Dag Aarsland

The Epidemiology of Dementia Associated with Parkinson's Disease

Parkinsons disease (PD) is the second most common neurodegenerative illness after Alzheimers disease (AD). Cognitive impairment and dementia are common features in PD and characterized by a wide range of cognitive deficits distinct from those seen in AD. Mild cognitive impairment occurs even early in PD and is associated with shorter time to dementia. The purpose of this review is to present recent findings on clinical aspects of dementia in PD and to elucidate underlying clinical and neurobiological risk factors.

Executive Dysfunction in Mild Cognitive Impairment is Associated with Changes in Frontal and Cingulate White Matter Tracts

Mild cognitive impairment (MCI) may affect multiple neuropsychological domains. While amnestic MCI is associated with Alzheimers disease, patterns of brain pathology in non-amnestic subtypes have been less studied. Twenty-three patients with attention/executive MCI (a/e MCI), seen at a university-based memory clinic, and 23 normal controls, matched according to age, gender, and education, were included in this study. All subjects were assessed with a neuropsychological test battery, including tests of memory, attention and executive function, and underwent magnetic resonance imaging. Diffusion tensor imaging derived white matter (WM) tract radial and mean diffusivity (DR and MD) were assessed using Tract-Based Spatial Statistics, and cortical thickness (CTH) was assessed using FreeSurfer. This study investigated changes of WM DR/MD and CTH in subjects with a/e MCI, and associations between these changes and different a/e subfunctions. WM DR/MD underlying rostral middle frontal, medial orbitofrontal, caudal anterior cingulate, posterior cingulate, retrosplenial and entorhinal cortices was higher for the a/e MCI than the control group, but CTH was not different from controls in any of the regions. WM DR/MD underlying superior frontal, rostral middle frontal, lateral/medial orbitofrontal and retrosplenial cortices were significantly associated with inhibition/switching performance, while caudal middle frontal CTH was significantly associated with attention and divided attention in the patient group. We conclude that increased WM DR/MD in frontal and cingulate regions and cortical thinning in caudal middle frontal region are both associated with executive dysfunction in MCI.

Nonlinear decline of mini-mental state examination in Parkinson's disease.

The trajectory of cognitive functioning in patients with Parkinsons disease (PD) is not known. We used a random change point model to study the individual cognitive trajectory for up to 15 years in a prevalence sample of 238 PD patients, and used the mini‐mental state examination (MMSE) to assess the longitudinal cognitive course. We observed that the rate of global cognitive decline was nonlinear. Following a relatively stable period, an inflection point was identified, after which the rate of decline gained momentum with an annual decline of 2.8 points on the MMSE. The course was similar in men and women. This inflection point was estimated to occur 13.3 years (95% credible interval 11.8, 13.6) after the diagnosis of PD; however, there were wide interindividual variations in the time from onset of PD to the inflection point.

Rivastigmine for the treatment of Parkinson’s disease dementia

Background: Rivastigmine is licensed for the treatment of Parkinson’s disease dementia (PDD). The aim of the current article is to review the evidence regarding rivastigmine for the treatment of PDD. Three open label studies and one Randomized Controlled Trial (RCT) have been undertaken examining the efficacy of rivastigmine in PDD. In the 24 week RCT, 362 patients were randomised to rivastigmine, and 179 patients to placebo. Significant improvements were seen in cognition, function and global outcome. Nausea affected 29% of patients in the rivastigmine group and 11% of patients in the placebo group, and vomiting was reported by 17% of patients given rivastigmine and 2% of patients given placebo. Emerging or worsening tremor was reported in 10% of patients in the rivastigmine group, compared with 4% in the placebo group. n nConclusion: Rivastigmine is a safe and effective symptomatic treatment for PDD conferring benefits with respect to cognition, function and overall clinical outcome. Further work is needed to establish the comparable efficacy to other cholinesterase inhibitors, the impact on core disease pathology and the potential additive benefits of combination with memantine.

Role of Neuropsychiatric Assessment in Diagnosis and Research

Although the basal ganglia have traditionally been considered as primarily involved in the regulation of motor functioning, their role in the integration of emotions with cognitive and motor behavior is increasingly recognized. Psychiatric symptoms, including disturbance of affect (anxiety and depression), perception (hallucinations), thought (delusions), as well as behavioral and personality changes (apathy and disinhibition) are commonly observed in most basal ganglia diseases. They produce increased suffering and distress both for the patients themselves as well as for the caregivers, and are associated with increased need for care. Thus, psychiatric symptoms should not be viewed as a secondary or additional feature of the movement disorders, but rather, representing important and inherent aspects of these disorders. Although this is true for Parkinson’s disease (PD), it is even more so for several of the atypical parkinsonian disorders, where psychiatric symptoms may represent key features of the clinical syndrome. For instance, in dementia with Lewy bodies, visual hallucinations are among the three cardinal features (1), and in focal lesions of the caudate, neuropsychiatric symptoms occur more commonly than motor disorders (2). Knowledge of the wide variety of psychiatric symptoms and having the diagnostic skills to identify and optimize treatment of these symptoms are thus of major importance in the management of patients with movement disorders. In addition to providing important diagnostic information, they help elucidate the relationship between key brain circuits and psychiatric symptoms.