Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Movement disorders in older adults can be broadly classified into the akinetic-rigid hypokinetic conditions, in which voluntary movement is reduced, and hyperkinetic conditions, in which excess involuntary movements called dyskinesias are present ( Box 64-1 ). Dyskinesias can be further classified into tremor, dystonia, tics, myoclonus, and chorea. This distinction is as not absolute as, for example, in Parkinson disease (PD), the most common akinetic-rigid syndrome, involuntary movements are often present. Akinetic-rigid syndromes are usually associated with poor mobility and difficulty with walking because of the presence of a gait apraxia.
Movement disorders are common in older age and are a significant cause of impairment, disability, and handicap. Once diagnosed, these disorders can often be effectively treated. These conditions often present in older people at an advanced stage, and it is not uncommon in older patients acutely admitted into the hospital for other conditions to make the diagnoses of hitherto unrecognized essential tremor, parkinsonism, orofacial dyskinesia, or drug-induced movement disorder.
The akinetic-rigid syndromes are a group of disorders characterized by parkinsonism, which results from the combination of akinesia, rigidity, and, often but not always, tremor ( Box 64-2 ). Parkinsonism is often associated with impaired balance and a gait apraxia leading to falls and impaired mobility. Levodopa-responsive parkinsonism of unknown cause that has particular clinical features, a characteristic clinical progression, and Lewy body neuropathology in the substantia nigra is called idiopathic parkinsonism or PD and accounts for approximately 70% of cases of parkinsonism. Other causes of parkinsonism include drugs, vascular disease, and, much less frequently, multisystem degenerative conditions, which include progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. With increasing age, not only does the risk of parkinsonism increase but also the likelihood of parkinsonism having a cause other than PD.
Parkinson disease (idiopathic/sporadic parkinsonism)
Drug-induced parkinsonism
Neuroleptic drugs
Calcium blocker cinnarizine
Vascular parkinsonism (pseudoparkinsonism)
Multi-infarct states
Single basal ganglia/thalamic infarct
Binswanger disease
Multisystem degenerative diseases
Progressive supranuclear palsy
Multiple system atrophy (striatonigral type)
Corticobasal degeneration
Alzheimer disease
Wilson disease (young-onset parkinsonism)
Dementia with Lewy bodies
Neurofibrillary tangle parkinsonism
Toxins
MPTP
Manganese
Familial parkinsonism
Postinfectious parkinsonism
Creutzfeldt-Jakob disease
AIDS
Postencephalitis (encephalitis lethargica)
Miscellaneous causes
Hydrocephalus
Posttraumatic
Tumors
Metabolic causes (postanoxic)
AIDS, Acquired immunodeficiency syndrome; MPTP, 1-methyl-4-phenyl-1,2,2,6-tetrahydropyridine.
Although PD can present at any age, it rarely occurs outside of old age. Cross-sectional prevalence studies of PD and parkinsonism show at least two thirds of subjects to be older than 70 years. PD is usually insidious in onset and may have a long symptomatic phase before eventual diagnosis, with symptoms being mistakenly attributed by patients and their physicians to the inevitability of “old age.” The rate of progression in PD is strongly related to age at onset rather than to disease duration, which explains the often rapidly disabling motor deterioration associated with dementia seen in subjects with onset beginning after 70 years of age (late-onset disease). Minimal signs of parkinsonism may result from normal aging changes in the basal ganglia or incidental Lewy body changes, making the diagnosis of PD in older people even more difficult.
Classically PD has been considered a disorder of voluntary motor control, which in young subjects is a reasonable assumption. However, the increasing realization of the widespread nature of neuropathology in PD, coupled with our increasing recognition of nonmotor symptoms, has now led to the concept of PD being a multisystem multiorgan disorder. Nonmotor symptoms are increasingly common with disease progression and older age at disease onset and therefore are a major feature of PD in older subjects. Cognitive impairment, often progressing to dementia, is the most powerful factor that determines quality of life in older people with PD. Late-onset PD is probably best thought of as being primarily a dementia associated with poor mobility and a high risk of falls.
PD is characterized by cell loss and gliosis in the substantia nigra and other pigmented brainstem nuclei that are often visible to the naked eye on sectioning the midbrain. Aging also results in cell loss in the substantia nigra, although the distribution of cell loss is very different from that seen as a result of PD. Surviving cells in the substantia nigra contain typical inclusions in the cytoplasm called Lewy bodies, which are now known to be largely an aggregation of a protein called α-synuclein. Most cases of PD diagnosed in life are found to have Lewy bodies in the substantia nigra. However, Lewy body pathology in the substantia nigra does not necessarily lead to the clinical picture of PD, and conversely, largely from the studies of familial parkinsonism, other pathologies not involving Lewy bodies can give rise to a clinical picture typical of PD. Lewy bodies are also found in other specific brain sites outside the brainstem, including the cerebral cortex, olfactory bulb, and enteric plexi. Lewy bodies can be found in up to 10% of postmortem examinations in older subjects with no apparent history of parkinsonism in life (incidental Lewy body disease). It is unclear whether such individuals, if they had survived, would have developed PD or, because of protective mechanisms, were able to contain the disease process in a subclinical state. The role of the Lewy body in the pathology of PD is still unknown, and it is unclear whether the Lewy body represents a defense mechanism or the result of the primary disease process.
PD also involves the ascending serotonergic, noradrenergic, and cholinergic projections to the cortex and basal ganglia. Clinicopathologic studies have demonstrated that coexisting neuropathology within the striatum and in other areas of the brain is extremely common in older subjects with histologically confirmed PD. Braak and colleagues have proposed that the primary degenerative process in PD, based on the assumption that the presence of Lewy bodies indicates neuronal loss, begins not in the substantia nigra but in the olfactory tracts, lower brainstem, and enteric nervous tissue. This model fits well with the increasing recognition that rapid eye movement (REM) sleep disorders, hyposmia, and constipation may precede the motor symptoms of PD by several years. The proposed pattern of disease progression also indicates the potential for interaction with environmental agents via the olfactory system and gut.
Akinesia is the central motor abnormality in PD that refers to a lack of spontaneous voluntary movement, slowness of movement (bradykinesia), and faulty execution of movement. Marsden brilliantly described akinesia as the “failure to execute automatic learned motor plans.” Voluntary movements tend to be of low amplitude and to show increased fatigability. There is a particular difficulty with sequential and concurrent self-paced movements. When asked to oppose the index finger to the thumb in a tapping motion, patients often start with reasonably fast, large-amplitude movements, but the speed and amplitude then rapidly decrease and the movement fades away. Akinesia in the lower limb is best tested by asking the patient to tap the heel of the foot on the floor as rapidly as possible; in this situation, akinesia can be heard as well as seen. Older patients often find bedside tests for akinesia difficult to execute and may perform poorly because of cognitive impairment, painful arthritis, restricted joint range, and muscle weakness. Action tremor from any cause can interfere with the quality of normal hand and finger movements, and this can make the assessment of akinesia difficult in the presence of essential or dystonic tremor.
Rigidity is an increased resistance of muscle to passive stretch felt by the examiner. Clinically, rigidity is best detected at the wrist joint. The patient is asked to relax as fully as possible while the examiner makes flexion and extension movements of the wrist joint with the patient's forearm supported. Passive movements of the head can be used to detect axial rigidity. Parkinsonian rigidity is not velocity-dependent and is present to the same degree at all joint positions in flexion and extension (“lead-pipe” rigidity). Activation procedures, akin to the Jendrassik maneuver to enhance tendon jerks, can bring out “activated rigidity” that was not previously present. Transient activated rigidity may be a normal finding in anxious individuals. Activated rigidity in the neck muscles may be the first sign of rigidity in PD. Tremor in the upper limb due to any cause will result in a ratchet-like quality of intermittent resistance at the wrist joint called cogwheel rigidity that is not specific to PD.
Tremor, usually of the hand, is the presenting feature of PD in approximately 70% of cases. Hand tremor characteristically occurs at rest when the postural muscles are relaxed and has a frequency of approximately 4 to 6 Hz. In an anxious patient, postural tremor can easily be misidentified as a resting tremor. Most patients with PD manifest a range of resting, postural, and action tremors. A resting tremor of the hand involving the thumb and index finger described as “pill-rolling” and often brought out when the patient is observed walking is very suggestive of PD or drug-induced parkinsonism. Tremor usually begins insidiously in one hand before spreading to the leg on the same side. After a further delay of sometimes a year or more, the opposite hand and leg become affected. In rare cases, PD can present with tremor alone (tremor-dominant PD) with variable degrees of mild rigidity and akinesia found on examination. Tremor-dominant PD is a slowly progressive disorder and can be very difficult to distinguish from essential and dystonic tremors. Individuals with a diagnosis of PD recruited into trials of neuroprotection in PD, who are subsequently found to have no evidence of nigrostriatal dysfunction on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scans, may well have dystonic tremor.
Postural balance can be assessed clinically by asking the patient to stand and then gently pushing the patient forward from behind, with the other hand in front to prevent a fall. Falls or feelings of imbalance strongly suggest the presence of impaired righting reflexes, even if this is not evident at the time of examination. Axial motor disturbances leading to gait disturbance, dysphagia, and dysarthria are a feature of late-onset PD and often respond poorly to drug treatment.
In older people with PD, the severity of clinically elicited motor signs, the benchmark of disease severity in clinical research trials, is often poorly correlated with functional impairment and handicap in daily living. For example, despite the bedside demonstration of severe akinesia in the clinic, one patient still managed to make breakfast that day, albeit slowly, and was able to make the arduous journey to the hospital.
Nonmotor symptoms, particularly hyposmia, sleep disorder, and constipation, may predate the onset of motor symptoms by many years. Nonmotor features of PD are varied and, with disease progression, dominate the clinical picture. In late-onset PD, nonmotor features are usually advanced by the time of diagnosis and progress more rapidly than in earlier-onset disease. Autonomic system involvement leads to postural hypotension, urinary incontinence, sexual dysfunction, constipation, and abnormalities of sweating. The progression of PD pathology in the cerebral cortex leads to a range of neuropsychiatric and cognitive problems, including dementia, psychosis, hallucinations, apathy, and depression. Sensory symptoms, usually painful in nature and involving the lower limbs, also occur and are difficult to treat successfully. A rating scale for nonmotor symptoms has been developed, but, like so many assessment scales, it is more useful in research settings than in clinical practice.
Dementia and cognitive impairment are common problems in the management of PD in older adults. The cause most frequently appears to be Lewy body pathology in the cerebral cortex. Dementia that develops a year or more after parkinsonism is described as PD dementia (PDD), whereas dementia present at the start of the illness is called dementia with Lewy bodies (DLB). These two conditions are generally thought to represent two ends of a spectrum of Lewy body disease. The situation is more complicated than this with the expansion in the United Kingdom of organized memory clinic care for people with dementia. This has resulted in the identification of individuals with established dementia, who never fulfilled DLB diagnostic criteria, who subsequently develop typical features of PD, and who appear to benefit from cautious levodopa treatment. The risk of dementia in older adults with PD is five times that of age-matched subjects without PD, and after 8 years of follow-up the prevalence of dementia may reach nearly 80%.
Dysthymia, or mild depression, is fairly common in PD, but major depression is unusual in the absence of previous significant depressive illness. The natural history of depression or depressive symptoms in PD and the response to antidepressant drug treatment has been poorly studied. Apathy is also frequently described in individuals with PD and may be mistaken for depression. A range of nocturnal and daytime sleep disorders is now well described in PD and include REM sleep behavior disorder and excessive daytime sleepiness.
Visual hallucinations are common in PD and occur early in late-onset disease. Rather than simply being side effects of antiparkinsonian medication, visual hallucinations are now thought to be the direct result of Lewy body pathology in the ventral-temporal brain areas, indicating that the second half of the course of the disease has been reached. Visual hallucinations have been suggested as a useful marker to distinguish PD from non–Lewy body parkinsonism.
Psychosis in PD usually occurs in older patients with established cognitive impairment or dementia and again indicates the presence of significant cortical disease.
Delirium in PD is also common in older patients with cognitive impairment and is precipitated by the usual suspects commonly invoked in geriatric practice. All antiparkinsonian medications increase the risk of delirium; this risk is greatest with anticholinergics, dopamine agonists, selegiline, and amantadine. Visual hallucinations commonly occur in conjunction with psychosis or delirium. Delirium has a remarkable but unexplained and little researched effect on motor symptoms in PD. Patients with acute delirium are often hyperactive and wander around the ward despite refusing all antiparkinsonian medication for days at a time. As the delirium lifts and medication is reintroduced, motor function again deteriorates to the previous parkinsonian state of frozen immobility.
The diagnosis of PD is a two-stage process that remains heavily dependent on clinical skills. First, the symptoms of parkinsonism need to be sought in the history and the signs of parkinsonism established by clinical examination. Progressively small handwriting (micrographia) with the written word disappearing into a shaky line is strongly suggestive of parkinsonism. Difficulty turning over in bed is also a good clue to the early development of axial akinesia. A good witness account, usually from a spouse, is very useful in confirming the often rather general and nonspecific slowing down seen in older patients with PD. The gradual inability to keep up with a spouse on daily routine walks is again a useful early indication of gait disturbance and akinesia. Loss of saliva from the mouth at night (sialorrhea) is also helpful, indicating the presence of akinetic bulbar function. Second, if parkinsonism is detected, consideration has to be given to what type of parkinsonism is present by applying validated clinical diagnostic criteria ( Box 64-3 ).
A progressive usually nonfamilial disorder with bradykinesia (slowness of initiation of voluntary movement, progressive reduction in speed and amplitude of repetitive movement, and difficulty switching smoothly from one motor program to the next) and at least one of the following:
Muscular rigidity
Coarse 4 to 6 Hz resting tremor
Impaired righting reflexes (not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction)
Absolute exclusion criteria are the following:
Exposure to neuroleptic drugs within the year before the onset of symptoms or exposure to MPTP
Presence of cerebellar or corticospinal tract signs
Past history of encephalitis lethargica or viral encephalitis with oculogyric crises
Stepwise progression or a history of multiple strokes
Presence of communicating hydrocephalus or a supratentorial tumor
Presence of severe early autonomic failure
Supranuclear gaze palsy
MPTP, 1-Methyl-4-phenyl-1,2,2,6-tetrahydropyridine.
In older patients, the diagnosis of parkinsonism can be extremely difficult, even in expert hands, particularly when the clinical picture is complicated by other diseases, cognitive impairment, depression, and atypical features. The diagnosis of parkinsonism in acutely ill frail patients in the hospital should be approached with particular caution because, once the patient has recovered from the acute illness, the apparent signs of parkinsonism may not be present. A confident diagnosis of parkinsonism cannot always be made in older people, and sometimes a trial of levodopa at an adequate dosage (at least 600 mg daily) may be required. The use of DaTSCAN-SPECT imaging of the nigrostriatal tract using a radiolabeled tracer for the dopamine transporter may help distinguish atypical postural and action tremors in older patients and lead to the correct diagnosis of PD, essential tremor, and dystonic tremor.
How good are experts at distinguishing PD from other types of parkinsonism? Two important clinicopathologic brain bank studies addressed this problem and demonstrated that diagnostic accuracy for PD at death, when diagnostic accuracy is going to be highest, was only approximately 76%. Diagnostic accuracy in later cases referred to a brain bank was shown to have improved to approximately 84%. The use of stringent clinical diagnostic criteria can improve the specificity for correct diagnosis to over 90% but at the expense of a reduced sensitivity of approximately 70% since true but clinically atypical cases are excluded.
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here