The Effects of Electroconvulsive Therapy on Neurocognitive Function in Elderly Adults

Electroconvulsive therapy (ECT) is a commonly used treatment for elderly adults with severe major depressive disorder. Technical advances have maximized the efficacy of ECT while reducing side effects, particularly cognitive adverse effects. Careful monitoring of depressive symptomatology and neurocognitive functions using measurement-based care methods are recommended during the treatment course to systematically guide the administration of ECT. In this systematic review, the authors describe the advances in ECT administration that have improved its efficacy and summarize the available information regarding the associated adverse cognitive effects in elderly adults.
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Major depressive disorder (MDD) is a chronic and debilitating disease that results in significant functional impairment in elderly adults.^1,2 The reported prevalence of depression is high in elderly patients, and studies have indicated that it is associated with increased age and poor health.^3,4 Depressive episodes tend to be lengthier in elderly adults as compared with younger persons, and common depressive symptoms include gastrointestinal symptoms and middle and late insomnia.⁵ Consequently, late-life depression contributes to poor quality of life, impaired cognitive abilities, and an increased health burden and mortality risk.^6,7

Antidepressant strategies for late-life depression include pharmacotherapy, psychotherapy, or a combination of both. Although psychotropic medications may be beneficial, many geriatric patients are commonly taking other medications for medical illnesses, increasing the risk of complications from drug—drug interactions and intolerability from medication side effects. Furthermore, some geriatric patients may not benefit from pharmacotherapy or psychotherapy. These patients are considered to have treatment-resistant depression, and electroconvulsive therapy (ECT) is recommended in such cases.^8,9

ECT is an accepted acute, continuation, and maintenance treatment for geriatric patients with MDD, particularly those who present with psychotic symptoms, acute suicidal ideation and threat, or treatment-resistant depression.^10-12 Technical advances have maximized the ECT efficacy to side-effect ratio, particularly with regard to the reduction of cognitive side effects.^13-16 Currently, ECT is the only neurotherapeutic intervention recommended for routine clinical use by the American Psychiatric Association.¹⁷

In this systematic review, we describe the advances in ECT administration that have improved its efficacy and summarize the available information regarding the associated adverse cognitive effects in elderly adults. To carry out the systematic literature review, independent searches in the PsycINFO (from 1806 to 2010) and MEDLINE (from 1947 to 2010) databases were performed using the following terms: electroconvulsive therapy, ECT, cognition, neurocognition, neurocognitive, cognitive impairment, memory, elderly, and geriatric. To control for duplicate information, the search results were imported into and managed with EndNote (version X3 for Macintosh, Thomson Reuters, Carlsbad, CA). In this review, we included only articles written in English that mentioned the terms ECT, geriatric, and neurocognitive (or an aforementioned variant) in the abstract, which yielded a total of 17 articles.

Advances in the Administration of ECT

Several improvements in ECT practices, including modifications in ECT stimulus waveform, stimulus dosing,¹⁸ and electrode configuration,¹⁹ have helped to maximize the efficacy of this treatment while minimizing its adverse neurocognitive effects. Initially, ECT was delivered via sine waves; however, due to the poor cognitive side-effect profile observed with this waveform, ECT devices are no longer manufactured to produce sine wave currents.²⁰ The new generation of devices employ a brief pulse waveform (0.31-0.5 pulse width),²¹ with the most recent devices providing an ultra-brief pulse waveform (≤0.3 pulse width). The brief and ultra-brief pulse waveforms are efficacious and result in fewer cognitive side effects compared with sine wave currents²¹; however, one study revealed that these waveforms may be ineffective when bitemporal electrode placement is used.²²

Stimulus dosing evolved over the decades as research showed that ECT could be enhanced when administered at specified magnitudes above the seizure threshold.^23-25 A patient’s seizure threshold, which is the amount of energy (ie, stimulus dose) needed to elicit a tonic-clonic therapeutic seizure, is determined during the first ECT treatment. On subsequent ECT sessions, the amount of energy used to elicit the therapeutic seizure is increased using one of three predefined methods. The need to increase the amount of energy to elicit a seizure was based on a study that found that the seizure threshold increases during the ECT course; this is a biologic phenomenon that is similar to the habituation observed with medication effects.^26,27 The three methods that are used in clinical practice to determine subsequent energy dosage levels include the age method, half-age method, and empirical titration method.^28-30 When using either age-based method, younger patients are treated with lower doses, whereas elderly patients are treated with higher doses. While age-based approaches are useful dosing strategies, they do not take individual variability into account.²⁹ In contrast, the empirical titration method is individualized and involves stepwise administration of ECT stimuli from low to high doses until a tonic-clonic seizure is obtained on the first treatment.²⁴ Subsequent ECT treatments are administered at higher dosages than the first ECT treatment.

The three standard ECT electrode placement configurations routinely used in clinical practice are bitemporal, right unilateral, and bifrontal (Figure). Bitemporal placement involves applying the two ECT electrodes on each of the temporal lobes. This configuration has been suggested to have a more rapid response rate³¹; however, it also has been found in many investigations to have a poor cognitive side-effect profile relative to the other configurations.^16,22 Right unilateral placement involves applying one electrode on the right side of the vertex on the scalp and the other electrode on the right temporal lobe. This configuration is thought to spare the left temporal lobe from direct electrical stimulation, thereby minimizing neurocognitive sequelae.^21,23 Bifrontal placement involves applying the electrodes to the right and left frontal cortices. This placement is hypothesized to allow the rapid response of the bitemporal placement, while maintaining the minimal cognitive side-effect profile of the right unilateral electrode configuration. This placement strategy was developed in an effort to spare both temporal lobes from the full ECT stimulus.^32-35 All three electrode configurations continue to be investigated to determine their optimal use.  

Efficacy of ECT

Research has continually found ECT to have exceptional efficacy in the acute phase of treatment, with remission rates as high as 80%.^36-38 One of the key benefits of ECT is that it produces a rapid onset of response (≥50% decrease in symptom severity) and remission.³⁹ For example, of the first 253 patients enrolled in the Consortium for Research in ECT (CORE) trial, 54% achieved response by the third ECT treatment, and 83% by the sixth ECT treatment.⁴⁰ Regarding remission, 65% of the sample achieved remission by the tenth ECT treatment, and the rate of remission increased from 10% to 60% between the fourth and ninth ECT treatments.40 This study shows that ECT is beneficial to patients who are in critical condition due to severe psychiatric illness, providing rapid response and remission.

A constraint to the effectiveness of ECT is the high relapse rate following the completion of the acute ECT course.⁴¹ Research has found that the relapse rate can be as high as 84% when no additional treatments are provided, 60% when monotherapy with nortriptyline is provided, and 39% when combined pharmacotherapy with nortriptyline plus lithium is provided.⁴² In the CORE trial, the relapse rate for patients receiving continuation ECT or combined pharmacotherapy with nortriptyline plus lithium was 37.1% and 31.6%, respectively, a difference that was not statistically or clinically significant.³⁶ A recent review suggests that evidence-based psychotherapy may be a useful augmentation strategy with ECT during the continuation phase of treatment.⁴³

ECT-Associated Neurocognitive Adverse Effects

The neurocognitive side effects associated with ECT have been an area of interest for researchers and clinicians since the first treatments were administered decades ago, and many studies have assessed the neurocognitive effects of this treatment, taking into consideration the severity of psychiatric illness and various cognitive domains, with a central focus on memory functions. Impairment in cognitive performance has been differentially associated with severity of depression.⁴⁴ Cognitive slowing is common in elderly patients with depression, and this is a factor that researchers must consider when reviewing the effects of ECT on neurocognitive performance in these patients. In addition, several cognitive deficits are often associated with late-life depression, including decreased processing speed, poor verbal memory, executive dysfunction, and decreased concentration. Some investigations have reported improvements in memory function, attention, and learning after ECT treatment^45,46; however, it is still unclear whether these findings resulted from decreased depressive symptomatology, improvements related to the treatment itself, or a combination of these factors.

Acute Neurocognitive Effects

As demonstrated in many studies, ECT can produce acute cognitive adverse effects, including disorientation (eg, forgetting name, age), which can last up to 60 minutes after each treatment; amnesia for newly learned information (anterograde), which can last up to 1 month after the acute ECT course; amnesia of previously learned information (retrograde), which can last up to 6 months after the acute ECT course for autobiographic information; and decreased processing speed, which can occur both during and after the ECT session (Table). In a study by Pettinati and Bonne⁴⁷ of cognitive functioning in patients with depression, individuals 65 years or older (mean age, 69.7 years; standard deviation [SD], 3.76) who had undergone at least one prior ECT treatment took significantly longer to complete the Trail Making Test (Part B), a measure of attention and cognitive flexibility, than did older patients with no history of ECT and younger patients with depression (mean age, 41.7 years; SD, 12.45) regardless of their ECT history, requiring 326.99 seconds to complete the test compared with 109.39 seconds for younger patients with a history of ECT and 64.46 seconds for elderly patients with no history of ECT.⁴⁷ While these findings provide evidence that both age and treatment history with ECT can contribute to decreased attention, processing speed, and cognitive flexibility, cautious interpretation is warranted as the results could have been confounded by the participants’ education level and the presence of psychomotor retardation, which can also impact test performance.  

While a link has been suggested between increasing age and the probability of symptom improvement due to a more rapid therapeutic response with ECT, older age is also associated with an increased risk of cognitive side effects. Age has consistently been linked with greater severity of postictal confusion and medical risks such as cardiovascular complications after ECT. Disorientation and confusion are common side effects that occur immediately after ECT and can take up to 60 minutes to resolve. Fraser and Glass⁴⁸ analyzed postictal confusion and disorientation in a sample of older adults (mean age, 73 years; SD, 6) undergoing ECT and compared time to reorientation after bitemporal and right unilateral electrode configuration. The authors found that participants who underwent ECT with bitemporal electrode configuration took significantly longer to achieve reorientation and experienced more confusion and delirium compared with patients who received ECT using the right unilateral electrode configuration. A study by Nelson and Rosenberg⁴⁹ that assessed ECT in elderly patients with dementia found transitory increased confusion in some patients following treatment; the authors noted a correlation between preexisting dementia and occurrence and severity of postictal disorientation.

The notion that ECT results in cognitive adverse effects has been disputed in certain clinical studies.^45,46,50,51 Because depression in geriatric patients is highly resistant to treatment, ECT is a frequently used intervention and often proves more successful than other antidepressant methods. Researchers have observed improved global cognitive functioning in many patients,^45,52 as illustrated by better performance on the Mini-Mental State Examination (MMSE)⁵³ and decreases in Montgomery-Asberg Depression Rating Scale (MADRS)⁵⁴ total scores. A study of 78 patients between the ages of 18 and 88 years who had depression with melancholic or psychotic features and were treated with ECT found a significant positive correlation between age and response to ECT, as demonstrated by mean improvement in MMSE and MADRS scores.⁴⁵ Study participants between the ages of 75 and 88 years had a mean improvement in MADRS scores of 29.50 and an average increase in MMSE scores of 4.42. Furthermore, a study of ECT by O’Connor and associates⁸ that included 253 patients with MDD who were between 18 and 85 years of age reported that participants in the older age group (≥65 years) showed better efficacy rates compared with the younger cohort. Specifically, of the individuals who completed the study protocol, 90% of the participants age 65 years and older showed a positive response compared with 70% of participants age 18 to 45 years. Tew and colleagues⁵⁵ conveyed comparable findings in a large cohort (n = 286) of patients with MDD who received ECT. In this study, 73% of participants between the ages of 60 and 74 years and 67% of participants 75 years and older responded to ECT compared with 54% of participants under the age of 60 years.

In addition, a study that assessed the effects of ECT in patients with severe depression in four distinct age groups found a significant correlation between age and response to ECT.⁴⁵ Specifically, the mean improvement in total scores on the MADRS was greatest for patients between 75 and 88 years of age, and a 72% response rate was reported for patients over the age of 62 years versus a response rate of 64% for those under the age of 62 years. Similarly, Rubin and colleagues⁵⁶ reported an average decline of 3 points in MMSE scores in elderly patients after completing two-thirds of ECT treatment; however, MMSE total raw scores returned to pretreatment levels by the time the patients completed the acute ECT course. A study by Bosboom and Deijen⁴⁶ evaluated a sample of 45 patients with MDD 1 week before ECT, 1 to 2 weeks after acute treatment, and at 6 and 12 months after ECT completion. During the course of treatment, participants completed a comprehensive neurocognitive battery that assessed attention, executive functions, memory, and intelligence. Although depression scores decreased across the treatment course, no reduction in depressive symptom severity was observed between sessions 2 and 3 or sessions 3 and 4, suggesting that any cognitive change found between those sessions could be attributed to the effects of ECT rather than to a change in depression severity. Because the authors found that performance on the neurocognitive battery improved between sessions 2 and 3 and sessions 3 and 4, they concluded that ECT may enhance cognitive functions.⁴⁶ These findings should be interpreted with caution, however, as performance could be affected by confounding variables such as the patient’s age and education level, and by practice effects.

Investigations have also explored the technical aspects of ECT treatment and cognitive function in elderly patients. For instance, Hihn and colleagues⁵⁷ compared the neurocognitive performance of 20 older patients with severe depression (mean age, 53.7 years; SD, 11.7) before and after an acute course of ECT. The study used the Wechsler Memory Scale–Revised⁵⁸ to assess for changes in immediate and delayed verbal and visual memory functions and in attention/concentration. Before ECT, patients revealed deficits in acquisition (immediate verbal and visual memory), attention/concentration, and retrieval of information (delayed memory). While a significant improvement was observed in immediate verbal, visual, and general memory functions following ECT, there was no correlation between ECT treatment parameters and improvement in long-term. The authors concluded that the more effective an ECT treatment course was for an individual, the more likely he or she was to experience improvements in immediate memory.

Long-Term Neurocognitive Effects
Although elderly patients often experience adverse cognitive effects from ECT, most are transient and resolve within a few weeks to months after the end of the acute course. Research suggests that anterograde and retrograde amnesia tends to resolve within 1 to 6 months, respectively.⁵⁹ Ng and colleagues⁶⁰ assessed the efficacy and cognitive effects of ECT in 32 patients with depression in a clinical setting using the Randt Memory Test⁶¹ to assess anterograde verbal memory function, the Personal Memory Test to evaluate autobiographic memory, and a self-rating scale⁶² to document reports of memory problems by the patient. Additionally, the study used the National Adult Reading Test (NART)⁶³ and the Wechsler Adult Intelligence Scale–Revised (WAIS–R)⁶⁴ to provide measures of intelligence. Patients were evaluated at baseline, after six treatments, at the end of the acute course, and 1 month after the acute course. While mean depression scores decreased by 54.2% from baseline to the end of the acute course, patients experienced impairment in immediate and delayed anterograde memory; however, within 1 month, patients showed normal performance on measures of anterograde verbal memory. Unlike the observed decline in anterograde memory, intelligence was unaffected by ECT, as reflected in consistent performance on the NART and the WAIS–R. Moreover, researchers observed an improvement in measures of subjective memory complaints and autobiographic memory, suggesting no long-term impact on those cognitive functions.⁶⁰ This is in contrast to prior research, which had suggested long-term retrograde amnesia for autobiographic⁵⁹ and public information,⁶⁵ but is consistent with new evidence that suggests that cognitive impairments resolve quickly after the last ECT session.⁶⁶

The long-term cognitive effects of ECT were also examined in 55 elderly patients who met the criteria for MDD.⁶⁷ These patients were divided into two groups: those with pretreatment cognitive impairment (n = 35) and those without it (n = 20). Depression was measured using the Hamilton Rating Scale for Depression (HRSD),⁶⁸ and overall cognitive functioning was assessed using the MMSE. Testing was conducted at baseline, 6 and 15 months following treatment, and again 4 years after the end of treatment. While those without pretreatment cognitive impairment did not show any significant changes in cognition at follow-up evaluations, results of the study suggested that patients with pretreatment cognitive deficits showed significant improvement in cognitive performance. At 4-year follow-up, 84% of patients exhibited a significant improvement in cognition and 79% retained remission, suggesting that ECT has positive long-term effects in elderly adults.⁶⁷ Additionally, a study by Russell and associates⁶⁹ supports the notion that ECT is efficacious and is not associated with long-term cognitive deficits. Using a retrospective chart review, the authors evaluated 43 patients over the age of 74 years who received maintenance ECT for more than 1 year. Cognition was assessed by comparing the MMSE scores at baseline with those after 1 year of treatment, which demonstrated mean MMSE scores of 25.31 and 21.84, respectively. Findings showed sustained clinical benefit and no clinically significant changes in cognitive performance, despite the decreased MMSE scores at follow-up.⁶⁹

Neurocognitive Effects in Patients With Dementia
Compared with nondepressed patients with dementia, those with MDD have a greater level of functional impairment and require additional care. Rao and Lyketsos⁷⁰ conducted a chart review of 31 elderly patients with dementia and secondary depression and analyzed the benefits and risks of ECT in these patients by comparing baseline and discharge MMSE and MADRS scores to determine cognitive functionality and depression severity. At baseline, patients showed moderate-to-severe cognitive impairment (mean MMSE score, 18.8) and had severe depression (mean MADRS score, 27.5). At the end of the ECT course, there was significant improvement in both depression and cognitive performance scores, as evidenced by a mean decrease in MADRS scores by 12.28 points and an increase in MMSE scores by 1.62 points. Specifically, 40% of patients were within the normal range on the MADRS (score ≤10) and 29% of patients improved by 5 points or more on the MMSE; however, of the 31 patients, 15 (48%) developed delirium at some point during the course of treatment. The duration of the delirium was transitory, lasting only 1 to 3 days, and the treatment team provided immediate and appropriate intervention.⁷⁰

Summary of Findings

Considerable progress has been made in the scientific and technical refinement of ECT, which has increased its efficacy and decreased its side effect profile.^18,71 The available literature, which is summarized in this review, suggests that ECT is associated with neurocognitive adverse effects in elderly patients, particularly in the memory domain, with specific effects of anterograde and retrograde amnesia; however, this is not unique to elderly cohorts, as similar neurocognitive adverse effect profiles have been found in nonelderly individuals.⁷² In addition, as found by Rao and Lyketsos,⁷⁰ the presence of dementia does not appear to increase the adverse cognitive effects of ECT, but cautious interpretation of these findings is warranted as the authors did not conduct a controlled investigation. Collectively, despite methodologic differences between studies and small sample sizes that limit generalizability, the available evidence suggests that ECT is safe and efficacious for elderly adults with MDD.

Depression and other sociodemographic variables such as age and education impact neurocognitive function^73,74; thus, it may be useful to include a neuropsychologic examination during the psychiatric and medical ECT examination to determine the level of cognitive function before initiating treatment.¹² This examination would provide a baseline assessment of cognitive ability, which can be used to compare performance on neurocognitive measures during and after the ECT course. Furthermore, it could help clinicians determine if the geriatric patient has the capacity to provide informed consent to receive ECT, and to establish what level of educational assistance the patient and his or her caregivers require regarding treatment.⁹

A commonality throughout the reviewed literature was the use of instruments to measure depressive symptoms and cognitive performance in the elderly adults with depression who were treated with ECT. This type of measurement-based care was used in the CORE studies,^31,36 with the clinician-rated depression severity measures (eg, 24-item HRSD⁶⁸) used to determine the number of ECT sessions provided during the acute course. A current investigation is exploring the use of clinician-rated depression severity measures and a global neurocognitive function measure to determine the number of ECT sessions to administer during the ECT continuation phase.⁷⁵ Such an individualized-dosing strategy (eg, each patient treated based on his or her clinical presentation) may be effective in preventing overtreatment or undertreatment by ensuring that the minimal number of ECT sessions needed to achieve remission and to minimize side effects are provided. For example, treatment teams can use depression severity measures, such as the Geriatric Depression Scale⁷⁶ or the 16-item Clinician and Self-Report versions of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16),⁷⁷ which have been validated to measure depressive symptoms specific to elderly adults. For neurocognitive measurement, treatment teams can use the MMSE or the Montreal Cognitive Assessment,⁷⁸ both of which allow global cognitive functions to be evaluated. While those two neurocognitive measures may be insensitive to select cognitive side effects associated with ECT (eg, retrograde amnesia), they can provide useful information regarding the impact on important cognitive functions, including orientation, attention, memory, and confrontation naming; see the report by Porter and colleagues⁷⁹ for a comprehensive review of neurocognitive assessment methods during ECT.

Conclusion

The neurocognitive effects associated with ECT may be comparable in adult and elderly populations. Careful monitoring of depressive symptomatology and neurocognitive functions are recommended during the treatment course to systematically guide the administration of ECT. Measurement-based care can help the treatment team individualize the ECT course for the patient, thereby improving the benefits of ECT while minimizing any associated side effects. Future investigations are warranted to assess the efficacy, effectiveness, and neurocognitive side-effect profile of ECT administered with measurement-based care practices in elderly cohorts. Research should focus on developing neurocognitive batteries specific and sensitive to ECT that can be used in clinical practice.

This publication was supported by Grant Number K23 MH087739 (Principal Investigator: Shawn M. McClintock, PhD) from the National Institute of Mental Health. Dr. McClintock reports research grant support from the National Institutes of Health (NIH), National Center for Research Resources, and National Alliance for Research on Schizophrenia and Depression. Dr. Husain reports research grant support from the NIH, The Stanley Foundation, Cyberonics, Inc., Neuronetics, Inc., St. Jude Medical, Inc., and The Magstim Company Limited. Ms. Staub reports no relevant financial relationships. Dr. McClintock is assistant professor, Neurostimulation Research Laboratory, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, and adjunct assistant professor, Division of Brain Stimulation and Therapeutic Modulation, Department of Psychiatry, Columbia University/New York State Psychiatric Institute, New York; and Ms. Staub is research associate and Dr. Husain is professor, Neurostimulation Research Laboratory, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.

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