGD subtypes by means of objective postural measures that are able to detect tremor and PIGD features and are able to classify a subject as TD or PIGD with good accuracy. Feet position influences frequency measures, whereas eyes closure influences the displacement measures and enhances differences between PD and control subjects, suggesting that postural displacement measures may be capable of detecting different adaptation processes to external sensory conditions between patients with PD and control subjects.
    IEEE transactions on neural systems and rehabilitation engineering: a publication of the IEEE Engineering in Medicine and Biology Society 12/2013; 22(5). DOI:10.1109/TNSRE.2013.2292496 · 3.19 Impact Factor
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    • "This approach rests on the notion that TD and AR subtypes reflect different points on a continuum. Indeed, some patients who initially present with one motor phenotype can later develop features of the other (albeit predominantly from TD to AR, rather than the reverse) [32] which argues against AR and TD being two discrete entities. "
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    ABSTRACT: In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease.
    Parkinsonism & Related Disorders 08/2013; 19(12). DOI:10.1016/j.parkreldis.2013.08.011 · 3.97 Impact Factor
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