Alzheimer disease, a neurodegenerative disease predominantly affecting associative brain regions such as medial temporal, posterior cingulate, lateral temporal, parietal and frontal cortices, is clinically characterized by a progressive decline in memory and higher cognitive functions. Alzheimer disease patients are mainly impaired in controlled cognitive processes such as explicit memory recall, and they frequently rely on familiarity-based processes, allowing them to perform routine (automatic) activities. Moreover, personality changes and impaired judgment are typically observed in the disease.
Alzheimer disease is the most common form of dementia affecting about 5% of 65 years older and 20% of 85 years older people, and followed by vascular dementia and Lewy body disease. Other less common causes of dementia are Parkinson’s disease, alcohol abuse, normal pressure hydrocephalus, HIV infection, hypothyroidism, and deficiencies of Vitamin B12 and folic acid.
Interestingly, while behavioral disturbances are seen in more than 80% of patients suffering from these disorders, sexually inappropriate behaviors are relatively uncommon causing immense distress to patients and their caregivers.
Sexuality is not only associated with procreation or sexual intercourse, but also includes tenderness, warmth, emotion, passion, and touching, which are all important for the psycho-physical well being of the elderly.
Although general population has historically held vague assumptions and myths concerning sexual issues and practices of the older people, several studies have highlighted how they experience sexual interest and activity. Some authors have debated on the right of the elderly to have a regular sexual live indicating that institutions should not allow unmarried older people to have sexual relations or masturbation. In recent years, elderly’s quality of live is growing in importance among the general population although sexuality of older people is still marginalised in society. Health professional attitude toward sex issues of elderly is predominantly passive and conservative, since institutionalized individuals with dementia are typically unable to properly manage their sexual needs. Moreover, caregivers often have a more conservative and limiting attitude toward Alzheimer disease-patients than toward those with higher cognitive status. Nevertheless, sexuality is still important in elderly people as well as in the young, but a frequently raised question is: should two demented persons or one demented with a non-demented person be allowed to engage in a sexual relationship? The answer is still under debate, but use the safety-first rule. However, if the patients present a normal cognitive functioning and it is competent to understand a relationship, there is no resistance to let them form such relationship. However, individual’s awareness about the relationship, the presence or absence of coercion, moral values, ability to prevent abuse, and psychological aspects of entering and terminating relationships should be always evaluated.
The most frequent sexual disorder in Alzheimer disease-patients is hypersexuality or inappropriate sexual behavior. Many authors refer to these altered behaviors using the following two definitions: overt acts associated with increased libido; persistent, uninhibited, sexual behaviors directed at oneself or other people. Sexual altered behaviors are often verbal and/or physical acts with sexual meaning or intent. Patients could present with increased libido, change in orientation, sexual comments, excessive hugging/kissing, preoccupation with sex, masturbation in public, grabbing at the genitals and/or breasts of other residents or staff, sexual hallucinations, delusions of spousal infidelity, attempting to seduce other residents or staff, chasing other residents for sexual purposes, exposing one’s genitals in public, and disrobing in public. Indeed, some behaviors are thought to be inappropriate because they are performed publicly. Moreover, even when inappropriate sexual behavior is not so bouncy, it can be profoundly disruptive to caregivers and other residents in assisted living and skilled nursing facilities.
It has been shown that over 2/3 patients with dementia will have behavioral disturbances at any one point in time and that 1/3 of outpatients with dementia and 4/5 of the patients living in long-term care facilities have behavioral disturbance. Interestingly, behavioral disturbances can lead to increased morbidity, greater health care resource utilization, and premature institutionalization.
Nevertheless, epidemiological research regarding inappropriate sexual behaviors in elderly is limited. The best estimate is that 7% to 25% of demented patients exhibit altered sexual behaviors, which are more commonly found in men, although the exact sex ratios are not clear.
The brain systems implicated in the neurobiology of inappropriate sexual behaviors are the frontal lobes, the temporolimbic system, the striatum, and the hypothalamus. Each system is thought to work differently from the other, and we could predict the type of the abnormal behaviors associated with them.
The most well studied of all the brain systems is frontal lobe by far. Its dysfunction is commonly seen in dementias, multiple sclerosis, and tumors determining disinhibition rather than hypersexuality more frequently.
Animal studies have shown that sexual behaviors are also mediated through the temporo-limbic system. In humans, bilateral lesions of the temporal lobes result in Kluver-Bucy syndrome, which has been well described elsewhere in this book. Hypersexual behaviors have also been reported after temporal lobe strokes, tumors, and epilepsy. Altered sexual behaviors is more frequent after right-side temporal lesions then left-side as right lobe modulates emotion and the understanding of the affect associated with sexual arousal.
When lesions of the corticostriatal circuits occur, Alzheimer disease patients could present obsessive-compulsive behaviors. Similar behaviors can be seen in Huntington’s disease, Wilson’s disease, and Tourette’s syndrome.
Lesions involving the hypothalamus can lead to an increase in sexual behaviors; for example, Kleine-Levin syndrome is determined by bilateral hypothalamic dysfunction. Lesions to the right hypothalamus and periventricular area can cause manic symptoms including increased sexual drive.
Anamnesis with a thorough sexual history is the main part of the assessment in sexology. When the patient is severely impaired, caregivers or family members could give accurate information to clinician. It must be ensured that these behaviors are really sexual and inappropriate and do not represent a desire for closeness or comfort. It is also common for caregivers and the staff at nursing homes to misinterpret some of these behaviors as being sexually disinhibited. History-taking should be followed by a good mental status and physical examination. Laboratory data and neuroimaging examination have to be obtained to rule out delirium. Neuropsychological testing may help in evaluating the patient’s level of cognitive functioning and in understanding his or her deficits. It is important to have an open discussion about these behaviors, exploring distress they can cause and how it should be handled. The open communication and a prompt intervention are the keys to success.
Poor studies have systematically reviewed the treatment of altered sexual behaviors in patients with Alzheimer disease. The choice of treatment depends upon the urgency of the situation, the types of behaviors, and the underlying medical conditions of the patient. Both non-pharmacological and pharmacological treatments have been found to be effective.
When behaviors are due to certain misinterpreted social cues, then modification of these cues usually leads to a reduction at inappropriate behaviors. The most useful non-pharmacological treatments for those behaviors are the following:
- Behavior modification
- Supportive psychotherapy
- Changing the attitudes of the family, caregivers, and staff in the nursing homes.
Medications should only be used when all other treatment methods have failed, following the general rule of starting at a low dose and titrating slowly. Benzodiazepines are not advisable in these patients because can cause disinhibition. The classes of medications that have been found to be useful in the treatment of these behaviors include selective serotonin reuptake inhibitors (SSRIs) antidepressants, antipsychotics, and hormonal agents, along with cimetidine and pindolol.
Antidepressants. The SSRIs are found to be the best medications to decrease inappropriate behaviors. They present antiobsessional and antilibidinal effects with a high safety in overdose. Moreover, they tend to decrease sex hormone–induced aggressive behaviors and have an added benefit of treating comorbid depression and anxiety disorders . The common side effects of these drugs are gastrointestinal disturbances, headache, insomnia, and other possible sexual dysfunctions. Only cases about the use of SSRI as treatment of these altered behaviors have been reported. Therapeutical dose of paroxetine is 20 mg daily with an effect seen within 1 week and sustained at 3 –month follow-up. Moreover, citalopram (20 mg daily) is thought to be more effective than paroxetine, thanks to higher selectivity on serotonine reuptake inhibition. Also tricyclic antidepressants, such as clomipramine (at a dose of 150 to 200 mg daily), are found to be effective in the treatment of inappropriate sexual behavior in patients with dementia and exhibitionism.
Antipsychotics. The use of antipsychotics as treatment of abnormal sexual behaviors in Alzheimer disease-patients is confirmed only by clinical evidence. To date, no randomized clinical trials have been made to test their efficacy and safety. Their action seems to be related to the dopamine-blocking effect. Atypical antipsychotics are more used in clinical practice rather than typical ones, because of their better tolerance in the elderly. In a case report, an 85-year-old man affected by dementia and Parkinson the altered sexual behavior.
Trazodone. Cases of patients with dementia and inappropriate sexual behaviors responding to trazodone, after antipsychotic and benzodiazepine failure, have been described. The main side effects of trazodone, a presynaptic reuptake inhibitor and a mild postreceptor agonist of serotonin, are headache, dry mouth, sedation, orthostatic hypotension, and weight gain. Priapism is a rare complication and seems to be due to the alpha-2 blocking effect of the drug; when priapism occurs, intracavemous injection of epinephrine may be useful as emergency treatment.
Antiandrogens. The most common antiandrogens are medroxyprogesterone acetate and cyproterone acetate. They act on the reduction in serum testosterone level, which is thought to impair sexual functioning, so to eliminate the inappropriate behaviors. medroxyprogesterone acetate is a progesterone-like molecule that inhibits the levels of pituitary luteinizing hormone and follicle stimulating hormone with a reduction in testosterone blood level. The major side effects are sedation, increased appetite, weight gain, fatigue, loss of body hair, hot and cold flashes, mild diabetes, decreased ejaculatory volume, and symptoms of depression. In 1986, Cooper et al reported 4 male nursing home patients with dementia and inappropriate behaviors. Medroxyprogesterone acetate was administered at the dosage of 300mg intramuscularly per week for 1 year with a reduction of undesirable sexual activities within 10 to 14 days. The mean serum levels of testosterone and Luteinizing hormone were reduced by 90% and 60%, respectively, after 28 days, but returned to pre-treatment levels within 4 weeks after the end of the trial. At 1-year follow-up, 3 of the 4 patients were free of the inappropriate behaviors, with the forth patient presenting just some inappropriate behaviors. The investigators suggested that the effect of the drug was not only due to the reduction of the testosterone but also to its inhibitory effect on the hypothalamic neurons. To our knowledge, there is no evidence of the use of cyproterone acetate for hypersexuality in men. Only two case-reports of women with increased sexual behavior or compulsive masturbation have reported so far, with positive results.
Estrogens. The common estrogens used in clinical practice are diethylstilbestrol (DES) and conjugated estrogen. These medications act on Luteinizing hormone and Follicle-stimulating hormone secretion reducing testosterone production. Common side effects include fluid retention, nausea, vomiting, impotence, and gynecomastia. Thromboembolic episodes and increased cardiovascular events are common in patients affected by prostate cancer and treated with DES. A marked improvement in sexual abnormalities has been demonstrated in 38 out of 39 patients with dementia treated with oral estrogens or with transdermal estrogen patches.
Gonadotropin-releasing hormone analogs. These medications suppress testosterone production by stimulating the secretion of pituitary Luteinizing hormone and Follicle-stimulating hormone, leading to increased estrogen production and decreased testosterone levels. Leuprolide acetate is the common gonadotropin-releasing hormone analog used in clinical practice. Common side effects include hot flashes, erectile dysfunction, decreased libido, and irritation at the injection sites. Opportunity of using these agents for the treatment of hypersexuality in elderly is still under debate. To the best of our knowledge, only two demented patients with hypersexuality, successfully treated with leuprolide, have been reported. Problems with this drug include the inability of the subject to give informed consent, its particular side-effect profile and the ethical issue on its potential “chemical castration”.
Cimetidine. Cimetidine is an H-2 receptor antagonist with antiandrogen effects. In a retrospective study of 17 men and 3 women with various inappropriate behaviors, 14 had a good response to cimetidine at dose of 600 to 1600 mg daily. Common side effects were nausea, arthralgia, and headaches. Pindolol. Pindolol is a Sexuality in Neurodegenerative Disorders.
Pindolol. Pindolol is a β-adrenergic blockers, which seems to reduce inappropriate sexual behaviors, agitation and aggression by decreasing adrenergic drive. Nevertheless, only a 75-year-old demented man with aggressive and hypersexual behaviors responding to of 40 mg/daily of pindolol has been described so far. Time to response was 2 weeks. Common side effects of pindolol are fatigue and hypotension.
Mood Stabilizers, Cholinesterase Inhibitors (donezepil, rivastigmine, galantamine) and N-methyl D-aspartate Receptor Antagonist (NMDA) are commonly used in clinical practice as treatment of patients with cognitive impairment. Although there are no clinical evidence on the efficacy and safety of these agents on hypersexuality in AD-patients, they are thought to reduce altered behavior by improving cognitive function
Dementia is a public health problem, which is growing in importance. Behavioral problems in these subjects are very common, are considered a major source of distress and, furthermore, they represent one of the main causes of demented patient hospitalization into skilled nursing facilities.
Although inappropriate sexual behaviors in patients with dementia are not as common as other behavioral disturbances, they represent an extremely distressing and often underweighted symptom.
Early detection, prevention and a proper treatment of altered sexual behavior will reduce undue suffering to both the patients and their caregivers, as well as improve the quality of life for all those affected.