12 I ACNR • VOLUME 6 NUMBER 5 • NOVEMBER/DECEMBER 2006 Cognitive Profiles of Parkinsonian Syndromes What the MMSE won’t tell you and why In the early 1970’s a group of psychiatrists devised the Mini Mental State Examination (MMSE) 1 “for the serial testing of the cognitive mental state in patients on a neu- rogeriatric ward”. The original sample of 69 patients included, apart from patients with affective illness, schiz- ophrenia and neurosis, 29 patients with “dementia syn- dromes due to a variety of brain diseases”, reflecting the concept of dementia as “a global deterioration of intel- lect”. Thanks mainly to its brevity MMSE became the most widely used cognitive screening test, applied to a variety of neurological conditions for which it was not originally designed, among them Parkinson’s Disease (PD) and related disorders. There are two serious problems connected with the use of MMSE in this patient group. Firstly, MMSE has been demonstrated to be particularly insensitive to frontal- executive dysfunction, which, as will be shown below, constitutes the most common cognitive deficit in basal ganglia diseases. Secondly, based on the unitary concept of dementia, it does not examine different cognitive domains but confines itself to one global ‘dementia score’. It is, therefore, unable to determine qualitative differences between diseases. Seen in historical perspective, these shortcomings of the MMSE are not surprising: frontal dysfunction and selective cognitive deficits in different types of dementia became the focus of scientific research many years after its publication. A test designed at the time in which the routine imaging procedure was pneu- moencephalography can hardly be expected to be state- of-the-art 30 years later. This does not mean, however, that cognitive assessment has to be long and laborious. The aim of this review is to demonstrate that brief and simple tests, which can be eas- ily performed at the bedside, can distinguish the cognitive profiles of the individual diseases and detect deficits that would go unnoticed by the MMSE. Motor and cognitive features of parkinsonian syndromes: two sides of the same coin? Although a large number of diseases can present with ‘parkinsonian features’, such as tremor, rigidity or bradyki- nesia, we confine ourselves in this review to five diagnostic entities: PD, Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD) and Dementia with Lewy Bodies (DLB). PSP, CBD and MSA (and to a much lesser degree DLB) share some common features which distinguish them from the classical PD and lead to their designation as Atypical Parkinsonian Syndromes (APS). 2 The borderline between PD and DLB is somewhat arbitrary: according to the current diagnostic criteria a patient presenting with parkinsonism followed by dementia is diagnosed as PD, if dementia precedes the parkinsonism the diagnosis is DLB. 3 While all five diseases are associated with typical (or even pathognomonic) features (Table 1), none of them can be diagnosed on the basis of one single symptom. This applies in the same degree to motor as to the cogni- tive symptoms. Prominent tremor, for instance, is most often encountered in PD, apraxia in CBD, but both can also occur, albeit usually less pronounced, in other condi- tions, such as PSP. Interpreted in this way, the cognitive symptoms can be as useful in diagnosing the disease as their motor counterparts. In fact, with growing under- standing of fronto-striatal connections it seems likely that at least some cognitive and motor symptoms are different manifestations of the same underlying pathology. 4 The spectrum of cognitive symptoms in parkinsonian syndromes In 1974, around the time of the publication of MMSE, Albert et al 5 described characteristic cognitive and behav- ioural changes in 5 PSP patients (Table 2). They noted that the symptoms were different from those encountered in Alzheimer’s disease (AD), but similar to those Review Article Dr Thomas Bak is currently a lec- turer in human cognitive neuro- science at the University of Edinburgh and visting researcher at the MRC Cognition and Brain Sciences Unit, Cambridge. In 1996 he initiated a specialist Clinic for Disorders of Movement and Cognition (DMC) at Addenbrooke’s Hospital, Cambridge, which he was in charge of until June 2006. In this time he assessed and followed up over 100 patients with different atypical parkinsonian syndromes, mainly PSP and CBD. In November 2005 Dr Bak visited Dr John Steele (the first describer of PSP) on Guam and studied togeth- er with him the cognitive and behavioural aspects of the ALS/Parkinson/Dementia complex of Guam (lytico-bodig). Correspondence to: Dr Thomas H Bak, Human Cognitive Neuroscience, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ. Tel: 0131 6509861, Email: thomas.bak@ed.ac.uk Figure 1: Cognitive profiles of AD, PSP, CBD, MSA, DLB and on the ACE. Figure 2: Letter and category fluency in AD, PSP, CBD, MSA and DLB. PD asymmetrical parkinsonism, including tremor, good L-Dopa response PSP vertical supranuclear gaze palsy, imbalance with falls backwards MSA dysautonomia, cerebellar dysfunction, imbalance with falls CBD apraxia, alien hand syndrome, cortical sensory dysfunction DLB fluctuating course with periods of disorientation, visual hallucinations Table 1: Typical features of different parkinsonian syndromes: • slowing of thought processes • impaired ability to manipulate knowledge • forgetfulness • behavioural and personality changes Table 2: The key symptoms of the Albert syndrome: Number correct Percentage impaired orientation attention memory verbal fluencies language visiospatial