The most common dementias associated with movement disorders in old age are dementia with Lewy bodies (DLB), Parkinson’s Disease (PD) dementia (PDD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). These different conditions can be grouped according to their characteristic neuropathological characteristics as synucleinopathies (DLB and PDD) or tauopathies (CBD and PSP). Clinical neuropsychological test findings by themselves are not diagnostic and it is often hard to between the features of PDD and DLB, even if subtle differences occasionally emerge. CBD and PSPS have also symptom overlap and it is also difficult to distinguish these two. However, neuropsychological evaluation that weighs test results, interview formation about disease course, neuroimaging findings, comorbidities and motor and non-motor symptoms can help ruling out or supporting a specific diagnosis. When a patient with a movement disorder and dementia is referred for neuropsychological evaluation, the issue is often one of facilitating differential diagnosis and determining if other factors (medication, depression) are producing cognitive compromise. Other issues are patient selection for treatment, characterization of deficits to determine interventions and documenting deficit progression.

Epidemiology

There is not much agreement among scholars about the prevalence of Parkinson’s Disease or Parkinson’s Disease dementia. It all depends on the diagnostic criteria, sampling and methods used. The writers of this text say that dementia incidence is about 3% for persons with PD younger than 60 years and 15% for persons with PD older than 80 years. Low education and advancing age have been associated with increased dementia risk in PD, but there are also some other factors. DLB is said to be the second most common cause of dementia and it counts up to 20% of the cases coming to autopsy. According to a review of six different studies, the prevalence of DLB ranges from 0 to 5% among the general population and from 0 to 31% among dementia cases.

The incidence and prevalence of CBD have not been widely studied. Many studies show different prevalence rates. Dementia and neurobehavioral abnormalities were thought to be rare CBD, but now they are accepted to be a common problem in this disease. One study mentioned that only 19% of 36 patients had slight generalized cognitive impairment, but another study stated that among 13 pathologically confirmed cases, 69% had dementia at presentation. H1/H1/ tau haplotype is identified as heightening susceptibility to CBD and PSP, but no clear genetic etiology has been identified. The population prevalence of PSP ranges from 3 to 6 per 100000 and a recent Russian study states that the annual incidence of PSP is estimated at 5 per 100000 in persons older than 50 years. Incidence and prevalence of PSP is not strongly associated with genetic or demographic risk factors, except older age. A recent study observed dementia in 57% of people with PSP.

Clinical and neurological presentation

There have been some separate criteria proposed for PDD and DLB. An important feature differentiating DLB and PDD is the time of onset of dementia in relation to onset of motor signs. A diagnosis of DLB is made, when neurobehavioral symptoms precede or occur within the first 12 months of the motor signs. A diagnosis of PDD is made, when cognitive symptoms have their onset more than 12 months after the onset of parkinsonism. Logically, Parkinson’s disease dementia requires that a prior diagnosis of Parkinson’s disease has been made. The criteria for PD diagnosis are the presence of a parkinsonian syndrome. This is evidenced by bradykinesia (slow movement), muscular rigidity, resting tremor, postural instability, visual, vestibular or cerebral dysfunction. Also, for the diagnosis of definite PD, at least three supportive features are required: progression of symptoms, unilateral onset, persistence of symptom asymmetry, excellent response to levodopa, levodopa response sustained for 5 years, dyskinesia or a clinical course over 10 years. PD becomes most often symptomatic during the sixth decade of life, but young onset can occur. The most common initial cognitive complaint in PDD and DLB patients involve memory complaints. 67% of PDD and 94% of DLB patients initially complained of memory problems. Patients also may initially complain about word-finding problems, keeping up with conversation due to slowness of thought, financial management, problems with concentration and apathy. People with PDD have problems with day-to-day repair tasks with which they were previously facile. DLB patients also complain of hallucinations, visual distortion and sleep behaviour disorder

Pathological confirmed CBD can have heterogeneous clinical presentations. Corticobasal syndrome (CBS) is characterized by the core motor and cortical features of CBD regardless of etiology. The term CBD is reserved for neuropathologically distinct CBD regardless of clinical presentation. CBD onset is often in the sixth decade of life and after the diagnosis, the mean time to death is about 7 years. CBD can present with either motor or cognitive dysfunction. Initial complaints include stiffness, clumsiness or jerkiness or an arm and sometimes clumsiness of a leg. The motor features of CBD include asymmetric, progressive, akinetic-rigid parkinsonism of gradual onset, minimal response to levodopa, hand, limb and speech apraxia (movement). Cortical signs in CBD are cortical sensory deficits, alien hand syndrome and ideomotor apraxia. Alien hand syndrome is the feeling that your limb(s) is/are not your own and that they move involuntary.

PSP has some of the same features as CBD and frontotemporal dementia. Signs of PSP may be evident as early as age 40, while formal diagnosis typically occurs after age 60 and there are very high incidence rates after age 80. There are no effective pharmacological or neurosurgical treatments available for patients with PSP and after diagnosis, the patients survive 5 to 10 years after diagnosis. The criteria of possible PSP require a gradually progressive disorder beginning at age 40 or later, postural instability in the first year of disease, vertical supranuclear gaze palsy and other diseases that could explain these features need to be excluded. Probable PSP requires postural instability, vertical supranuclear gaze palsy, and falls in the first year of onset. The earliest symptoms of PSP are imbalance, like falls, worsened postural reflexes and dysarthria (motor speech problems). There is a poor hand-eye coordination, and because of this, an early symptom of PSP is sloppy eating. Symmetric bradykinesia is also common. Also, there is a slowing of thought and gaze. There are no universally accepted clinical subtypes or categories of PSP. All but 15% of the cases could fall in the traditional PSP syndrome, and the rest falls in PSP associated with PD-like symptoms.

Neuropathology

PD has been defined by neuronal loss and Lewy bodies (LB) in the substantia nigra. But these patients also have a presence of LB and Lewy neurites (LN) outside the substantia nigra. One study found three phenotypes of PD patients: a group with early, prominent dementia and akinetic-rigid PD (this corresponds clinically to DLB), a group of older PD patients (onset after 70 years) developing dementia in 3-10 years (corresponds to PDD) and a younger PD group (onset before 70 years) in which dementia occurs late in the disease (after 10-15 years). Many people with DLB have amyloid plaques at autopsy, while in PDD this is less. Both PDD and DLB involve dysfunction of the dopaminergic and cholinergic systems. The pathological features of CBD include ballooned neurons, which are mostly found in frontoparietal cortex, but they are also found in the amygdala, insular cortex and anterior cingulate. The frontal and frontoparietal cortices show asymmetric atrophy. There are also tau-containing neuronal inclusions in the cortex. The substantia nigra shows cell loss and there is neuronal loss in many systems. In PSP, the whole substantia nigra is compromised and there is a dopaminergic depletion in the caudate and putamen. There are also neurofibrillary tangles in the brain stem and basal ganglia.

Neuroimaging findings

For patients with PDD, studies have shown an association between dementia and medial temporal, neocortical and amygdala atrophy. Studies show also greater parietal, temporal and occipital neocortical atrophy in DLB than PDD. Some studies show there is a greater PIB uptake (beta-amyloid deposition, chapter about Alzheimer) in DLB, but not PDD. Studies also show that posterior cerebral blood flow and glucose metabolism is especially reduced in DLB and PDD. In patients with CBD, MRI reveals cortical atrophy, especially frontoparietal. Other findings show dopaminergic abnormalities in CBD. MRI findings of PSP patients show midbrain atrophy. Cortical atrophy also occurs and frontal atrophy is linked with executive dysfunction.

Neuropsychology

Performance on simple attention tasks is usually preserved in PD, but as the disease progresses, impairments can even be found on cued attention tasks. Early on in PD, there are impairments in working memory tasks and these deficits progress in PDD. Complex attention tasks (like the Stroop task) are more likely than simple tasks to elicit attention impairment in PDD and DLB. Planning is often slowed or inaccurate in PD, these patients are also found to be slow in conceptualization and they have difficulty to switch between two different sets of stimuli. People with PDD have more impaired verbal fluency than PD patients, but verbal fluency is similarly impaired in DLB and PDD. Visual confrontation naming is preserved in PD. There is a retrieval deficit in PD. Recognition is also not necessarily intact in PD. Semantic encoding might also be deficient in PD. DLB and PDD show similar memory impairments. However, DLB shows poorer recall and more rapid rates of forgetting, PDD makes more perseverative errors during list learning. There are comparably severe deficits in PDD and DLB that have been observed on different visuospatial and constructional tasks. These visuospatial and constructional tasks deficits are even found in mild DLB. They show deficits in copying of figures (you can see a picture of this on page 342 of the Neuropsychology book).

Depression is often undertreated in PD. Anxiety and depression often go unrecognized by clinicians treating PD. It is therefore important to screen for neuropsychiatric conditions. Depression is common in PD and it occurs in about half all patients. Depression prevalence estimates for PDD and DLB are not really available. One study found that major depression occurs in about 13% of patients with PDD and in about 19% of patients with DLB. About half the patients with PD have symptoms of anxiety, and 75% of those patients with PD and depression may have a comorbid anxiety disorder. However, the prevalence of actual anxiety disorders in PD ranges from 5% to 40%. Almost 20% of PD patients had generalized anxiety and 20% had a social phobia. A considerable number of PD patients have obsessive compulsive disorder. Anxiety occurs in two-thirds of patients with DLB. Psychosis is common in PDD and DLB, but more common in PD. Hallucinations occur in 76% of DLB and 54% of PDD and delusions occur in 57% of DLB and 29% of PDD. They are of similar quality in both patient groups.

Patients with CBD have marked impairments working memory (digit span backward). Patients with CBD have also executive dysfunction. The aphasia in CBD is most commonly non-fluent. The language problems in CBD is phonologic. Verbal fluency is impaired, because of executive demands on those tasks. Semantic memory tasks like conceptual matching and expressive vocabulary is relatively preserved. Apraxia is often ideomotor, patients most often have difficulty demonstrate the use of tools. Memory impairments in CBD are encoding and retrieval deficits, but they are milder and rarer than the apraxia and impairments in executive functions. Visuospatial impairments have also been observed in CBD, as well as drawing deficits. 73% of CBD patients have depression, and apathy (40%), irritability (20%) and agitation (20%) also occur.

In PSP patients, verbal attention is often normal, but deficits in visual attention are common. Executive dysfunction occurs early in PSP and it stems from deficits of the basal ganglia and prefrontal cortex. People with CBD show compromised planning, cognitive flexibility and problem solving. The progression of these deficits is especially rapid in PSP patients, compared to the other patients. Speech problems also occur earlier and are more common in PSP than in other movement disorder groups. Verbal fluency is impaired and letter fluency is more affected than category fluency. There are episodic memory deficits present in PSP, but these are less severe than the deficits in PDD and DLB. Free recall is impaired, but recognition discrimination is relatively normal. Remote memory is not really affected. PSPS patients show oculomotor deficits; the voluntary vertical eye movements are deficit. They show a reduced blinking frequency. Apathy is the most common neuropsychiatric symptom in patients with PSP and the prevalence may be as high as 90%. It is far more common and severe in PSP than PD. People with PSP also show behavioural signs of disinhibition. They may also show a change in personality, including increased irritability.

Neuropsychological assessment

For the assessment of these movement disorders, medical records should be reviewed. This is especially the case for the disorders presenting with dementias. Next to the usual information gleaned from medical records, reviews for patients with movement disorders should also address other things. They should assess age and age at onset of movement disorder symptoms, the age at onset of cognitive changes, the side of onset of movement disorder symptoms (DBL and PSP are more symmetric, while PD and CBD are asymmetric), the nature of parkinsonian symptoms, presence of motor fluctuations, the existence of pathological daytime sleeping, presence of visual problems and tremors that might interfere with test administration, the presence of attention fluctuations and hallucinations, comorbid medical conditions, utilization of certain medications that might impact concentration or memory and history of prior neurosurgical intervention for movement disorder

Interview

The information that is obtained from medical record review, should be verified during interview. It should also be established whether there is a family history of dementias or movement disorders. During interviews, the question arises whether patients and care givers are accurate in reporting cognitive, behavioural and functional changes. Research has found that patients are accurate reporters of disability, even when there is cognitive compromise or depression. The discrepancies between patient reports and care partner reports increase as a function of patient cognitive impairment and depression. Patients frequently complain of memory disorders initially, but what they describe as memory disorders may actually represent other deficits. For example, the inability to recall how to operate equipment may refer to executive dysfunction. It is important to prepare the patient for evaluation during the interview. The interviewer needs to make the patient as less anxious as possible. Patients should be encouraged to report what they feel. Patients should also be monitored for fatigue and also whether they’re alert or not (especially patients with DLB).

Screening instruments

Neuropsychologists need to screen for cognitive impairment in persons with movement disorders. The use of screening instruments has been the subject of empirical investigation in PD and PDD, but has received less attention in PSP, CBD and DLB. It is important to know how well screening instruments perform in detecting cognitive impairments in movement disorders. The advantages of cognitive screening instruments include the simple administration and scoring, the brevity, patient acceptability and limited expense. Another issue is that there are few screening instruments that have been developed for movement disorders. Recently, more emphasis has been placed on developing instruments for the use of PD and PDD, but no instruments have been developed specifically for PSP, CBD and DLB. Two widely used screening instruments not specifically designed for PDD and DLB are the Mini-Mental State Exam (MMSE) and the Dementia Rating Scale (DRS). However, the MMSE de-emphasizes working memory and executive functions and lacks sensitivity to cognitive changes associated with subcortical-frontal dysfunction. The DRS’s sensitivity in detecting cognitive impairment in PD has not been adequately addressed. Some subtests of the DRS are more helpful in distinguishing PD patients from healthy controls than others.

Test selection should consider the patient’s condition or the differential diagnosis, the patient and caregiver concerns, the referral questions, the properties of the test and the patient’s ability to tolerate and cooperate with the test. When researchers evaluate patients with movement disorders, awareness of the impact of various features of movement disorders, like sleep disturbance, apraxia and motor fluctuations, on test performance need to be considered. Standard test administration methods may have to be modified when working with these patients. People with PSP have downward gaze palsy, and this makes it difficult for them to voluntarily look down at test forms. Patients with speech impairments may want to point rather than giving oral responses. Patients with tremors or apraxia may require help from the examiner when completing tests or questionnaires that require writing or circling alternatives. These scales might be administered verbally. It is also recommended to test patients when they are on antiparkinsonian medication. Another issue in PDD and PD is that symptoms of depression and anxiety may overlap with those of the movement disorder. Sleep disturbance, lack of energy, psychomotor retardation, sexual dysfunction and masked facial expressions can be observed in PDD, DLB, PSP and depression. Some scientists have suggested not to look at morning awakening and psychomotor slowing when diagnosing depression in PD. Rating scales might overestimate depression.