Alzheimer's: Diagnostic Testing and Counseling About Memory
Case

A 57-year-old woman came to our office with her daughter, who was concerned about her mother’s memory. The patient, too, was agitated and confessed to bouts of forgetfulness and confusion. As clinicians, we know that many peri- and postmenopausal women are anxious about loss of memory, but how should we counsel them on options to both preserve memory and decrease the risk of memory loss? What diagnostic testing is available to identify who may in fact have early-onset Alzheimer’s disease?

Management Issues by Robert Krikorian, PhD

Complaints about memory are common from women during peri- and postmenopause. Such complaints may represent different conditions, and distinctions can be made between the underlying bases for complaints generated during these developmental periods.

Perimenopausal memory complaints tend to be associated with hormonal variations and often are correlated with the occurrence of other perimenopausal symptoms such as hot flashes. There is relatively little empirical study of memory during perimenopause and very little objective assessment of memory function to determine whether these complaints are concomitants of other symptoms or represent genuine impairment of cognitive function. On the other hand, there is ample evidence that subjective memory complaints during perimenopause are associated with perceptions of overall health, stress level, and mood. For many women, symptoms associated with variations in reproductive hormone levels tend to subside after menopause, and subjective memory complaints would follow this pattern.

Postmenopausal memory complaints are common as well and often are associated with increased anxiety, depression, or both. However, they should be taken more seriously. Subjective memory complaints in post-menopausal women can represent nonspecific, age-related cognitive decline, often termed “age-associated memory impairment,” but also may represent early neurodegeneration and increased risk for progression to dementia.

Brief office examinations to assess memory function can be readily learned and administered by nursing staff and physicians. Such examinations might include the Montreal Cognitive Assessment (MoCA) or the Modified Mini-Mental State Examination (3MSE), among others. These instruments can be administered in about 5 minutes and provide a rough, objective screening of memory function and other cognitive abilities. Another measure that assesses memory and cognitive effectiveness in the context of everyday functioning is the Clinical Dementia Rating (CDR). This instrument requires more time with the patient as well as access to information concerning everyday activities provided by an informant. If the symptom information suggests memory decline, especially when corroborated by an informant, or if performance on the screening measure is below expectation, then referral for formal neuropsychological evaluation is indicated to document the nature and extent of cognitive impairment. Additional follow-up involving neurological consultation and/or brain imaging is a consideration contingent on the results of the neuropsychological examination.

Between 60% and 80% of cases of dementia involve Alzheimer’s disease (AD). In the United States, the prevalence of AD is projected to increase from 5.3 million to 16 million cases by the year 2050. This impending dementia epidemic is temporally but also etiologically related to the current obesity epidemic. The common etiological factor is compensatory hyperinsulinemia caused by insulin resistance. Peripheral hyperinsulinemia is associated with central hypoinsulinemia because of saturation of receptor-mediated insulin transport across the blood-brain barrier. Central hypoinsulinemia will result in increased expression of pro-inflammatory cytokines and increased β-amyloid generation as well as reduced neuroplasticity, all of which are important factors driving neurodegeneration. Given these adverse effects of metabolic disturbance, important signs of risk would include elevated waist circumference (especially >100 cm) or fasting insulin value in the hyperinsulinemic range or both. These indicators, when coupled with lower performance on a cognitive screening measure, should heighten concern and hasten referral for more comprehensive evaluation.

Available pharmacological therapies have little impact on dementia. However, prevention or mitigation of the neurodegenerative process in the early predementia stage often is feasible. This is why early identification is so important. Dietary approaches are the most effective interventions because dietary factors represent the most potent determinants of metabolic function. Carbohydrate restriction is extraordinarily effective in correcting hyperinsulinemia. Augmentation with an insulin-sensitizing agent also is a consideration, if necessary. Improving metabolic health, controlling insulin level, and avoiding cardiovascular risks and type 2 diabetes can reduce risk for progressive neurodegenerative disorders as well as improve general health.

With respect to the case under discussion, and assuming there is no other contributing factor such as thyroid disease, syphilis, or pernicious anemia, if there is an indication of memory decline in the context of one or more of the signs of metabolic disturbance, we might prescribe a dietary approach in addition to referral for more definitive cognitive evaluation. We would presume that at age 57 very early decline has been identified and that intervention might forestall progression. Chances for success in this regard diminish with advanced age because, in general, neurodegeneration progresses with aging in susceptible individuals and will reach a point of irreversibility. Other lifestyle factors that hold promise as moderators of neurodegeneration include exercise such as cardiopulmonary training but especially resistance or strength training designed to build and maintain muscle mass, as well as maintaining social involvement and recreational pursuits.

While subjective memory complaints are quite common, they sometimes represent the earliest manifestation of neurodegeneration, particularly when they occur in the postmenopausal period. However, the appearance of memory complaints also represents an opportunity to identify the at-risk individual and to institute interventions that may forestall progression.

From the NAMS Menopause e-Consult newsletter, Volume 6, Issue 1, January 2010
For more, please visit http://www.menopause.org/news.aspx