Neuropsychiatric symptoms and depression in neurodegenerative diseases (2004)

Neurodegenerative disease is a general term for degenerative disorders of the central nervous system, including Alzheimer's disease. In recent years, dementia observed in a group of neurodegenerative diseases, excluding Alzheimer's disease, has been referred to as non-Alzheimer degenerative dementia. Kosaka classified non-Alzheimer degenerative disorders into several different types as shown in Table 1.1 Since many neurodegenerative diseases are characterized by peculiar degenerative forms of neuronal and/or glial systems, they can be classified based on the histopathological characteristics of the affected brain.2Table 2 shows an example of four different types of neurodegenerative diseases classified on the presence or absence of immunological findings obtained by immunostaining of abnormally phosphorylated tau protein, α-synuclein and ubiquitin; (1) neurodegenerative diseases characterized by abnormally phosphorylated tau protein deposits; (2) neurodegenerative diseases positive for both α-synuclein and ubiquitin; (3) neurodegenerative diseases solely positive for ubiquitin; and (4) a group of neurodegenerative diseases that cannot be explained by such protein abnormalities.2 Each neurodegenerative disease exhibits specific neurological symptoms and clinical courses. Furthermore, such neurodegenerative diseases are frequently complicated by mood disorder. Therefore, basic and accurate diagnosis and rehabilitation are essential to the treatment of neurodegenerative diseases. Neurodegenerative diseases with a major lesion in the cerebral cortex (Alzheimer's disease and Pick's disease) are mainly characterized by cerebral focal symptoms represented by aphasia, apraxia and agnosia. Differing from elemental and instrumental aspects of cortical disorders, patients with subcortical disorders frequently develop symptoms associated with consciousness, attention and mood. For example, patients with disorders having subcortical lesions, such as cerebral basal ganglia, frequently develop disturbance of consciousness, decreased attention, and mood disorder. Disturbance of memory is a representative symptom of neurodegenerative diseases. During the initial stage of Alzheimer's disease, disturbance of memory, which is characterized mainly by recent memory, is remarkable. However, subcortical disorders are characterized by impairment of remembrance (oblivion) resulting from decreased attention and concentration, in addition to a delayed process of remembrance. Therefore, the pathological condition of mood disorder is modified by various types of memory disturbance. In general, patients with frontal lobe syndrome exhibit alteration of personality represented by egocentrism, irritability, impulsiveness, decreased interest, regressiveness, childishness, and disinhibition. These symptoms are frequently caused by the disconnection of pathways between the cerebral subcortical nuclei and frontal lobe or by the dysfunction of the communicating system. Even when there is no morphological atrophy of the frontal lobe, functional imaging frequently shows decreased cerebral blood flow and hypometabolism in the frontal lobe in many of these patients. Furthermore, such patients are also characterized by alteration of personality that truly demonstrates hypobulia or abulia, and autistic style in life. Some patients with cortical disorders exhibit aphasia, apraxia, and agnosia. However, even patients with subcortical lesions exhibit amnestic aphasia, agraphia, alexia, or motor dysfunction such as gait apraxia, eye apraxia, and limbkinetic apraxia. Neurodegenerative diseases demonstrating alteration of consciousness include Parkinson's disease, progressive supranuclear palsy, and thalamic degeneration. Phenomena such as free-floating hallucination and ‘periodic substuporous condition’ are frequently observed in progressive supranuclear palsy.3 Unstable cognitive ability caused by alteration of consciousness shows sensory disturbance such as illusion and metamorphosis as a result of perplexity, and these symptoms fluctuate within a short period of time. Each type of neurodegenerative disease is characterized by habitual development of pyramidal, extrapyramidal, and cerebellar symptoms, and these symptoms are useful in establishing a clinical diagnosis. That is, neurological symptoms include tremor, akinesia, and muscular rigidity, as are observed in Parkinson's disease; dystonia in the neck and limbs, and disturbance of ocular movement, as are observed in progressive supranuclear palsy; chorea, as is observed in Huntington's disease; characteristic extrapyramidal symptoms, as are observed in Wilson's disease; and pyramidal symptoms, as are observed in neuro-Behçet's disease and thalamic degeneration. It is important not to overlook minute neurological symptoms. Since the exacerbation or improvement of these symptoms greatly influences the accompanying mood disorder, the improvement of motor function might be the optimal treatment in most cases. Depressive symptoms observed in neurodegenerative diseases do not exhibit prominent characteristics. Patients with neurodegenerative diseases occasionally complain about mental problems such as depressive mood, a sense of sorrow, psychomotor inhibition, hypobulia, anxiety, and impatience, while they complain about physical problems such as sleeplessness and anorexia. In addition, such patients frequently complain about autonomic symptoms such as headache, constipation, and nausea. As described above, since patients with neurodegenerative diseases exhibit characteristic neurological symptoms, depressive symptoms are sometimes modified by these symptoms, resulting in the delayed detection of depressive symptoms in some patients. Initially, neurodegenerative diseases demonstrating symptoms of the extrapyramidal system tend to exhibit depressive symptoms. Such disorders, represented by Parkinson's disease, are frequently complicated by major depressive symptoms. Previously, Parkinson's disease and progressive supranuclear palsy have been initially treated with antidepressants, and the depressive state is correlative with disorders of the extrapyramidal systems. Secondly, depressive symptoms are frequently observed during the initial stage, but rarely after the middle stage of these disorders, because depressive symptoms are expressed as dementia during the advanced stage of neurodegenerative diseases. Thirdly, since neurodegenerative diseases directly demonstrate cerebral disorders, such patients frequently develop organic depressive symptoms (organic depression). That is, foregrounding hypobulia prevents the differentiation of depressive symptoms from true psychomotor inhibition, resulting in intractability and difficulty in improvement. Thus, depressive symptoms persist, and some patients with neurodegenerative diseases exhibit alteration of personality dependent on the surrounding persons. The course of depression overlaps with the basic course of neurodegenerative diseases. Although depression sometimes occurs before the initial development of neurological symptoms, the development of depression is almost always limited to during the initial and early stages of neurodegenerative diseases. However, patients with neurodegenerative diseases are rarely complicated by severe depression as is observed in those with Cotard's syndrome. Foregrounding agnosia is generally observed after the middle stage of neurodegenerative diseases. In conclusion, the brain will change in various forms according to the age of the patient, and it is necessary to comprehend each neurodegenerative disease precisely and to understand the whole range characteristics of neurodegenerative diseases when treating them in the elderly.