Mrs. Lee is a 50-year-old Asian woman with normal cognitive function and a family history of Alzheimer disease (AD). She wishes to delay cognitive decline and to prevent or delay dementia but wants to avoid medications and use “natural” therapies instead. How would you advise her?

Mr. Ortego is a 58-year-old Hispanic man with mild cognitive impairment (MCI). His wife would like to help improve his memory function and his ability to perform daily activities. How would you guide them on complementary and alternative medicine (CAM) or nonpharmacologic therapies for preserving or improving cognitive function?

Ms. Rosenthal is a 65-year-old white woman with early AD who currently resides in an assisted living facility. The facility staff is concerned that she has intermittent behavioral agitation while on a cholinesterase inhibitor. Her caregiver would like a nonpharmacologic intervention to reduce agitation. What would you suggest as a start?

Cognitive Impairment in Older Adults

Older persons account for an increasing proportion of the adult population and are expected to comprise 25% of the total US population within 20 years.[1] Worldwide, 35.6 million persons are living with dementia.[2]Increasing age is associated with a higher prevalence of cognitive decline. Cognitive symptoms are a concern in 3%-15% of older adults.[3]

Mild cognitive impairment (MCI) is cognitive impairment with sound functional capacity and isolated memory impairment without dementia,[4-6]although finer aspects of functional impairment have been described in this group. The most prevalent type of MCI is classified as amnestic, or related to memory. The prevalence of MCI in older adults is estimated at 3%, and 3% of those with MCI go on to develop AD; in comparison, only 0.5% of persons without MCI develop AD among the general population.[7,8]

Cognitive impairment is also associated with chronic and acute medical conditions and with such treatments as chemotherapy.[9] In these settings, impairment is often undetected or underrecognized. Even early cognitive impairment can adversely affect mortality and quality of life through heightened risk for comorbidities, such as falls and fractures.[10,11]

Although there is no known cure for AD, delaying disease onset by 6 months will reduce its incidence by 6%, and delaying it by 5 years will reduce its prevalence by 44%.[12] Hence, there is intense interest in therapies that may delay cognitive decline among both cognitively normal adults and those with MCI.

IS CAM A THERAPEUTIC OPTION?

CAM is widely used in the United States and globally[13] and is also used by older adults.[14]Data from the National Health Interview Survey suggest ethnic variation in CAM use: More than one quarter of US adults older than 65 years report use of CAM; women report greater use than men; and use is highest among Asian persons (49%), followed by Hispanic (32%), white (28%), and black persons (21%).[15]

In a study of older adults (mean age 73 years, two thirds female) attending clinic for dementia and MCI, 47% of patients compared with only 18% of controls without MCI or dementia reported use of CAM therapies for memory disturbances; vitamins were most commonly used, followed by herbal preparations.[14] Herbal preparations included garlic, ginseng, magnesium, and omega-3 fatty acids. In this study, 90% of patients surveyed reported positive attitudes toward conventional medicine and 52% were currently receiving conventional medications. However, over one half of patients did not report their use of CAM to their physicians. Use of CAM was not correlated with education, disease severity, insurance status, or profession.

Multiple factors account for CAM use, including sociocultural, spiritual, and holistic beliefs, so that providers cannot readily predict CAM use among patients.[16] Clinicians must inquire about CAM use in all patients, particularly those more likely to experience medication interactions, such as older patients with multiple comorbidities.

Can We Prevent Cognitive Decline?

There is currently no pharmacotherapeutic approach for preventing cognitive decline in persons with normal cognitive function. Citicoline, a psychostimulant, recently showed some promise for vascular cognitive impairment and vascular dementia after stroke.[17]

Cognitive Interventions. Cognitive interventions or exercises comprising cognitive and memory training, cognitive and memory stimulation, cognitive rehabilitation, and neuropsychological intervention have been collectively found to be of benefit in slowing cognitive decline in 3 recent systematic reviews.[18-20]

Computer programs used by adults without AD or MCI who are older than 55 years have been shown to be comparable to pen-and-paper cognitive interventions and hold promise for preserving cognitive function.[1] These online programs may increase access to preventive treatment.

Exercise. Among persons with MCI, moderate levels of exercise have been shown to reduce the rate of decline of cognitive function.[21]

Nutritional Therapies. Vitamin D deficiency was reported to be associated with an increased risk for MCI (odds ratio, 2.4) in cross-sectional and longitudinal studies, although large randomized trials of vitamin D supplementation are needed to assess whether supplementation reverses the effect.[22]

Multivitamins were examined in another analysis of 10 clinical trials involving 3200 participants.[23]Among adults with intact cognition and memory, multivitamin supplementation was associated with enhanced immediate free recall memory. However, no other cognitive domains, such as delayed recall or verbal fluency, were improved. Studies were of short duration (less than 12 months), and the authors of the meta-analysis speculated on the potential of multivitamins for preserving a limited aspect of memory recall but concluded that the impact on delaying cognitive decline was unclear.

Higher intake of omega-3 fatty acids has been associated with lower risk for both AD and MCI, but findings from interventional trials are inconclusive. A meta-analysis of 10 randomized controlled trials in persons with normal cognitive function, MCI, or AD found a benefit in the domains of attention and processing speed. No benefits were found for persons with normal cognitive function or with AD, but only for those with MCI.[24] In particular, vitamin D supplementation did not improve global cognitive performance, recognition or working memory, executive function, or immediate or delayed recall in any of the 3 groups.

Herbal Preparations and Other Therapies. An older review examining the use of herbal preparations for AD reported a potential for ginkgo biloba to slow memory loss but found inconclusive evidence for other preparation.[25]Studies were limited by the fact that these preparations were not compared with current pharmacologic treatments for AD and dosages were not standardized among studies.

A more recent review reported that ginkgo biloba did not prevent dementia in elderly persons and did not improve cognition among those with dementia.[9] Ginkgo biloba may increase bleeding risk, especially in older persons using warfarin or aspirin. A systematic review of Chinese herbal medicines reported that 3 of 10 randomized trials found a benefit of these agents equivalent to that of piracetam on Mini-Mental State Examination scores.[26] The authors concluded that further studies were warranted.

Aromatherapy, both inhalational and topical used during massage, for AD patients with behavioral agitation was examined in a systematic review of 11 trials with a total of 405 patients.[27]Aromatherapies consisting of essential oils (such as lavender, lemon, rosemary, chamomile, or orange) were applied daily for 1 day to 16 weeks in AD patients. The reviewers concluded that the frequency of agitation was reduced and social engagement and independence in daily living tasks improved among patients with dementia exposed to the therapy.

Are There Other Options? Other CAM modalities used to improve cognition include meditation; manual therapy, such as haptotherapy and massage; and mind/body techniques, such as relaxation and biofeedback. These methods appear to improve general well-being and reduceanxiety or depression, rather than act directly on cognition.[9]

In summary, CAM use for cognitive function among older adults is common but underreported and may interfere with concurrent medication use. Patients wishing to improve or sustain cognitive function are likely to use multivitamins; vitamin D; and herbal preparations, such as ginseng and ginkgo biloba. However, the evidence for the efficacy of these modalities is limited and inconsistent. Providers should ask about CAM use in their patients and stay current on the evidence for the efficacy of emerging CAM modalities to appropriately advise their patients.

BACK TO THE CASES

The 3 patients all present for advice about cognitive function. It is likely that Mrs. Lee has already tried some CAM therapies. Each patient should be asked about current and past use of CAM. Their beliefs about conventional medicine and holistic care should be explored and negotiated before recommendations are given.

For adults with normal cognitive function, such as Mrs. Lee, omega-3 fatty acids and herbal preparations, such as ginseng or ginkgo biloba, are unlikely to prevent cognitive decline. For those with vitamin D deficiency, as determined by serum levels of 25-hydroxyvitamin D, supplementation may prevent cognitive decline. Multivitamins may enhance immediate free memory recall but not other domains of cognition. Instead, Mrs. Lee may wish to begin cognitive training exercises and to consider strategies to maintain general psychological well-being, such as mind/body techniques, to preserve her cognitive function. A moderate level of exercise has also been shown to preserve cognitive function, among many other benefits.

Mr. Ortego may benefit from omega-3 fatty acids to improve immediate recall, attention, and processing speed but not memory function.[24]There is little evidence to support the use of multivitamins or vitamin D supplementation in patients with MCI who are not deficient in vitamin D to prevent progression to AD. He may wish to engage in cognitive training and moderate levels of physical activity, because there is evidence for some benefit from these approaches.

Ms. Rosenthal already has AD for which she is receiving pharmacotherapy. Before adding medications for agitation, her caregiver may wish to consider the use of daily aromatherapy to reduce agitation and improve her engagement in daily life.

In short, advice for each patient needs to be tailored for the patient’s current cognitive status, current use of medications and other CAM therapies, need for other preventive approaches, and individual beliefs and cultural and social factors.

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