Mood, anxiety, and thought disorders are not uncommon in adults with DS [32], with a combined frequency of 10%–20% in young and middle age adults. A possible relationship between depression and dementia in adults with DS has also been noted [33] but remains understudied (see Chapter 14).

Presentation

Elderly adults without dementia demonstrate fewer and less severe maladaptive behaviors than those with early or mid-stage dementia. The maladaptive behaviors associated with progression into early stages of dementia may include aggression, fearfulness, sadness, sleep problems, and other regressive behaviors [34]. Psychiatric symptoms are often apparent and may include delusions, hallucinations, and depression with associated appetite and sleep problems [35].

Evaluation and management

Medical and psychiatric assessment should ensue for those experiencing sudden changes in behavior or mental health function. Evaluation and management needs to be coordinated by physicians familiar with the range of medical and mental health conditions experienced by adults with DS. Problems including dehydration, infection, hypothyroidism, and severe sleep apnea should be considered as should the potential harms of polypharmacy and overreliance on psychotropic medications to manage maladaptive behavior.

Though little research exists, it is known that obstructive sleep apnea (OSA) is much more prevalent in adults with DS than previously thought. An extraordinarily high prevalence of hypopnea and apnea associated with oxygen desaturation was reported in several studies [36–38]. Most caretakers and the adult individuals themselves are either unaware or do not self-report nighttime symptoms [39]. A relationship between apnea score and performance on cognitive testing has been noted [36]. The risk for OSA in adults is increased due to both upper airway anatomy and obesity. A recent study reported that 94% of adults with DS had abnormal polysomnograms, with 70% indicating severe OSA (apnea-hypopnea index (AHI) > 30) [38]. There was a clear correlation between BMI and AHI, but not for age and AHI or hypothyroidism and AHI. In a study by Resta et al. [37], increasing age was found to be the strongest risk factor in predisposing adults to OSA, especially if other risk factors were not present. However, a study comparing adults (< 50 years) to those (> 50 years) revealed no increase in the frequency of OSA [21].

Presentation

Severe sleep apnea can lead to daytime symptoms suggestive of major depression, cognitive decline, and a pseudo-dementia like picture [40]. When functional decline is seen in adults at any age, evaluation and treatment for OSA should be considered before concluding that the patient has dementia. Other common daytime symptoms of OSA include trouble concentrating, fatigue, and mood changes (irritability, internalization, and social withdrawal). Nighttime symptoms may be less noticeable and even loud snoring may be absent. Other signs include witnessed pauses in breathing, sudden nighttime awakenings, gasping or choking, excessive sweating, urinary incontinence, or difficulty awakening in the morning.

Evaluation and management

Overnight polysomnography (PSG) should be performed as a routine part of the diagnostic evaluation in any symptomatic individual who has obvious snoring, witnessed respiratory pauses, or significant daytime symptoms. However, overnight PSG is not well tolerated by many individuals with DS and often proves a frustrating endeavor for the patient, family, and physician alike. Without a confirmatory diagnosis there is no treatment offered and chronic, persistent cognitive and mental health problems may continue. In asymptomatic patients, PSG may be indicated when additional risk factors such as obesity or a crowded, partially obstructed orohypopharynx is present. Macroglossia, lingual tonsils, and glossoptosis are all common reasons for persistent OSA in adults [41]. Referral to sleep medicine and/or ENT should be made, given that chronic, untreated OSA can lead to irreversible cardiopulmonary and cognitive changes. CPAP or BiPAP poses a challenge to many individuals and adherence may be quiet low. Some individuals comply well with CPAP after realizing the general benefits of feeling better. Surgical treatment may include consideration of lingual tonsillectomy, UPPP, and tracheostomy.

Clinicians must consider the feasibility and burden of performing diagnostic testing (overnight polysomnogram) and the likelihood that standard therapeutic recommendations (CPAP/BiPAP or UPPP) will be acceptable to the individual and caretaker alike. Caretakers may decide to forego diagnostic evaluation in the belief that currently available therapies will not be adhered to or will only place added burden on themselves when trying to enforce adherence. A frank and open discussion with the patient and caretakers about these issues is required.

Weight reduction may help to reduce the work of breathing and the severity of symptoms. Positional therapy (sleeping upright, reclined, or in sidelying) may help to minimize airway obstruction.

Other considerations

Gastroesophageal reflux can also result in symptoms of coughing or choking during sleep and should always be considered. Pulmonary hypertension, poorly controlled asthma, or nasal-sinus congestion can also exacerbate OSA when present. Other causes of sleep disturbance such as seizures, PLMD, or parasomnias are occasionally seen.

Persons with DS experience presbycusis or progressive bilateral sensorineural hearing as they age during adulthood [42]. Research indicates that at least two-thirds of DS adults aged 35 years or older have a component of sensorineural hearing loss of greater than 20 dB with relatively low rates (5%–10%) of isolated conductive hearing loss [19,43]. Almost half of adults in this study showed evidence of mixed conductive and sensorineural loss. In addition to the increasing rate of hearing loss, there is evidence that severity increases with age with about three-fourths of older adults estimated to have moderate-profound hearing loss. An association between dementia and high rates of hearing impairment has also been noted [44].

Presentation

Hearing loss in DS can be somewhat difficult to detect given that patients do not often communicate that they are having difficulty hearing. Patients with hearing loss may present with apparent confusion or decline in function, social withdrawal, decreased responsiveness, or the appearance of stubbornness. Hyperacusis, tinnitus, and vertigo do not appear to accompany hearing loss at high rates in this population, but this is difficult to confirm. A study by Van Buggenhout et al. [19] revealed that 80% of primary care providers to patients with DS were unaware of their hearing loss.

Evaluation and screening

It is important to regularly screen and monitor all adults for hearing loss. This should be done every 1–2 years in asymptomatic adults or sooner with any change in functional status. Particular testing should be directed by an audiologist and may include pure tone and speech audiometry in mild-moderate intellectual disability (ID) or free field audiometry (behavior observation audiometry) for persons with more severe ID. Impedance tympanometry is often incorporated to assess tympanic membrane mobility.

Management

Management of sensorineural hearing loss may include hearing aids and consideration of cochlear implants, though this should be directed by the patient’s prognosis for functional improvement and likelihood for compliance. In individuals with conductive or mixed hearing loss, it is important to consider causes such as ossification of middle ear bones and cerumen impaction of the external canal. Some individuals benefit from regularly scheduled cleaning of the external ear canal to prevent impaction. Practical measures such as avoidance of loud environments, assuring that joint attention is established prior to conversation and using simple language or gestures to supplement verbal instruction, are usually helpful.

Aging persons with DS have a high risk of developing visual impairment, cataracts, and keratoconus. Mild visual impairment is estimated to affect over 50% of older adults. Moderate vision impairment is seen in 21% while severe impairment effects 9% [19]. As with hearing impairment, the prevalence and severity of visual impairment both increase with advancing age. Cataracts contribute to the high rates of visual impairment and are experienced by (30%–68%) compared to the general population (17%) [45]. In addition to the classic “senile cataracts” there is an increased prevalence of “coronary cerulean cataracts,” which are flake-like lens opacities scattered throughout the peripheral cortex of the lens [46]. Finally, keratoconus (degeneration of the cornea) also contributes to vision problems. Keratoconus also increases in prevalence with age, occurring in 20%–37% of elderly DS individuals compared to 11% in middle-aged DS patients [18,45]. A recent cohort study reported lower prevalence rates of about 3% in adults [47].

Presentation

As with hearing loss, visual impairment may be difficult to detect due to lack of awareness and self-reporting. However, the same type of symptoms, including confusion, decline in visual-motor function, withdrawal, decreased responsiveness, or the appearance of being stubborn. Additionally, individuals may develop anxiety and apprehension, increasing falls, or apparent clumsiness.

Evaluation and screening

Visual acuity should be screened every 2 years in asymptomatic adults, or sooner with any change in visual-motor function. The primary practitioner should not wait for spontaneous complaints or observations of caregivers as vision loss may be subtle, unnoticed, or underreported. As with hearing evaluations, visual acuity and ophthalmic evaluation methods depend in part on functional level. The Landolt ring chart and Burghardt picture charts can be used in individuals with moderate-severe intellectual impairment. Direct observation and registration of eye movements and eye contact may be utilized in those with more profound impairment.

Management

Visual acuity should be assessed by an ophthalmologist experienced in the care of elderly persons with ID. Simple visual acuity deficits should be addressed with corrective lenses and patching. In the case of cataracts with visual impairment, the practitioner, patient, and caretakers must carefully weigh the risks and potential benefits of cataract surgery. It has been suggested that not all cases warrant surgery given that visual impairment may persist due to aphakia or poor compliance with use of bifocals in this population. Cross-linking procedures have also been approved and are being used in the early stages [48]. In the case of severe keratoconus, corneal transplant could be considered. Keratoconus may be exacerbated by frequent rubbing of the cornea when an individual experiences dryness or itching, and thus may be preventable when these symptoms are treated successfully.

Thyroid abnormalities also occur with increased prevalence in adults with DS. It has been postulated that there is an increasing risk for developing hypothyroidism with advancing age as evidenced by higher thyroid-stimulating hormone and declining thyroxine levels [49]. However, a study by Van Buggenhout found no significant correlation between advancing age and increased TSH levels [19]. In a study by Kerins (2008), 35%–40% of DS individuals over 50 years were diagnosed with abnormal thyroid function, though only around 8% actually had active, clinically significant hypothyroidism [21,50].

Presentation

Clinical symptoms of hypothyroidism may be difficult to detect in adults with DS because many of the same symptoms are common in DS itself. However, thyroid dysfunction should be evaluated in any patient presenting with typical symptoms of hypothyroidism, cognitive decline, depression, or general slowing.

Evaluation and management

It is generally recommended to check serum TSH and T4 levels on an annual basis in asymptomatic individuals. If clinical hypothyroidism is confirmed thyroid autoantibodies (TPO, TGB, TSI) should be checked as well. Autoimmune disease (Hashimoto’s thyroiditis) is common and may prompt screening for other common autoimmune disorders. Hypothyroidism (elevated TSH, low T4) is typically treated with levothyroxine and requires routine monitoring. Some experts argue for treatment of subclinical hypothyroidism (elevated TSH with normal T4) to prevent progression to frank hypothyroidism, with anecdotal reports of improved physical and mental well-being [19].

Peripheral vascular disease and atherosclerosis

Adults with DS appear to have lower rates of atherosclerosis compared to control groups, as seen on autopsy [55]. They seem to have fewer risk factors for the development of coronary artery disease as well [56]. In a study of 141 adults with DS (ages 30–65), very low rates of hypertension (3%) and hypercholesterolemia (9%) were found, both far below rates seen in the general population [21]. DS individuals may be relatively resistant to developing atherosclerosis, possibly due to reduced heart-type fatty acid binding protein (Vianello et al. 2013). It has been noted that adults with DS may have higher rates of embolic stroke but reduced risk for ischemic strokes compared to the general population [7,56]. The prevalence and type of cerebrovascular disease experienced by adults with DS and associated risk or protective factors requires further study.

Autonomic function

Adults with DS generally have lower resting heart rates and blood pressures compared to the general population, and essential hypertension is uncommon [50]. However, a study comparing adults (< 50 years) to those (> 50 years) revealed increased use of antihypertensive medications (4% vs 19%) in the older adults [21].

Chronic hypotension appears to be common and is often associated with other signs of autonomic dysfunction including mottling or acrocyanosis of the peripheral extremities. In asymptomatic individuals, screening consists of monitoring heart rate and blood pressure for bradycardia and hypotension. Symptomatic individuals will often have a history of syncope or presyncopal episodes, orthostatic changes, and spells or falls. Orthostatic BP changes should be measured, and the individual referred for a Tilt-Table test. Initial preventive measures include maintenance of adequate hydration status, added salt to the diet, and caution upon prolonged or sudden standing.

Menopause typically occurs earlier in women with DS compared to the general population. Women with DS have a median age of menopause 4–6 years earlier than general population. In a study by Schupf, 87% of women with DS stopped menstruating by age 46 years and 100% had cessation by age 51 years [57]. The median age of menopause in DS (47.1 years) is 2 years younger than in women with ID (49.3 years) and 4 years earlier than the average age of menopause in the general population (51.3 years) [58]. Earlier menopause in women with DS has been associated with a 1.8-fold increased risk of dementia (hazard ratio 1.82) and with increased risk of death (hazard ratio 2.05) [59,60].

Presentation

In women with DS, menopause presents as it does in the general population, though many women with DS may not report symptoms or may have difficulty describing their experiences, such as hot flashes and vaginal dryness. With the onset of menopause, practitioners should be increasingly vigilant of screening for osteoporosis, mental health issues, and dementia.

Evaluation and management

There are no screening guidelines for asymptomatic adult individuals. Management of menopausal symptoms in women with DS does not vary appreciably from those in the general population. Individuals may be referred to Gynecology for further evaluation. Serum estrogen, testosterone, LH, and FSH may be confirmatory. Topical estrogen creams can be prescribed for vaginal dryness. Hormone replacement therapy has not been studied.

Reduction in bone mass density (BMD) has been documented in middle-aged adults with DS. Factors related to reduced BMD may include early menopause, hypogonadism, hypotonia, low muscle strength, reduced mobility, antiepileptic medication use, and reduced sunlight exposure [61,62].

Presentation

When adjusted for bone and body size, adults with Down syndrome demonstrated a lower volumetric BMD in lumbar spine and diminished bone strength relative to the loads that the femoral neck must bear [63]. Recent evidence suggests that diminished osteoblastic bone formation and inadequate accrual of bone mass, without differences in bone resorption, may be an underlying mechanism regardless of gender or other risk factors [64].

Evaluation and management

While there are no established screening guidelines for asymptomatic adult individuals, some clinicians obtain a DXA bone density scan between 40 and 50 years or sooner in menopausal women. Monitoring of vitamin D levels in younger adults may be indicated. Preventive measures may include weight-bearing activities, sunshine, vitamin D, and calcium supplementation [65]. The effectiveness of treatment for symptomatic individuals using bisphosphonates and other antiresorptive therapies has been questioned [64].

The onset of seizure disorders in DS occurs within a bimodal distribution, most often seen during childhood and later adulthood/senescence. During adulthood, the risk of seizures increases with advancing age, especially in the setting of dementia. In older adults over 50 years of age, between 24% and 46% have seizures [68,69]. One study comparing individuals with DS (< 50 years) to those (> 50 years) documented increased use of anticonvulsants in the older group (16% vs 38%) [21]. Two studies have documented abnormal EEG findings in ~ 70% of elderly DS adults independent of seizure status [70,71]. There was no apparent relationship between severity of EEG changes and dementia.

Presentation

Seizure disorders among elderly DS individuals often forebode the onset of dementia. In studies by Lott and McVicker, 53%–80% of adults with new-onset seizures also had symptoms of dementia or experienced the onset of cognitive decline soon afterward [69,72]. The seizures associated with dementia are often myoclonic jerks which may be prominent upon or soon after awakening, and are sometimes asymmetrical [73]. Of the 18 patients that presented with myoclonic jerks, 14 (78%) also developed generalized clonic-tonic seizures.

Evaluation

Screening of asymptomatic elderly individuals may be done by taking a good history from a knowledgeable caretaker. Episodic events that may be confused with seizure need to be ruled out, such as bradycardia/hypotensive episodes resulting in syncope (common), cardiac conduction abnormalities (AV canal repair), or gait disturbance resulting in frequent falls. For symptomatic adults presenting with an initial seizure a standard workup should be pursued. It is important to determine whether an actual seizure occurred, which is best elucidated through a careful history suggesting generalized clonic-tonic or myoclonic movements. Urinary incontinence, tongue biting, postictal fatigue, and lack of memory of the event can be revealing bits of history. If there is high suspicion for seizures, referral to a neurologist is warranted with pursuit of brain imaging (CT, MRI) looking for evidence of an acute stroke-like event, hydrocephalus, or chronic atrophic changes. Standard or extended EEG should be performed to confirm epileptogenic activity.

Management

In terms of treatment, no evidence-based guidelines exist to guide anticonvulsant therapy choices in elderly DS individuals. The study by De Simone et al. found that valproic acid and levetiracetam seem most efficacious in treating myoclonic jerks and generalized clonic-tonic seizures [73]. Other antiepileptic options exist and a treatment plan should be determined by an experienced neurologist.

Other considerations

It is important to emphasize the need for supervision and safety precautions in elderly adults with suspected seizures, as well as education of caregivers in terms of dealing with seizures when they occur. Activities that pose a risk for injury should be avoided. Swimming should be undertaken with great caution as an individual with a seizure disorder must be fully supervised. Depending upon the persons’ mobility and level of functional independence, individuals with seizures may require supervision when taking a bath or shower and during ambulation up and down stairs.

Extrapyramidal symptoms (EPS) are frequently associated with dementia in persons with DS. In one study 36% of elderly DS individuals who had dementia had EPS, while none of the nondemented patients showed any evidence of EPS [71]. Prior studies estimated that 20% of demented middle-aged to elderly DS patients displayed EPS [74]. Other studies have reported both lower percentages (9%) [75] and higher percentages (65%) [76]. Possible mechanistic links between dementia and EPS include premature aging of substantia nigra neurons and subsequent decline in dopamine production [77]. The contribution of basal ganglia calcifications in EPS has been examined, but these calcifications seem to be a near universal finding in adult individuals with DS [78,79], yet only a small percentage ever develop EPS.

Presentation

EPS often occurs late in the course of dementia, though occasionally is seen earlier. EPS does not accompany all cases of dementia, and when present it is usually of the rigid-hypokinetic variety [71]. Symptoms may include tremor, rigidity in the extremities, shuffling gait, masked facies, orofacial dyskinesia, bradykinesia, and frontal release signs. Resting tremors and myoclonic jerks were not notable components of EPS in the Vieregge study. From a caregiver’s management perspective, EPS may be more impairing than the cognitive aspects of dementia. Gait may be markedly affected, requiring close supervision and direction from caregivers. EPS also interferes with a person’s ability to perform activities of daily living that require fine motor (dressing, toileting, grasping, and holding utensils) and oral motor control (chewing, swallowing) placing additional burdens on caregivers.

Evaluation and management

EPS should be suspected if characteristic motor signs are seen, often in the setting of dementia and with or without seizures. Other conditions to be considered include the side effects of typical and atypical antipsychotic medications. Typically, EPS in the setting of dementia is poorly responsive to levodopa [74]. Case reports exist that have shown improvement on levodopa/carbidopa, leading to subsequent improvements in gait and ADLs. In one case, the patient was thought to have idiopathic Parkinson’s disease, while the other patient had dementia. Both patients had resting tremors and bilateral symptoms. Evaluation by a neurologist interested in movement disorders is warranted given the impact that EPS has on patient and caregiver quality of life.

Other considerations

It is important to emphasize the need for supervision and safety precautions in adults with significant EPS, as well as education of caregivers. Depending upon motor stability and level of function, individuals should be closely supervised when taking a bath, shower, making transfers on and off the toilet, or ambulating up and down stairs. Use of a cane or walker may be of benefit if used safely, a wheelchair may be necessary for safe transportation in the community. A soft, modified diet is recommended when chewing becomes difficult or coughing/choking is present indicating a high risk for aspiration.

Dysphagia appears to be more common in adults with DS, although it is not well studied in elderly individuals [80]. In the general population Alzheimer’s disease contributes to impairments in motor function and coordination during various phases of feeding, resulting in deterioration of the cough reflex and choking [81]. Beyond concerns for aspiration, swallowing dysfunction may also contribute to weight loss in elderly DS patients. It is likely that tooth loss and problems chewing also contribute to decreased oral intake.

Presentation

Dysphagia may be subtle, and patients will rarely report difficulties with eating. However, choking, gagging, or coughing during mealtime are all concerning symptoms and should be further evaluated. Some patients will merely avoid eating or appear to have a loss of appetite. Even when swallowing dysfunction is not apparent, silent aspiration may be occurring. Clinical indicators of aspiration in 70% of subjects from a young cohort of adults with DS suggest that they may be a high-risk group at an early age [82]. Thus high rates of pneumonia in adults with DS may very well be related to micro-aspiration during feeding and drinking [5,80]. About 13% of death certificates reviewed in New York in 2007 listed pneumonia due to aspiration or choking as the primary cause of death [83] and most bacterial pneumonias are likely linked to aspiration of pharyngeal contents.

Evaluation and management

Initial testing for swallow dysfunction in both symptomatic and asymptomatic individuals can be carried out with a simple 3 oz bedside water swallow test. A videofluoroscopic swallow study (VFSS) and referral to a speech- or feeding therapist for full evaluation should be considered when clinical suspicion is high. Gastroesophageal reflux may also result in symptoms of coughing, choking, and food avoidance and should always be considered. When aspiration is confirmed or strongly suspected, dietary modifications can be made. Persons with oral motor chewing difficulties and/or tooth loss without dysphagia may also require supervision at mealtime and modified food preparation.

Other considerations

While obesity is common in many adults with DS, older adults experience a decrease in BMI with advanced age compared to controls [84]. In a study of 201 adults with DS, only 13 (7%) were found to be underweight, all were over 50 years of age. Dysphagia can contribute to decreased oral intake, weight loss, choking, and respiratory infections which are a common cause of death for people with DS [85] Recurrent aspiration pneumonia may be part of a terminal downward cascade in aging people with DS. Feeding tubes have not been found beneficial in the general population with dementia and therefore are generally not recommended [86,87].

Dementia and decline

Treatment of dementia usually requires nonmedicinal approaches to supporting the individual, and medications to treat associated symptoms. Medications approved for the treatment of dementia in the general population have been found to have limited benefit. A Cochrane analysis found insufficient evidence of benefit for treating people with DS and AD with acetylcholinesterase inhibitors (AChEI) or the NMDA receptor antagonist, memantine [88]. An increase in behavioral symptoms was reported with donepezil. Eady et al. did report longer survival with those taking medications (donepezil) but the study group was younger and had other significant factors in their favor [89].

To improve sleep and normalize day-night sleeping cycle, exposure to light through a typical light-dark 24-h pattern can be beneficial [90]. Incontinence is common and assessing for urinary tract infections is important [91]. Gait dyspraxia can be an early symptom of dementia often leading to increased anxiety and fearfulness, which can impair functional ambulation prior to actual loss of walking ability [92].

Supporting the family

Supporting the family and other caregivers at the end-of-life is critical [93]. A change in the role of family caregivers is both physically and emotionally challenging and requires reprioritizing goals and a different philosophy of care. Signs of functional decline can be intermittent initially, but eventually accelerates which is frightening for families to manage. Family members have often focused on improving independence with daily needs and self-care, but as these skills erode, the entire family must adapt. Parents are often the primary caregiver and often elderly themselves. Siblings may need to provide care for both their sibling with DS and their aging parents. In the midst of rapid functional decline it often becomes clear that the parents are no longer able to manage the daily care of their son or daughter resulting in a need for skilled care support. As the individual and family face end-of-life, the dignity of the individual remains an important element of care [94]. Discussing contributing factors to maintaining the best quality of life is part of family support [94].

This may include discussion of:

• • A focus on doing what can still be done
• • Encouraging social engagement with friends and family, as tolerated
• • Physical activity, as tolerated
• • Healthy eating, nutritional supplementation is often required to maintain body weight
• • Entertainment, enjoyable music and movies

Advance directives

Discussion of advance directives for people with DS and their families has unique aspects. The discussion requires care to avoid eliminating a sense of hope or creating challenging obsessive symptoms. For family members, a clear discussion that this is a change in care not a removal of care. Because a sibling may be assisting both the person with DS and her aging parents with dementia and other health problems, situations arise in which the sibling is making multiple end-of-life decisions, for different family members. When such decisions occur in close proximity, additional emotional supports may be required.