Sleep and Cognition in Late-Life Depression

Depression commonly occurs with subjective as well as objective impairment in sleep and cognition.   However, few studies have examined the interaction between sleep impairment, cognition and depression in elderly cohorts.   Sleep disturbances predict increased risk for new onset depression and recurrence of depression in those with previous episodes.  Impaired sleep appears to reduce memory function and possibly reduce neurogenesis. 

Naismith and colleagues recently examined the correlations between sleep parameter and cognition in a group of 44 subjects with a lifetime history of depression (minimum age >45 years, mean 63 years) and a group of similarly aged adults without depression.  Neuropsychological testing in this study focused on domains felt to be impaired in mood disorders including: 1.) processing speed, 2.) attention, 3.)visual memory, 4.) verbal memory, 5.) language-as tested by counting number of animal names produced in one minute and 6.) executive function-planning, problem solving and response inhibition.

Sleep function was measured using actigraphy and sleep diaries.  Actigraphy typically involves using a wrist watch type device that measures movement during the night and provides an estimate of key sleep parameters including: 1.) total rest interval 2.) sleep latency—time from going to bed to falling asleep (in minutes), 3.) wake after sleep onset (WASO), 4.) arousals—number of periods during night where activity indicated being awake and 5.) sleep efficiency—the percent time asleep during the night

Elderly subjects with a history of depression (current depression ratings suggest a relatively mild depression cohort at time of study) showed increased WASO and decreased sleep efficiency (two highly correlated sleep variables).   WASO and sleep efficiency variables correlated with reduced cognitive function particularly in the domains of attention, memory (semantic and visual) and executive function.  Of note, late onset of depression tended to be associated with poorer sleep quality than earlier age of onset.  The authors controlled for depression severity in this study so the findings appear outside of this influence.

The authors suggest greater cognitive impairment in late onset depression may relate to white matter changes due to cerebrovascular disease.   White matter changes in frontal cortex-subcortical circuits have been associated with reduction in psychomotor speed and executive function.

The authors also note this study is unable to identify the sequencing and causal pathway for these relationships.  If impaired sleep directly impairs cognition, early identification of sleep abnormalities and treatment may limit associated cognitive impairment.  Sleep apnea also needs to be considered in this population, although the authors found no association between measures of sleep apnea and cognitive impairment.

The take home message from this study is that sleep impairment (poor efficiency) may be a marker for depression and cognitive impairment in those over 50.  Clinicians caring for the older adult, should carefully assess the health of the sleep of their patients and keep the sleep, cognition and depression triad in mind.  Sleep complaints in older adults need thorough assessment and should not be dismissed simply as age-related physiological in nature. 

Photo of Tiger Woods putting during practice for 2010 PGA championship courtesy of Yates Photography.

Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, Norrie L, & Hickie IB (2011). Sleep disturbance relates to neuropsychological functioning in late-life depression. Journal of affective disorders PMID: 21435728

Naps Boost Cognitive Performance in Seniors

Insomnia is a common complaint among elderly individuals. With aging, there is a pattern of decreased number of total sleep time and reduced time in deep sleep. Deep sleep is considered restorative sleep, an important component of feeling rested and alert the following day.


Sleep hygiene recommendations commonly warn against napping during the day time as it is felt to reduce the quantity and quality of sleep at night. However, many individuals report that napping during the day is helpful for them in getting sufficient sleep on a regular basis. Now there is some limited data that supports a role for regular napping for increasing total sleep time as well as some parameters of cognitive function.


Campbell and colleagues studied the effects of a month-long napping regimen in a series of individuals between the ages of 50 and 88 years of age. Key elements of the research design included:

• Inclusion criteria: age over 50 with self-reported good physical health, subjective insomnia complaints allowed but subjects had to score less than 5 on the Pittsburgh Sleep Quality Index and 2 or less on the sleep latency item from this scale, no regular sleeping medications, not taking psychotropic meds or other medications known to affect sleep, minor but not major medical problems, no periodic limb movements on baseline polysomnography
• Study variables/procedures: Sleep diaries and actigraphy at home 1 to 2 weeks before baseline laboratory examination, 3 consecutive nights and 2 days spent in sleep lab with polysomnography and neuropsychological testing including a test of logical reasoning, mathematical processing, letter memory search and reaction time test.
• Intervention: Randomization to either directed 45 minute nap or 2 hour nap, at least 5 times per week but recommended daily, to be completed in single setting before 6 pm to include daily sleep logs
• Outcome measures: Subjects returned for sleep lab evaluation for 2 nights at 2 and 4 weeks after randomization

The key elements of the outcome of the study:

• Napping did not change any of the night time sleep parameter: sleep onset latency, sleep efficiency or total nocturnal sleep time
• In 24 hour assessment of sleep both groups increased their total sleep time although as expected the long nap group had a longer total sleep time than the short nap group
• Neuropsychological performance improved in both groups at 2 and 4 weeks on three of the four neuropsychological measures (all but reaction time). The improvement was not statistically significant but the longer nap group tended to show greater improvement
• Adherence to recommended nap assignment: (9/11) in the short nap group met defined adherence while 5/10 in the long nap group met adherence—this difference was not significant

Although a small sample study, this research finding seems allay some concerns about a regular nap regimen for those over age 55 years of age. There does not appear to be evidence that napping impairs nocturnal sleep in duration or quality. The added sleep during the day with a nap in this study was accompanied by improvement in some elements of cognitive function. This improvement appeared to continue through 4 weeks and may not have reached its peak by that time. The authors note that none of the subjects were regular nappers before entering the study. 


So the take home message from the study is that for those 50 or older if you are taking a daily nap and feel it helps you, keep doing it. If you are not taking a daily nap and would like to consider adding one, it does not appear to be a risk for disrupting nocturnal sleep and you may get some cognitive boost from a daily napping regimen.


Photo of napping kittens courtesy of Wikepedia Commons author Tilman Piesk.


Campbell, S., Stanchina, M., Schlang, J., & Murphy, P. (2011). Effects of a Month-Long Napping Regimen in Older Individuals Journal of the American Geriatrics Society, 59 (2), 224-232 DOI: 10.1111/j.1532-5415.2010.03264.x

Low-dose Doxepin for Insomnia Treatment

Doxepin is a tricyclic antidepressant drug with significant sedative effect recently studied for use as a hypnotic in the treatment of insomnia.  Doxepin has strong antagonistic effects on several neurotransmitter receptors including the histamine (one and two), serotonin (two), alpha one adrenergic and muscarinic acetylcholinergic receptors.

Juliane Weber and colleagues recently reviewed clinical trial research related to doxepin and insomnia treatment.  For depression, doxepin typically requires 150 mg to 300 mg to achieve an antidepressant.  Many individuals are unable to tolerate this type of dose due to the sedative side effects.  Much lower doses (3 mg to 6 mg) have been investigated for effects on sleep.

A summary of the key points from their review:

• Doxepin decreased time awake after onset of sleep by 40-46%
• Total sleep time increased from 40 to 50 minutes per night
• Proportion of sleep time in REM and slow wave sleep did not change
• Elderly patients had similar effects with the lower 3 mg dosage
• Effects were similar for patients with chronic or transient insomnia
• In sleep lab testing doxepin reduced time to sleep onset from 35 minutes down to 20 minutes

A more recent study from Krystal and colleagues at Duke University looked at 1 mg and 3 mg doses of doxepin in elderly patients with chronic primary insomnia.  They found the 3 mg dose was effective in reducing wake time after sleep onset, total sleep time and overall sleep efficiency (percent of time asleep).

The duration of doxepin's effect has been studied for up to 12 weeks and there does not seem to be tolerance to the hypnotic effect over this duration.  At these low doses, doxepin appeared well-tolerated.  Longer term studies are needed to determine efficacy for periods of longer than 12 weeks.  One potential concern would be weight gain as the histamine and muscarinic receptors appear to be related to increased appetite and weight gain.

The FDA has approved doxepin 3 mg and 6 mg for insomnia treatment.  Typically, the lowest generic doses for this drug are 10 mg.  Three mg and 6 mg doses are available under the brand name Silenor.

This research suggests low-dose doxepin may be an alternative to hypnotics such as Ambien (zolpidem) for primary insomnia.  This research supports further study of current drugs for novel mechanisms and new indications.


Disclosure:  The author has no financial conflict of interest and has not received funding for research of this compound.

Image of chemical structure for two isomers of doxepin courtesy of Creative Commons authored by Ju.

Weber J, Siddiqui MA, Wagstaff AJ, & McCormack PL (2010). Low-dose doxepin: in the treatment of insomnia. CNS drugs, 24 (8), 713-20 PMID: 20658801

Krystal AD, Durrence HH, Scharf M, Jochelson P, Rogowski R, Ludington E, & Roth T (2010). Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week Sleep Laboratory and Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia. Sleep, 33 (11), 1553-61 PMID: 21102997