Table 2.
Studies reporting association between sleep disturbances and clinical burden in AD patients
| Author | Relevant objectives assessed | Clinical outcome results |
| Bliwise, 1995 [19] | The impact of the severity of AD on behaviorally defined sleep disturbances | Greater functional impairment (ADL) was associated with moderately disturbed sleep; no significant correlation was observed between severe sleep disturbances and functional impairment (ADL). |
| Ownby, 2014 [58] | Subtypes of sleep disturbance in patients with AD, and the relation to patient characteristics | Both the moderate and severe sleep groups had worse cognitive function (MMSE), lower functional status (BDRC), and higher depression scores (CSDD) versus the normal sleep group. |
| McCurry, 1999 [47] | Frequency, predictors and impact of sleep problems in AD patients | Numerically greater memory (RMBPC) impairment, humanistic burden (BDRS) scores and depression (RMBPC) with increased frequency of sleep disturbances (defined by caregivers). |
| Prevalence OR: 1.6 for 3-point functional status (BDRS) score change in patients with sleep disturbance in past week. | ||
| Tractenberg, 2003 [4] | Efficacy of the Sleep Disorders Inventory (SDI) for assessing symptoms of sleep disturbance/disorder | No significant difference in functional impairment (ADL) for short sleep duration group versus≥6 h TST; 39.1 versus 42.9. |
| SDI scores were significantly associated with functional impairment (ADL) scores. | ||
| Tractenberg, 2005 [68] | Prevalence rates of sleep disturbance symptoms in those with possible AD, and a normal elderly control group, and the association of cognitive status with greater prevalence, worse symptomatology, or a different range of symptoms. | Greater functional impairment (ADL and IADL) for short sleep duration group versus > 6 h TST; 0.88 versus 2.60 and 1.9 versus 7.0, respectively. |
| Higher functional impairment (ADL) scores (less impairment) for sleep problems group versus no sleep problems; 3.5 versus 2.2. | ||
| No significant difference in functional impairment (IADL) for sleep problems group versus no sleep problems; 7.6 versus 6.6. | ||
| McCurry, 2006 [51] | Impact of higher % sleep on (caregivers’ reports of sleep disturbances in persons with AD and actigraph records of patients’ sleep-wake activity) on clinical outcomes. | Greater functioning (less functional impairment [IADL]) in those with higher % sleep |
| Less daytime sleepiness (ESS) in those with higher % sleep | ||
| Better QoL (QoL-AD) in those with higher % sleep | ||
| Better physical QoL (SF-36) in those with higher % sleep | ||
| Garcia-Alberca, 2013 [29] | The association between sleep disturbances and neuropsychiatric symptoms, cognitive and functional status of patients, and severity and duration of dementia | Worse functioning (B-ADL), worse cognition (MMSE, RAVLT-IR, RAVLT-DR and TMT-B), depression (NPI) and aberrant motor behavior (NPI) were associated with sleep disturbances |
| de Oliveira, 2014 [25] | Factors related to sleep satisfaction in AD patients | No correlation between cognition (MMSE and clock drawing test) and sleep satisfaction. |
| No difference in functional impairment (ADL or IADL) for unsatisfied sleep group versus satisfied sleep (4.97 versus 5.02 and 15.32 versus 13.97, respectively). | ||
| Greater behavioral disturbances (NPI total score) and higher dysphoria, anxiety and apathy scores (NPI) in patients with unsatisfied sleep versus satisfied sleep. Significance for a decrease of 0.079 h of sleep for each point increase in anxiety score and for an increase of 0.075 h sleep for each point increase in apathy scores. | ||
| No association between functional impairment (ADL) and sleep duration. | ||
| Ribeiro, 2018 [61] | Impact of sleep disorders, and manifestation in people with AD | Greater anxiety and depression (HADS) for sleep disturbances versus no sleep disturbances. |
| Yin, 2015 [70] | Five-year effect of nocturnal sleep disturbances on the long-term outcome in AD patients | No significant differences in cognition (MMSE) or functional impairment (ADL) for sleep disturbances versus no sleep disturbances groups at baseline. |
| Significantly worse cognition (MMSE) and functional impairment (ADCS-ADL) for sleep disturbances group versus no sleep disturbances after five years. | ||
| Significant increase in cumulative incidence of psychotic symptoms, eating problems and sundowning syndrome for sleep disturbances group versus no sleep disturbances after five years. | ||
| Leng, 2020 [44] | Sleep quality and health-related QoL in older adults with subjective cognitive decline, mild cognitive impairment, and AD | Total (SF-36), physical (PHCS SF-36), and mental (MHCS SF-36) QoL were associated with subjective sleep quality; moderate correlations between HRQoL and sleep quality. However, the AD group showed a weaker correlation than the other patient groups. Total and physical QoL were also moderately associated with sleep disturbances and total QoL alone was associated with sleep duration. |
| Zhou, 2019 [71] | Characteristics of sleep status and BPSD among AD patients in Eastern China, and the relationship among sleep disorder, behavioral and psychological symptoms of dementia, and cognition | Negative correlation between PSQI scores and cognition scores (MMSE) and functional impairment scores (ADCS-ADL). |
| PSQI was closely related to behavior/neuropsychological impairment scores (NPI total score) and depression and apathy scores (both NPI). | ||
| Lebrija, 2016 [41] | Sleep disorders and neuropsychiatric symptoms in Mexican patients with AD | Significant association between anxiety (NPI) and difficulty falling asleep (versus patients without difficulty to initiate sleep), waking up at night (versus patients not waking up at night to start the day) and early morning awakenings (versus patients without early morning awakening). |
| Significant association between aberrant motor behavior (NPI) and waking up at night (versus patients not waking up at night), wandering at night (versus patients not wandering at night), night awakenings (versus patients without night awakenings) and early morning awakenings (versus patients without early morning awakening). | ||
| Significant association between agitation (NPI) and waking up at night to start the day (versus patients not waking up at night to start the day). | ||
| Kabeshita, 2017 [37] | Sleep disturbances and other behavioral and psychological symptoms of dementia at different stages of AD | Behavior/neuropsychological impairment (NPI total score) was associated with sleep disturbances in patients with low CDR; no correlation in more severe AD |
| Chew, 2019 [23] | Sleep duration and progression of cognitive decline in subjects with mild cognitive impairment and mild AD | Longer sleep duration in patients with rapid cognitive decline (CDR) versus those without |
| Escudero, 2019 [28] | Association between neuropsychiatric symptoms and cognitive and functional decline in frontotemporal degeneration and AD | Sleep problems were predictive of cognitive decline after 2.5 years based on MoCA, but sleep problems at baseline were not associated with cognitive decline after 2.5 years based on MMSE. |
| The model on ΔLawton (functional impairment – Lawton scale) reached significant values showing that variability in ΔLawton was explained by the scores for depression and for sleep problems. | ||
| Mulin, 2011 [55] | Apathy and sleep/wake patterns in individuals with AD using ambulatory actigraphy | Greater WASO, time in bed, daytime inactivity periods and WASO normalized for time in bed in patients with apathy versus patients without apathy. |
| Moran, 2005 [54] | Sleep disturbance and its clinical correlates in a memory clinic population of AD patients | No significant difference in cognitive decline (MMSE, CAMCOG) and functional impairment (IADL, BDRS) between patients with and without sleep disturbances. |
| Significantly more aggressiveness (BEHAVE-AD) and worse behavioral disturbances (Global rating [BEHAVE-AD]) in patients with versus without sleep disturbances. | ||
| Leger, 2017 [43] | Impact of apathy or severity scores in patients with AD on TST at night | Negative correlation between TST and ADCS-ADL score, meaning TST was positively associated with functionally disability. |
| Increased TST (AES-I), decreased awakenings (AES-I), and increased sleep efficiency (AES-I) in patients with apathy versus patients without. | ||
| Shin, 2014 [63] | Impact of nighttime sleep on cognition and behavioral and psychological symptoms of dementia in AD | No significant correlation between PSQI total scores and cognition (MMSE [Korean version]) or functional impairment (B-ADL, SI-ADL) in AD group. |
| Apathy/indifference (NPI [Korean version]) significantly associated with PSQI total scores. | ||
| Sleep latency was negatively associated between and visuospatial functions and praxis; sleep efficiency was positively associated with praxis, K-BNT and RCFT; sleep duration influenced praxis. | ||
| After adjusting for age and education sleep latency was significantly associated with praxis, immediate recall and recognition, and sleep duration and efficiency correlated with praxis. |
AD, Alzheimer’s disease; ADCS-ADL, Alzheimer’s Disease Cooperative Study-Activities of Daily Living; ADL, Activities of Daily Living; AES-I, Informant-rated Apathy Evaluation Scale; B-ADL, Bayer Activities of Daily Living; Ba-ADL, The Barthel Activities of Daily Living Index; BDRS, Blessed Dementia Rating Scale; BEHAVE-AD, Behavioral Pathology in Alzheimer’s Disease; CAMCOG, Cambridge Examination for Mental Disorders of the Elderly; CDR, Clinical Dementia Rating; CSDD, Cornell Scale for Depression in Dementia; ESS, Epworth Sleepiness Scale; HADS, Hospital Anxiety and Depression Scale; IADL, Instrumental Activities of Daily Living; K-BNT, Korean version of the Boston Naming Test; MCI, mild cognitive impairment; MHCS, Mental Health Component Score; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; NPI, Neuropsychiatric Inventory; NR, not reported; PHCS, Physical Health Component Score; QoL, quality of life; QoL-AD, Quality of Life in Alzheimer’s Disease; RAVLT-IR, Rey Auditory Verbal Learning Test; RCFT, Rey-Osterrieth Complex Figure Test; RMBPC, Revised Memory and Behavior Problems Checklist; SI-ADL, Seoul-Instrumental Activities of Daily Living Scale; SNSB, Seoul Neuropsychological Screening Battery; STAI Y-1, State Trait Anxiety Inventory for Adults; TMT-B, Trail-making test; TST, total sleep time; WASO, wake after sleep onset.