老年睡眠障礙 Sleep disorders in older people 財團法人彰化基督教醫院 精神科 廖以誠醫師

參考資料 Oxford Textbook of Old Age Psychiatry 2008,Robin Jacoby等人編著， 第673～686頁。 臨床老年精神醫學，黃正平編 ， 第157～162頁。

內容大綱 睡眠結構與老化的特徵 睡眠疾患之診斷分類 睡眠障礙之評估 常見老年睡眠疾患 Insomnia Sleep-related breathing disorders Circadian rhythms sleep disorders Excessive daytime sleepiness REM sleep behavior disorder Sleep-related movement disorders 其他（失智症、憂鬱症之睡眠障礙）

一般成人睡眠結構的特色（一） 一般REM latency 70-100 min. 1st REM 期間約 15分, 之後延長成20-40分 心跳與呼吸加速、肌肉鬆弛，作夢多 一個REM及Non-REM循環約90分 Stage3,4 主要出現在1st non-REM 期間 心跳與呼吸減緩，代謝降低，作夢少 人類體溫亦有日週期變化（約攝氏1度上下） 正午最高，午夜最低

一般成人睡眠結構的特色（二） 睡眠與清醒週期，主要由生理日鐘、環境刺激與一連串的大腦處理過程，共同維持 瞭解睡眠的二大原則 circadian clock 生理日鐘，下視丘之「上視交叉神經核」suprachiasmatic nuclei (SCN), 調節日光刺激與melatonin的分泌 瞭解睡眠的二大原則 Circadian 兩時段睡眠傾向：晚上，正午（the siesta time) Homeostatic stage 3,4 睡眠多寡、delta wave的強度與睡前的清醒時間長短有關（老年人較少）

Circadian Process of Sleep 睡覺與清醒的時間由一內在的生物時鐘所控制，呈約25小時的週期。 晝夜節律中樞位於下視丘的上視交叉神經核 (SCN)

Homeostatic Process of Sleep 睡眠的恆定作用取決於之前的睡眠量 之前睡得多  不嗜睡 之前醒著時間長  嗜睡 主要受下視丘睡眠中心調控 Ventrolateral Preoptic Area 失眠相關因素: ex. 遺傳 老化 疾病 白天的活動量與睡眠多寡

Polysomnography (PSG) 睡眠多項生理檢查 睡眠中同時紀錄多種生理訊號： 腦波圖(C3-A2,C4-A1,O1-A2,O2-A1) 眼動圖(LEOG,REOG) 下顎肌電圖(Chin) 腿部肌電圖(LEMG) 口鼻呼吸氣流(Airflow) 胸腹呼吸動作(THO,ABD) 心電圖(EKG) 血中含氧濃度 打鼾次數 睡覺的姿勢 以上訊號用來判斷睡眠分期及各項睡眠障礙

年輕成年人 老年人 1.一般REM latency 70-100 min. 1st REM duration 15min, 之後延長成20-40分 2.一個REM及Non-REM循環約90分 3.stage3,4 主要出現在1st non-REM period 4.REM主要出現在睡眠末期（1/3）

老年人之睡眠變化 Reduced total sleep time Overall decrease in sleep efficiency sleep efficiency 由90％降至70％, bedtime > sleep time Changes of sleep architecture stage 1,2 增加，stage 3,4 減少 Slow wave sleep 量減少，振幅也降低 Less REM sleep, REM latency 變短，1st REM 期間變長 sleep latency 變長（＞30分），入睡較難 More night-time arousals & recalled awakenings Phase-advanced rhythm（早睡早起） More daytime napping 白天瞌睡增加 主因夜間睡眠片段化（與睡眠時間長短無關） 次數太多、時間太長且慢性化，需注意是病態 Multiple sleep latency test (MSLT), 測試5 naps (10am,12noon,2pm,4pm,6pm)的sleep latency, 一般成人至少需15分，正常老年人需8-12分，若少於5分，則為病態 。 晚上入睡困難女性較多 有報告REM所佔比例降低

睡眠障礙診斷分類 (1) International Classification of Sleep Disorders (ICSD) 國際睡眠障礙分類 Insomnia Sleep-related breathing disorders Hypersomnia Circadian rhythms sleep disoeder Parasomnia Sleep-related movement disorder

睡眠障礙診斷分類 (2) DSM-IV-TR 精神疾病診斷和統計手冊 第四版 Primary sleep disorders Dyssomnias Primary insomnia Primary hypersomnia Narcolepsy Breathing-related sleep disorders Circadian rhythm sleep disorders Dyssomnia NOS: Restless legs syndrome ( RLS ), Periodic limb movements ( PLM ) Parasomnias Nightmare Sleep terror Sleepwalking Parasomnia NOS: REM sleep behavior disorder Sleep paralysis 不分insomnia or hypersomnia 而以intrinsic or extrinsic 取代

睡眠障礙診斷分類 (DSM-IV-TR) - 2 Sleep disorders related to another mental disorder Insomnia related to …… Hypersomnia related to ….. Other sleep disorders Sleep disorder due to general medical condition Substance-induced sleep disorder EDS最常見的原因： 1. Sleep apnea 2. Narcolepy (老人較少見） 3. PLM ＆ RLS

睡眠障礙診斷分類 (ICD-9-CM) ICD-9-CM (不詳列） － Specific disorders of sleep of nonorganic origin (307.4) － Cataplexy & nacrolepsy (347) － Sleep disturbances (780.5) EDS最常見的原因： 1. Sleep apnea 2. Narcolepy (老人較少見） 3. PLM ＆ RLS

睡眠障礙評估(1) 完整的睡眠史評估，包括個案與同床伴侶 個案常見主訴： 同床伴侶常見主訴： 入睡困難 維持睡眠困難 早醒 睡不飽，精神不好合併白天嗜睡 同床伴侶常見主訴： Snoring, Breath pauses, Odd behavior Fidgety & abnormal movements

睡眠障礙評估(2) 完整的睡眠史評估，包括個案與同床伴侶 Main complaints Extent of the problem Any risk like fall asleep whilst driving Extent of the problem Onset, chronology, duration, frequency, progression, reasons to address the problem now, impact on daily living, response to previous treatment Psychiatric and medical co-morbidity Current prescribed and over-the-counter medication

睡眠障礙評估(3) 完整的睡眠史評估，包括個案與同床伴侶 Current and past sleep habits Pre-bed activities, bedtime, sleep duration, waking up time, getting up time, number of sleep disruption, and toilet habits during the night Sleep environment: Noise, temperature, personal stressors, sleep problems of the bedpartner Daytime habits: Amount of physical exercise, number and duration of daytime naps, exposure to light, smoking, alcohol, caffeine

失 眠 Insomnia (1) Insomnia 是老年人最常見的睡眠抱怨，常沒有被診斷，而影響個案的生活品質，導致個案生病、機構化與跌倒。 失眠包括： 入睡困難、維持睡眠困難、主訴睡不飽(non-restorative sleep) 臨床定義 失眠症狀持續超過2週，伴隨隔日白天功能受損 盛行率 依照病人族群與診斷標準而異 一般成人30-35%, 老年30-60%（女性較多）

失 眠 Insomnia (2) Transient insomnia （2週） Intermediate insomnia （2-4週） Chronic insomnia （>4週） Pathogenesis of insomnia 前置因素（Predisposing Factor） 個人特質: age, gender, weak sleep drive and hyperarousal 觸發因素（Precipitating Factor） 開始發生的事件: pain, stress, medical conditions, physical illness, and a noisy environment. 持續因素（Perpetuating Factor） 讓失眠長時間維持下去的因素: dysfunctional thoughts （如excessive worrying about the consequences of poor sleep） Primary (idiopathic) insomnia, unrelated to any illness exists, but is rare in elderly patients

失 眠 Insomnia (3) Insomnia related to other conditions Psychiatric disorders Depression, mania, anxiety disorders (OCD, PTSD, and panic disorders) Insomnia can precede and contribute the onset of depressive episode. Chronic insomnia at risk of using alcohol Alcohol 降低sleep latency，但是導致sleep fragmentation, REM sleep suppression, and early morning awakening. Other sleep disorders Sleep-related breathing disorder, PLMD, RLS 等 Physical conditions Chronic pain, chronic pulmonary disease, congestive heart failure, chronic renal disease, DM, hyperthyroidism Medications CNS stimulants: dexamphetamine, methyphenidate, SSRIs, bronchodilators, theophylline, corticosteroid, decongestants

失 眠 Insomnia (4) Assessment Subjective complaints of the degree of insomnia are often greater the objective measurements of insomnia in PSG studies or questionnaires Detail sleep history taking Sleep diaries Actigraphy Thorough physical examinations Mental state examinations Routine blood test, include thyroid function testing

失 眠 Insomnia (5) Treatment 確認並處理underlying causes 相關疾病好轉，失眠隨之改善 沒有找出內在病因，不適當的治療會使症狀惡化 OSA 使用sedative hypnotics 治療，sleep fragmentation惡化 不論內在病因為何，Good sleep habits & sleep hygiene & realistic goals & expectations 都需被強化 Hide clocks in bedroom, but an alarm should be set. Non-pharmacological treatment Cognitive behavioral therapy Cognitive therapy Educations with sleep hygiene Stimulus control therapy* Sleep restriction therapy* Relaxation therapy Cochrane Review 2003: CBT對60歲以上老年人sleep problem有中等程度療效，尤其sleep maintenance insomnia

失 眠 Insomnia (6) Treatment Pharmacological treatment 藥物選擇包括： Benzodiazepine, non-benzodiazepine, sedative antidepressants, and melatonin agonists Sedative hypnotics Glass et al.,2005. meta-analysis: 短期療效：↑sleep time, ↓night-time awakening 副作用：認知功能受影響，跌倒，白天疲勞等 Risks may outweigh the benefit, esp. chronic insomnia 需注意老年個案 polypharmacy, co-morbidity Hypnotics 使身體症狀惡化, rebound insomnia, 產生tolerance, withdrawal symptoms（短效BZD較常見，建議逐漸減量） Hypnotics 最好使用在「診斷確認案例」，短期2～4週需要時使用，選用最低有效劑量。

失 眠 Insomnia (7) Treatment Sivertsen et al., 2006 Morin et al., 1999 CBT is superior to zopiclone in the short-(6 weeks) and long-(6 months) term management of chronic insomnia in the elderly. Morin et al., 1999 All patients who received CBT had longer-lasting effects compared with temazepam Current evident suggest CBT may be the first-line treatment, especially for chronic insomnia in patients without severe motor disability and cognitive impairment.

Sleep-related breathing disorders -1 Partial or complete respiratory impairment during sleep middle-aged and elderly patients 主要由obstruction of the upper airway/oropharynx. Obstructive Sleep Apnea (OSA) 60歲以上約20%，男性多。 Mixed causes for sleep apnea are frequently in elderly with neurodegenerative disorders, such as PD & DLB Correct and early diagnosis of sleep apnea Treatable conditions Untreated OSA with high mortality & morbidity Severe OSA also a risk factor for an ischemic stroke in elderly patients (aged 70-100) Undiagnosed OSA at risk of using alcohol or BZD, vicious cycle

Sleep-related breathing disorders -2 Assessment Bedpartners 常是提供重要病史，及要求個案門診檢查的重要關鍵 OSA的典型症狀 Loud snoring, evident breathing pauses, daytime sleepiness 需要與depression 鑑別診斷 PSG (portable PSG) AHI (apneas / hypopneas index ) : 5-15 mild, 15-30 moderate, >30 severe OSA Multiple sleep latency test (MSLT) Sleep latency > 10min 正常, < 5 min 不正常 Maintenance of wakefulness (MWT) 維持2小時的清醒 主要是測量治療效果

Sleep-related breathing disorders -3 Treatment Treatment of OSA Weight reduction Restriction of alcohol at bedtime Abstinence from sedatives Continuous positive airway pressure (CPAP) First choice of symptomatic treatment Oral appliance Uvulopalatopharyngoplasty (UPPP) Persistent daytime sleepiness despite the treatment with CPAP may benefit from treatment with modafinil

Circadian rhythms sleep disorders -1 Four main type Advanced sleep phase syndrome 老年人最常見 Falling asleep several hours before conventional norms. Delayed sleep phase syndrome Non 24-hours sleep-wake syndrome Irregular sleep-wake pattern Prevalence rate unknown Primary intrinsic pacemaker of circadian rhythms is suprachiasmatic nuclus. Tends to advance with ageing

Circadian rhythms sleep disorders -2 Assessment Sleep history, sleep diaries (至少紀錄2週) Actigraphy 排除depression or chronic insomnia Treatment Advanced sleep phase syndrome Bright light therapy 晚上9-11點（7-9點）間，2500 lux 的強光照射2小時, 若10,000 lux則 30-45分 Chronotherapy High motivation Further advance the sleep times, 2 days for 3 hours

Excessive daytime sleepiness -1 老年人較少原發性 Narcolepsy, idiopathic hypersomnia, recurrent hypersomnia 較多次發於 Disturbed sleep, neurodegenerative disorders (AD & PD), and depression, medications Prevalence rate in older adults is 15-20% Assessment Sleep history, sleep diaries, Epworth sleepiness scale PSG + MSLT MWT for 評估治療效果 Treatment 治療內在病因 Alerting agents: 目前對老年次發型excessive daytime sleepiness效果證據不足 Modafinil, dextroamphetamine, methylphenidate

REM sleep behavior disorder -1 Lack of muscle atonia during REM sleep with dream-enactment behavior. Then risk of injury. Usually manifests above the age of 50. 社區prevalence rate 0.5-0.8%, 男性較多. 15-34% RBD in PD Assessment Bedpartner’s history of acting out dreams, and injury during night. PSG confirm lack of muscle atonia in REM sleep Treatment First-line clonazepam 0.25-0.5mg /night 長期使用需注意副作用 其他如melatonin 3-12mg 睡前

Sleep-related movement disorder -1 Restless leg syndrome ( RLS ) Urge to move the legs, 併有uncomfortable and unpleasant sensation in the legs. 休息不動時出現，動一動會好轉 晚上、入睡前惡化 Assessment Purely on history, 不需要PSG 80% with periodic limb movements Iron deficiency, check ferritin (below 50ug/dl) Treatment Dopaminergic agents: levodopa Dopamine agonist: ropinirole, pramipexole Gabapentin and carbamazepine Iron substitution for iron deficiency

Sleep disorder with depression 憂鬱症之睡眠型態改變 入睡困難 REM latency縮短（乃depression 的癒後指標，對藥物反應較好） 過多REM（睡眠初期） 睡眠效率降低 睡眠片斷 早醒性失眠 與睡眠老化很難區分，尤其早醒 晚發型老年憂鬱症較早發型較少有睡眠障礙 有效治療後，睡眠型態可恢復正常 Shortened REM latency 乃depression 的癒後指標 與睡眠老化很難區分，尤其早醒 REM sleep 分成tonic and phasic components Tonic activity: low-voltage EEG, muscle tone decrease phasic activiy: eye movement bursts, dream, 增加則REM density增加

失智症與睡眠障礙 -1 AD患者夜間睡眠特徵： 睡眠片段化、夜間驚醒次數增加， 第3、4期睡眠與REM睡眠減少 第1期睡眠增加。 睡眠效率下降 抱怨疲倦及白天睡覺增多 下午3點出現精神混亂、行為激躁不安（日落症候群 sundown syndrome），導致照顧者壓力大，不得已將病患被送至安養院

失智症與睡眠障礙 -2 睡眠週期混亂 失智症合併憂鬱的老年人 合併睡眠呼吸終止患者 大腦約日節律退化 外在環境誘因減少（尤其機構中老人）：日夜作息變化不大，社交與身體活動變少，長期臥床，少暴露於日光下。 嚴重者，白天無法持續清醒超過1小時，夜間無法持續睡上1小時以上。 失智症合併憂鬱的老年人 其睡眠變化比單純失智症更嚴重 合併睡眠呼吸終止患者 認知功能更差

失智症與睡眠障礙 -3 非藥物治療優先 藥物治療 認知行為治療 使用光照治療 有安眠作用的抗憂鬱劑與抗精神病藥物比安眠藥物好 但是失智症老年人常無法配合，需要照顧者從旁協助。 使用光照治療 傍晚到晚上 2500 lux 的強光照射2小時，最好是太陽光，一般室內燈光無效，室內需用light box. 藥物治療 有安眠作用的抗憂鬱劑與抗精神病藥物比安眠藥物好

結 語 張書森、李明濱: 台灣醫學2003年7卷4期，608頁

老年期物質使用疾患 Alcohol and substance abuse in older people 財團法人彰化基督教醫院 精神科 廖以誠醫師

參考資料 Oxford Textbook of Old Age Psychiatry 2008,Robin Jacoby等人編著， 第641～661頁。

Introduction Alcohol use disorders (AUDs) Medication use disorders (MUDs) 老年人較常使用藥物，因此有較高的機會發生MUDs Illicit drug use 現階段老年人少見，將來可能越來越多 與年輕人比較，臨床特徵非典型，且容易被其他病症掩飾而沒有被發現，更沒有治療

AUDs: definitions & diagnosis AUDs: a general term, spectrum of problems associated with alcohol use. From excessive consumption of alcohol above recommended ‘safe’ or ‘healthy’ level of intake, to harmful use and alcohol dependence. Five main alcohol categories Abstinent Moderate drinkers Heavy use: drink above recommended level, without obvious negative social, behavioral of health consequences Alcohol use is problematic but milder in severity than dependence. ‘binge drinkers’ Alcohol dependence DSM-IV or ICD-10 no elderly specific criteria for AUDs

AUDs: epidemiology -1 Under-estimated

AUDs: epidemiology -2 隨著年齡增加，AUDs的盛行率下降 AUDs盛行率受以下因素影響 Premature deaths of early-onset AUDs AUDs盛行率受以下因素影響 認定個案的診斷嚴謹度不同 Excessive alcohol consumption VS alcohol dependence 研究地點 社區：2-4% alcohol misuse or dependence 住院：急診14%, 護理之家18%, 精神科病房 23% 疾病種類 2/3 early-onset AUDs, 1/3 late-onset AUDs Early-onset AUDs 有較多家族史，反社會人格，症狀較嚴重，且造成身體疾病傷害

AUDs: aetiology, risk factors Complex interactions between several factors Biological/medical factors Positive family history Genetic risk AUDs與生理、精神疾病互動影響 Age-related physiological change Social factors Male gender, risk factor 世代、文化變遷 Psychological factors Personality types & traits Early onset AUDs: antisocial personality, hyperactivity, impulsivity Late onset AUDs: neuroticism & depression

AUDs: clinical features, comorbidity -1 Physical aspects

AUDs: clinical features, comorbidity -2 Neuropsychiatric & socio-demographic aspects

AUDs: clinical features, comorbidity -3 AUDs VS dementia

AUDs: 臨床評估、檢查與篩檢 Clinical assessment Investigations Screening Subtle and atypical nature of AUDs in the elderly 較低的飲酒量，也可能導致老年人身心損傷與造成問題後果 其他側面訊息與評估 Investigations 依照臨床評估後，安排相關的檢查 包括Lab. CT/MRI, endoscope 等 Screening CAGE, AUDIT-5 等 Detect at-risk, not diagnostic tool 不建議大量篩檢用，耗費成本 但建議對high-risk 族群，進行篩檢

AUDs: management & prevention Primary prevention 1/3 older people with AUDs 是在老年期才發病。因此是可以事先預防的。 其他與一般成人之酒藥癮防制策略一樣。 Secondary prevention ‘at risk’ drinking behaviors Brief psychological interventions in primary care Tertiary prevention Treatment existing AUDs Biological/medical treatment Detoxification, 老年人注意withdrawal symptoms明顯，因合併有其他內科疾病， parenteral or oral thiamine 避免Wernicke-Korsakoff syndrome Social treatment 解決經濟問題，工作，居住等問題 Psychological treatment Motivational interviewing, addiction counselling

AUDs: prognosis Late onset AUDs better prognosis than early onset or life-long AUDs May related to shorter history and milder severity of AUDs, higher income level, more intact social support. 至於 early onset and life-long AUDs, 有較嚴重的身體、精神疾患，反社會人格及認知功能損傷，導致其治療困難，預後較差。 老年人AUDs 若併有「認知功能障礙」 認知功能退化，會影響相關治療，

Medication use disorders in older people -1 Older people use more medications and are at a higher risk of medication use disorders (MUDs) than any other age group (Chutka et al., 2004). High levels of prescribing of both psychotropic and non-psychotropic medications for older people, which may at times be inappropriate, along with variable compliance, altered pharmacokinetics, reduced functional ability, and increased levels of physical, psychiatric, and cognitive morbidity means that older people are at higher risk of developing MUDs than any other age group.

Medication use disorders in older people -2 Clinical features of MUDs may be atypical and masked by other conditions and thus go undetected and untreated (Beers et al., 2000). As with AUDs, elderly specific criteria are not cited, but the same general principles apply; older people are likely to experience harm at lower levels of use and clinical features guiding diagnosis are more likely to be atypical and masked by other health problems. Medications may be divided into prescription-only (generally more potentially toxic) and ‘over the counter’ (OTC) medications. significant problems with abuse of common OTC medications such as paracetamol or cough mixtures containing codeine. divide medications into psychotropic (abuse associated more with neuropsychiatric effects) and non-psychotropic.

Medication use disorders in older people -3 MUDs may be conceptualized as arising from over-use, under-use, or inappropriate use of medications (Beers et al., 2000). Over-use occurs when a drug is used when no drug should be used at all. Drug misuse occurs when the wrong drug is used or a drug is used at the wrong dose, at the wrong schedule, or for the wrong duration. Under-use occurs when a drug is not used, although it is indicated. MUDs may be further complicated due to interactions with alcohol (taken only at moderate levels or in the context of an AUD) or with illegal drugs. For example, an older person on anticoagulant treatment may be unknowingly doing themselves harm, even if their alcohol intake is moderate.

Illicit drug use in older people Illicit drug use in older people is far less of a problem in comparison to MUDs and so will receive less attention. There is emerging evidence that, as with AUD, generations of people reaching old age in the coming decades may carry with them higher levels of illicit drug use than current and past generations of older people (Patterson and Jeste, 1999). Principles similar to those seen with AUDs and MUDs apply, in that lower levels of drug intake are required to cause harm and presentation may be atypical and thus go undetected.

Smoking in older people -1 Significant proportions of older people (approximately 10%) smoke (Bratzler et al., 2002), and this figure is likely to be higher again for older people with psychiatric disorders such as depression (Covey et at., 1998). The health impact of smoking is well documented elsewhere and includes malignancies (lung, oesophageal,bladder etc.), cardiovascular disease (ischaemic heart disease, cerebrovascular disease, peripheral vascualr disease, etc.), respiratory disease (chronic obstructive airways disease), and countless other problems. The effects of smoking are cumulative and age-related and it has been estimated that 70%of the excess mortality attributed to smoking in the USA occurs in those over the age of 60 (Burns , 2000).

Smoking in older people -2 The key message from recent research on smoking in older people is that smoking cessation is possible in this age group and is worthy of active consideration in the individual clinical setting and in a wider public-health context, in view of the considerable health benefits that are likely to accrue. LaCroix and Omenn (1992) found that older smokers who quit have a reduced risk of death compared with current smokers who quit have a reduced risk of death compared with current smokers within 1-2 years of quitting and overall risk years of death approaches that of those who never smoked after 15-20 years of abstinence. Although the benefits of smoking cessation for longevity are most pronounced in younger people , a large study of smoking cessation has demonstrated that men over the age of 65 gained 1.4-2.0 years of life and women gained 2.7-3.7 years (Taylor et al.,2002).