Robert J. Pary, M.D.
Associate Professor of Psychiatry
Southern Illinois University, School of Medicine
P.O. Box 19230
751 Rutledge Street
Springfield, IL 62794-9230
The Habilitative Mental Healthcare Newsletter
1992, Vol. 11, No. 6, p. 37-41.
© 1992 Pysch-Media, Inc.
Reprinted with permission of Psych-Media, Inc., publishers of Psychiatric Aspects of Mental Retardation Reviews, Habilitative Mental Healthcare Newsletter, and the journal Mental Health Aspects of Developmental Disabilities.
Editor-in-Chief: Anne D. Hurley, Ph.D
P.O. Box 57
Bear Creek, NC 27207-0057
Fax: (336) 581-3766
Dementia is a syndrome of memory loss plus: a) an impairment in judgement; b) a personality change; or c) a loss of higher cortical functions (i.e., losing ability to dress oneself despite having sufficient motor strength to do so) resulting in an overall decline in functioning.1 Alzheimer's disease is a progressive form of dementia characterized by certain changes in the brain and results in a total inability to care for self and eventually to death. To date, no clinically accepted treatment can reverse the illness. Alzheimer's disease can be complicated by depression or delusions which may respond to psychoactive medications. Unfortunately, the diagnosis of Alzheimer's disease can only be confirmed at autopsy.
DS and Alzheimer Disease
More than a century ago, Fraser and Mitchell observed "precipitated senility" in patients with DS.11 The link between Alzheimer's disease and DS was underscored when Wisniewski et al found that almost all individuals with DS, who die after 35 years of age, show evidence of Alzheimer-like changes in their brains.48 A relationship between DS and Alzheimer's disease is now accepted. 2,5,15,21 Clinically, however, dementia is not seen in everyone with DS after age 35. Alzheimer-like changes can be seen in brains of nondemented elderly in the general population.4,5
Lai and Williams reported the prevalence of dementia in a mixed institutional and community population of DS individuals over the age of 35.23 About half (51%) had dementia with an average age at the onset of dementia to be 54.2 ± 6.1 years (range 43-68 years). Dementia occurred in two of 25 subjects between ages 35-49 years, 11 of 20 between 50-59 years, and 6 of 8 over 60.
The initial phase of dementia in the higher functioning individuals was a personality change (e.g., irritability or mood lability), memory impairment, spatial disorientation (e.g., getting lost in the residence), or reduced talking. In the group, which had more severe disabilities prior to the onset of dementia, the first indications were apathy (lack of interest in previously enjoyable activities), inattention, and decreased social interaction. (As will be discussed later, the early signs of dementia such as a lack of interest and reduced social interactions can also be seen in depression.13)
In the second phase of the dementing process, there was loss of ability to dress, use eating utensils, and toilet oneself. Also, gait became slow and shuffling, and workshop activity nonproductive. Seizures frequently occurred as well.
Oliver and Holland reviewed eight articles with case reports describing the clinical changes in 14 individuals with DS and Alzheimer neuropathology.28 Nine of the 14 had "apathy", "depression", "lethargy", "withdrawn" or "lost interest". The authors concluded that clinical changes involved behavioral deterioration, loss of self-care skills, or loss of language.
Evenhuis also described the clinical course of 14 patients with DS and dementia (mean age of onset 51.9 years, range 45 to 60 years).9 In the initial phase, 13 of 14 had apathy and withdrawal, 9 had loss of self-help skills, 7 had daytime sleepiness, and 6 had gait deterioration. Myoclonus (brief, shock-like jerks), urinary incontinence, and seizures occurred at different phases depending on level of developmental disabilities. These symptoms were seen early, if the patient had severe disabilities, and usually not until after the second year in those with moderate disabilities.
TABLE 1. DIFFERENTIAL DIAGNOSIS OF FUNCTIONAL DECLINE IN DS
Disorders Which Are Common in DS
- infection folate or B12 deficiency
- hearing impairment
- visual impairment
- malignancy such as leukemia
- joint problems of the neck, knee or hip
- Alzheimer disease
- (?) sleep apnea
Miscellaneous Cerebral Conditions With No Apparent Predilection for Individuals with DS
- subdural hematoma
- brain tumors
- normal pressure hydrocephalus
Differential Diagnoses of Functional Decline
Table 1 lists the differential diagnoses of functional decline in adults with DS.
Hypothyroidism can cause a decline in functioning by reducing one's energy, motivation, and enthusiasm, and by causing mental slowing. Thyroid disease is common in DS. Mani studied 55 patients ranging in age from 24 to 67 with a mean age of 43.3 years, and found that 50% had clinical features compatible with hypothyroidism and 22% (12 patients) had the disease.25 All 12 were 39-years or older. Dinani and Carpenter found that of 106 adults with DS, 43 (40.5%) had abnormal thyroid function; over 60% were 35-years or older.8
Weight loss, withdrawal or loss of interest, sleep difficulty, tearfulness, anxiety, irritability, and depressed mood are commonly reported in case reports of depression in DS.6,19,24,29,32,35,37,42,47 Nevertheless, Sovner has emphasized that standard diagnostic criteria used in the general population may need to be modified for individuals with developmental disabilities.36 One feature of major depression in the developmentally disabled may be a loss of activity of daily living skills such as the onset of urinary incontinence. What emerges from the case reports and Sovner's criteria is that major depression, in this population, is characterized by withdrawal, a mood disturbance, and loss of personal care skills.
The difficulty in diagnosing major depression from dementia is illustrated by Reid's description of a 50-year-old man with DS, who became "withdrawn and unsociable" and underwent what appeared to be a personality change.30 He started to sleep poorly and began to get up at night. Soon after he became ... incontinent [of urine and feces], progressively less capable of fending for himself, and terminally he began to eat rubbish ...he died at the age of 53... Changes characteristic of severe Alzheimer's disease were present in all sections of cerebral cortex examined microscopically. As noted above, Oliver et al,28 Lai et al,23 and Evenhuis have commented that depression, lethargy, personality change, withdrawal and loss of self-help skills often occur in individuals with DS and Alzheimer disease.
Szymanski and Biederman mentioned that depression and dementia can coexist.37 This view is supported in studies of the general population.31,33 Zubenko et al have detected neurochemical changes in the brains of individuals with primary dementia who had depression that differed from those that had only primary dementia.49 Rovner et al found that the "subgroup of patients with Alzheimer's disease and depression were more cognitively impaired and more socially disabled than nondepressed patients.33 Jenike noted the benefit of monoamine oxidase inhibitor therapy for two patients with major depression and Alzheimer's disease, who did not benefit from standard antidepressants.20 Their improved mood allowed these patients to have a better quality of life despite the progressive memory loss.
It appears that symptoms of major depression should be treated in individuals with DS, even if dementia is also suspected. Furthermore, it appears that the failure to respond to a single antidepressant agent may be inadequate to rule out depression. Jenike's case studies offer support for at least a second course of therapy with a different antidepressant in unresponsive individuals suspected of having depression.20
TABLE 2. WORK-UP FOR FUNCTIONAL DECLINE IN DS
- sleep and weight graphs
- vital signs
- complete blood count
- screening blood chemistries
- thyroid function tests
- folate and B12 levels
- chest X-ray
- brain imaging study
- neuropsychological testing
- assessment of daily living skills
- graph of work productivity
- consider the following consultations:
- (?) sleep laboratory
As one's eyesight or hearing significantly worsens, overall functioning may deteriorate. Unfortunately, adults with DS are at risk for both visual and auditory impairment.
Keiser et al estimated that 40 to 77% of persons with DS suffer from the hearing loss.22 They concluded that adults with DS are prone to a variety of ear problems and may benefit from otological/audiological consultaion.
In addition, up to 46% of patients with DS reportedly have cataracts.17 Odell has advised that cataracts should be ruled out as a cause for deterioration before diagnosing Alzheimer's disease.27
Older adults with DS have impaired white blood cell function and are, therefore, susceptible to infection.26 It is not surprising that a leading cause of death in individuals with DS is pneumonia.7,41 At times, pneumonia will present as increased lethargy or confusion before clear respiratory signs appear. Useful clues include fever, rapid heart beat, increased respiratory rate, or elevated white blood cell.46
In the general population, vitamin B12 deficiency can cause confusional syndromes and dementia.46 Although vitamin B12 deficiency has not been reported in adults with DS, Cartlidge and Curnock described a 3-year-old girl with DS who was lethargic, irritable, had decreased appetite with weight loss, and withdrawal.3 She was found to have malabsorption of vitamin B12 and all of her symptoms disappeared following hydroxycobalamin therapy.
Another potential cause for decline in functioning in individuals with DS is sleep apnea.34,39 Apnea is a temporary cessation of breathing and can cause excessive daytime sleepiness, lethargy and irritability. The diagnosis, however, may be difficult to confirm because many individuals with DS will not tolerate sleeping all night in a laboratory connected to a machine.
Adults with DS are susceptible to joint problems in the neck, knee or hips.4,38 Joint pain may cause a decline in functioning by making it difficult to walk. This can result in reduced activity levels. An orthopedic consultation may be indicated if there are gait, posture or neck symptoms (neurologic consultation if the neck is involved).
Leukemia occurs more often in adults as well as children with DS than in the general population.27 This blood cell cancer can present as tiredness, weight loss and an overall decline in functioning before the diagnosis is made. Cardiac disease can also produce a functional decline.12
In addition to a history and physical examination. Table 2 lists a suggested work-up for functional decline in adults with DS. The work-up emphasizes ruling out three potentially reversible conditions of functional decline: infection; thyroid disease; and depression. A brain imaging study (computerized tomography or magnetic resonance) should probably be attempted to rule out tumors or other conditions such as subdural hematomas (clotted blood under the lining of the brain) all of which can lead to confusion, dementia and a decline in functioning.
The clinician should consider audiologic, ophthalmologic, orthopedic, and possibly sleep laboratory consultations depending upon clinical circumstances. It is also important to establish the baseline level of psychosocial functioning through neuropsychological testing. Psychological testing, e.g., the Thematic Apperception Test, can be helpful in diagnosing depression (especially when baseline test results are available for comparison). An assessment of daily living skills and work productivity should also be included. These evaluations can help determine whether an intervention (e.g. an antidepressant trial) has had any impact on the decline.
Functional decline in a person with DS does not necessarily presage the onset of a progressive and irreversible dementing process. A careful consideration of other reversible causes of impaired psychosocial function can provide persons with DS many years of meaningful life.
|Revised: May 18, 2000.|