Dementia, including all of its subtypes, is one of the most common and debilitating degenerative neurologic disorders. It is frequently undiagnosed in the elderly, with the symptoms dismissed as normal aging. There are numerous subtypes which 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/intellectual areas with little or no disturbance of perception or consciousness. Dementia is not necessarily an irreversible condition. Although 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 which is characterized by an inability to think with proper speed, clarity, and coherence, and which is associated with disorientation, reduced 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 in a substance abuser, and metabolic abnormalities, which complicate liver failure, renal failure, etc. 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 reduced concentration, irritability, tremulousness, insomnia, and poor appetite. The patient will typically describe vivid and unpleasant dreams, which are further complicated by transient illusions and hallucinations during wakefulness. Seizures are relatively common, occurring in approximately one-third of cases. Later in the course of the condition, patients may experience paranoia, tremor, 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 (language, praxis or the ability to perform simple tasks, calculation, judgment, visuospatial orientation, abstract thinking, or concentration). There may be behavioral abnormalities and personality changes with little or no disturbance of consciousness or perception. Delirium and dementia may coexist, and because of diminished brain function, patients with dementia are at increased risk of developing delirium from minor infections, changes in medication, etc.

Alzheimer disease (AD) is the most common cause of degenerative dementia and is estimated to be the etiology in 60% to 80% of patients with dementia. The figures are not exact because 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 60 years of age. Risk factors include advanced age, family history, Down syndrome (essentially all patients with Down syndrome who are over 35 years of age have AD), low educational level, chromosomal mutations on chromosomes 1, 14, and 21, apolipoprotein E ε4 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 because of loss of cholinergic projections from the nucleus basalis of Meynert. The clinical features of AD include a gradual decline of 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 Alzheimer patients.

More recently, obstructive sleep apnea syndrome has been related to AD. The degree of the impact of obstructive sleep apnea syndrome on the development and progression of AD continues to be a topic of research.

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 as in women. The onset of symptoms typically begins between 50 and 80 years of age. The hallmark pathologic feature in brain tissue is 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 disease is one of the dementias that is associated with loss of neurons in the frontotemporal region of
the brain. It is a rare degenerative dementia occurring in less than 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 of Pick bodies are cytoplasmic inclusion bodies which are present in affected neurons. Similar to DLB, the clinical features of Pick disease include personality changes and behavioral problems usually associated with poor judgment. There is a gradual decline of 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. Because 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.

Dementia patients have the same risk of developing sleep disorders as the general population. 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, reduced quality of life, and subsequent cognitive dysfunction. Treatment of obstructive sleep apnea can improve this cognitive dysfunction (1, 2, 3, 4). Treatment with positive airway pressure (PAP) in neurologically intact individuals improves attention, speed of thinking, short-term memory, and general cognitive status (3, 4, 5). There are limited data regarding the effect of sleep apnea treatment on the cognitive status of patients with degenerative dementia, yet our experience has been that many patients will receive some benefit. An 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, so diagnosis and correction of any underlying sleep disorder is desirable for the benefit of both the patient and his or her bed partner.

Patients with DLB appear to have a greater risk of rapid eye movement (REM) sleep behavior disorder (RBD), although the prevalence is not yet known (7, 8, 9). RBD is so common that it is now regarded as a supportive feature for the diagnosis of DLB (10). RBD typically begins years before the onset of other symptoms of the dementia. The differential diagnosis for the abnormal behaviors includes RBD as well as epileptic seizures and wandering, behaviors that commonly occur in the demented population. 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 electromyography 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 melatonin, carbamazepine (12), donepezil (13), and dopamine agonists. Aggressive treatment of any underlying sleep-related breathing disorder is extremely important in the management of RBD.

The epidemiology of restless legs and periodic limb movements (PLMs) 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.

Restless legs may occur as a genetic disorder, or may be secondary to arthritis, peripheral vascular disease, peripheral neuropathy, or relative iron deficiency. A number of medications have shown efficacy for the treatment of restless legs, including ropinirole, carbidopa/levodopa (L-dopa), pramipexole, benzodiazepines, opiates, pregabalin, and gabapentin enacarbil, but some of these medications should be used cautiously in the demented population. L-Dopa has been associated with augmentation of symptoms, a paradoxical worsening of the frequency and severity of symptoms related to the medication itself, as well as an increased risk of psychosis and insomnia. Dopamine agonists (pramipexole and ropinirole) have a lesser risk of augmentation but can be associated with an increased risk of psychosis, insomnia, and the possibility of inappropriate sleepiness. As sedatives or central nervous system depressants, benzodiazepines and opiates can help overcome restlessness but may have unacceptable cognitive consequences in patients with dementia. Likewise, the antiepileptic
medications can also have adverse cognitive side effects. Patients who have decreased levels of serum ferritin may experience a sufficient reduction in symptoms with iron replacement such that medication may be unnecessary. It is uncommon for patients without RLS to experience PLMs during wakefulness; however, PLMs occur during sleep in about 80% of patients with RLS. PLMs are more common in the normal elderly population (14) than in younger individuals. PLMs without associated sleep disruption should not be treated, especially in patients with dementia who are more likely to have adverse medication side effects.