Dementia, including all of its subtypes, is one of the most common and debilitating degenerative neurologic disorders. Dementias and mild cognitive impairment are frequently undiagnosed in the elderly with the symptoms being dismissed as symptoms of normal aging. There are numerous subtypes that are categorized on the basis of etiology and pathologic findings; however, they often have similar effects on sleep. Dementia is defined as a syndrome characterized by deterioration of baseline mental function in multiple cognitive and intellectual areas with little or no disturbance of perception or consciousness. Although dementia is not necessarily an irreversible condition, most common types of dementia are permanent
and progressive. Some forms are treatable and reversible, such as those caused by thiamine deficiency, hypothyroidism, and long-standing, untreated sleep apnea.

Dementia should not be confused with delirium, a transient confusional state that is characterized by an inability to think with proper speed, clarity, and coherence, which is associated with disorientation, decreased attention and concentration, impaired immediate recall, and diminution of all mental activity. Delirium has a variety of causes, the most common of which include infection, medication side effects, alcoholic or other drug intoxication, acute drug withdrawal, and certain metabolic abnormalities. In comparison, the more common types of dementia arise from primary changes occurring within the brain cells. Although the symptoms of most types of dementia develop over the course of months to years, delirium typically arises over hours to a few days and may last several weeks. The initial signs and symptoms of delirium usually include decreased concentration, irritability, tremulousness, insomnia, and poor appetite. The patient will typically describe vivid and unpleasant dreams that are further complicated by transient illusions and hallucinations during wakefulness. Convulsions are relatively common, occurring in approximately one-third of cases. Later in the course of the condition, patients may experience paranoia, tremor, insomnia, and autonomic hyperactivity. Unlike dementia, recovery from delirium is usually complete and heralded by increased lucid intervals and sound sleep.

In contrast, dementia is conventionally said to involve impairment in memory and at least one other cognitive sphere (i.e., language, praxis, or the ability to perform simple tasks; calculation; judgment; visuospatial orientation; abstract thinking; concentration, etc.). There may be behavioral abnormalities and personality changes with little or no disturbance of consciousness or perception. Delirium and dementia may coexist, and, in fact, because of diminished brain function, patients with dementia are at increased risk of developing delirium from minor infections, changes in medication, and so forth. This may further complicate the treatment of sleep disorders.

Alzheimer’s disease (AD) is the most common cause of degenerative dementia and is estimated to be the etiology in 60% to 80% of patients. The figures are not exact since a definite diagnosis of AD requires detection of characteristic lesions on postmortem examination of brain tissue. For this reason, clinical trials and studies of AD have likely contained significant numbers of patients with other dementia subtypes.

AD occurs with equal frequency in men and women and usually begins after the age of 60 years. Risk factors include advanced age; family history; Down’s syndrome (essentially all patients with Down’s syndrome who are older than 35 years have AD); low educational level; chromosomal mutations on chromosomes 1, 14, and 21; apolipoprotein E ε-4 genotype; and a history of brain injury. Regardless of the cause, AD is characterized by decreased levels of the neurotransmitter acetylcholine in the hippocampus and neocortex due to loss of cholinergic projections from the nucleus basalis of Meynert. The clinical features of AD include a gradual decline in intellectual function, poor short-term memory with relative sparing of long-term memory in the early stages of the disease, visuospatial disorientation, language/speech problems, and personality changes. Patients develop difficulty performing simple tasks, including activities of daily living such as eating, drinking, and walking. New-onset seizures occur in approximately 10% of patients with AD.

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia, representing approximately 15% to 20% of cases. It occurs twice as often in men than in women, with symptom onset typically between the ages of 50 and 80 years. The hallmark pathologic feature in brain tissue is, of course, Lewy bodies, which are inclusions seen within neurons. The clinical features of DLB include dementia, psychosis, and mild extrapyramidal symptoms such as spasticity. The presenting symptoms are usually personality changes and behavioral problems followed by deterioration of memory over months to years. Hallucinations and delusions are common.

Pick’s disease is one of the dementias that is associated with a loss of neurons in the frontotemporal region of the brain. It is a rare degenerative dementia comprising <10% of the patients with dementia. Unlike DLB, it occurs more frequently in women than in men. The onset of symptoms is typically in the sixth decade of life. The hallmark pathologic features, Pick bodies, are cytoplasmic inclusion bodies that are present in affected neurons. Similar to DLB, the clinical features of Pick’s disease include personality changes and behavioral problems usually associated with poor judgment. There is a gradual decline in intellectual function and poor short-term memory. Patients may develop Kluver-Bucy syndrome, which is characterized by hypersexuality, hyperorality, and docile behavior.

Vascular dementia is the cause of approximately 10% of cases of dementia. It occurs in patients with a history of stroke and cerebrovascular disease. As with other types of atherosclerotic vascular disease, it is more common in men. Since stroke and cerebrovascular disease are so common, vascular factors may also complicate other dementia subtypes. Vascular dementia can be caused by ischemic stroke, cerebral hemorrhage, anoxic/ischemic brain injury,
or vasculitis. Unlike AD, which has a gradual cognitive decline, there is typically a stepwise progression of symptoms associated with each new vascular event.

There is speculation that sleep-related breathing disorders may be one of the underlying factors contributing to vascular dementia, but definitive data regarding this relationship are lacking at present. In general, the effect of restful sleep versus unrefreshing sleep on the dementias is poorly understood. Untreated or inadequately treated obstructive sleep apnea/hypopnea in the general population causes excessive daytime somnolence, depressed mood, decreased quality of life, and subsequent cognitive dysfunction. Treatment of obstructive sleep apnea can improve this cognitive dysfunction (1,2,3 and 4). Treatment with positive airway pressure in neurologically intact individuals improves attention, speed of thinking, short-term memory, and general cognitive status (3,4 and 5). There is limited data regarding the effect of sleep apnea treatment on the cognitive status of patients with degenerative dementia; however, our experience has been that many patients will receive some benefit. We have also found that many patients with dementia tolerate CPAP therapy quite well.

Another important consideration is that treatment of sleep disorders improves the bed partner’s (and usually the primary caregiver’s) quality and amount of sleep (6). Theoretically, improvement in the quality of sleep can result in some improvement in the patient’s level of cognitive function, and so diagnosis and correction of any underlying sleep disorder is desirable, for the benefit of both the patient and his or her bed partner.

There are case reports of patients diagnosed with delirium or dementia whose cognitive dysfunction improved markedly following treatment of previously untreated obstructive sleep apnea. Sleep-related breathing disorders should be considered a potentially reversible cause of dementia.

Patients with DLB appear to have a greater risk of rapid eye movement (REM) behavior disorder (RBD), although the prevalence is not yet known (7,8 and 9). In fact, it is so common that RBD is now regarded as a supportive feature for the diagnosis of DLB (10). The relationship between RBD and neurodegenerative disease suggests an underlying synucleinopathy (a group of disorders that includes DLB, multiple system atrophy [MAS], and Parkinson’s disease). The RBD typically begins years prior to the onset of other symptoms of dementia. The differential diagnosis for the abnormal behaviors includes RBD as well as epileptic seizures and wandering, behavior that commonly occurs in the population with dementia. Episodes of wandering are usually less violent, do not appear to be associated with REM sleep, and are often of longer duration than a typical REM period. Polysomnography with video monitoring, a full electroencephalogram (EEG) montage, and additional electromyogram leads on all four extremities can help confirm the diagnosis of RBD. Clonazepam is the drug of choice in treating RBD and is effective in the majority of cases (11). If clonazepam proves ineffective or is not tolerated, alternative treatments include carbamazepine (12), donepezil (13), and dopamine agonists.

The epidemiology of restless legs and periodic limb movements in patients with degenerative neurologic disorders is not well understood. Restless legs syndrome (RLS) is quite common, occurring in at least 10% of the population who are generally affected by degenerative cognitive disorders.