Introduction
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Despite progress in understanding the neurochemical mechanisms, the exact cause of PD remains undetermined. The main pathological findings are loss of neurons in the substantia nigra and a profound depletion of dopamine in areas of projection pathways from the substantia nigra as in the striatum. In addition, a protein, α-synuclein, bound to ubiquitin accumulates in damaged neurons and contributes to form Lewy bodies, another hallmark of the disease found in cells of the substantia nigra and other brain areas. Several genetic factors, in particular about 10 gene mutations, have been identified in familial cases of PD, but they are observed mainly in early-onset PD and are infrequently involved in late-onset PD.
The prevalence of PD is ∼1% in subjects aged over 65 years. The median age at diagnosis is 60 years, so less than about 40% of cases begin after age 60 years. Usually late-onset PD is defined by first symptoms occurring after the age of 60 years. Hence very late-onset PD, beginning after the age of 75 years, is not frequently observed. The incidence of PD rises with age until 80 years, but seems to decrease in the ninth decade. The mean duration of the disease from diagnosis to death is 15 years. Therefore, owing to age factors and referral bias, most PD patients seen in geriatric settings have a longstanding PD with impaired independence of other complications.
Risk factors for PD have been extensively studied. The existence of a family history of PD is found in 6–10% of cases. Weak associations have been found between PD and head injuries, rural living, obesity and exposure to herbicides or pesticides. Male gender is a controversial risk factor, depending on the population studied. Cigarette smoking and coffee consumption seem to be protective factors.
Signs and Symptoms of Very Late-Onset Parkinson’s Disease
Many symptoms can be caused by PD or other parkinsonian syndromes. Some of them are motor symptoms such as tremor, difficulties in moving, writing and walking, falls and changes in gait and posture. Others are non-motor symptoms such as bradyphrenia (slowness of mental function), depression, memory problems and dementia, constipation, bladder dysfunction and autonomic dysfunction (gastrointestinal, sexual, cardiovascular). Physical examination shows extrapyramidal signs which can suggest PD to the geriatrician (Table 63.1).
Table 63.1 Cardinal signs of Parkinson’s disease.
| Sign | Characteristics in PD | Conditions other than PD that should be considered |
| Tremor | At rest, 4–6 s−1, asymmetric at the beginning, regular, increased by emotion, decreased by posture | Postural tremor: essential tremor, hyperthyroidism, drug-induced tremor, exaggerated physiological tremor, dystonia tremor Intentional tremor: cerebellar disorders |
| Bradykinesia and akinesia | Slowness and/or poverty of movements and speech, loss of facial expressions | Depression, dementia, hypothyroidism, drug-induced (sedatives), encephalopathy, parkinsonism other than PD |
| Rigidity | Found on passive movements, asymmetric at the beginning, lead-pipe type at examination | Pyramidal rigidity: abnormalities of reflexes and other neurological signs Oppositional rigidity: not permanent Extrapyramidal rigidity other than PD: axial or symmetrical at the beginning |
PD usually starts in an insidious manner and progresses slowly. Cardinal extrapyramidal signs do not appear at the same time and tremor can precede bradykinesia and rigidity for several months or years. PD signs are usually asymmetric or even unilateral at the beginning and become bilateral and/or symmetrical as the disease progresses.
Other signs are frequent in PD, especially as the disease progresses. Abnormal posture with flexion of limbs and trunk is observed when standing, and walking shows a decrease in step length and height and reduced swing of the arms. Neuropsychiatric symptoms are dominated by anxiety and depressive syndrome. Anxiety disorders encountered in PD are mainly generalized anxiety disorder and obsessive–compulsive disorder. Major depression episodes are frequent in PD and about 50% of patients might be affected during the course of the disease. The diagnosis of depression is often difficult because symptoms such as fatigue, sleep disorders and lack of interest may be encountered in PD in the absence of overt depression. Cognitive symptoms might be encountered is PD patients, but cognitive impairment (defined by an abnormally low performance in cognitive testing) is never a sign of early PD and is observed in PD only after several years of evolution (PD-related dementia).
Autonomic disorders are dominated by orthostatic hypotension and constipation. Orthostatic hypotension, frequently found in PD, is directly related to autonomic dysfunction and is often worsened by antiparkinsonian drugs. Orthostatic hypotension is often asymptomatic but can cause discomfort or fainting syncope. Orthostatic hypotension is defined by a decrease in systolic blood pressure by 20 mmHg (or diastolic BP by 10 mmHg) within 3 min following the passage from supine to standing. Repeated search of orthostatic hypotension is a part of the monitoring of any parkinsonism patient. Constipation is found in about 50% of PD patients and is related to bowel motility impairment, sphincter dysfunction and poor physical activity. Autonomic symptoms also include sweating, drooping, sexual dysfunction and urinary symptoms, such as urinary frequency, urgency and dysuria, whose links with PD can be established after having rejected the role of urinary infection, bladder or prostate diseases and/or anticholinergic drugs.
Differential Diagnosis of Parkinson’s Disease
Tremor
PD may begin with isolated tremor. Other causes of tremor are listed in Table 63.1. Intention tremor which is increased by voluntary movement orients towards cerebellar diseases, and also other components of cerebellar syndrome (dysmetria, hypotonia, dysdiadokinesia, dysarthria) if present.
Postural tremor is increased by maintaining posture. Hyperthyroidism is easily recognized by other signs and blood determination of thyroid-stimulating hormone (TSH). Essential tremor is the main differential diagnosis. Family history of tremor and involvement of the head and voice are very suggestive of essential tremor. In difficult cases, brain single-photon emission computed tomography (SPECT) using a transporter of dopamine, ioflupane (DaTSCAN), shows a normal pattern in essential tremor and abnormalities in PD and other parkinsonian syndromes (except neuroleptic-induced parkinsonism). Drugs that might induce tremor include amiodarone, lithium, bronchodilators, metoclopropamide, neuroleptics, valproate and theophylline.
Extrapyramidal Syndromes Other Than Parkinson’s Disease
Extrapyramidal syndromes can be observed in several conditions other than idiopathic PD. Especially in very late-onset parkinsonism, the relative frequency of extrapyramidal syndromes other than PD is greater than in early-onset parkinsonism, accounting for 20–40% of new parkinsonism cases in the elderly. The main causes of extrapyramidal syndrome are given in Table 63.2. In most cases, medical history and physical examination allow their identification. Parkinsonian syndrome other than PD responds poorly to L-dopa. This can be recognized by medical history if the patient was given L-dopa. In difficult cases, the response to L-dopa can also be clinically assessed (Box 63.1).
Table 63.2 Causes of extrapyramidal syndrome other than Parkinson’s disease.
| Causes of extrapyramidal syndrome | Characteristics |
| Frequently observed as very late-onset parkinsonism | |
| Drug-induced parkinsonism | Exposure to neuroleptics (or other drugs) before the onset of parkinsonism. Dyskinesia is frequent. No tremor. Ioflurane SPECT normal pattern |
| Lewy body dementia | Dementia occurring a few months before or after the onset of parkinsonism, hallucinations, severe adverse reactions to neuroleptics |
| Alzheimer’s disease | Parkinsonism is infrequent in Alzheimer’s disease and is observed at moderate or severe stages. Hippocampal atrophy on MRI. Ioflurane SPECT normal pattern |
| Progressive supranuclear palsy | Postural instability and repeated falls occurring early in the course of the disease, axial rigidity, limitation of vertical gaze, neck dystonia, impaired saccades on ocular electrophysiology. No tremor. MRI: midbrain atrophy |
| Cerebrovascular disease | Parkinsonism associated with several cerebral infarctions on MRI and worsening of parkinsonism signs after infarctions. Usually with multilacunar state, pseudobulbar syndrome, emotional lability, pyramidal signs and/or vascular dementia |
| Normal pressure hydrocephalus | |
