Other Disorders That Cause Memory Loss or Dementia

Depression and Anxiety

It is quite common that we will see a patient with memory loss or mild dementia who was treated with an antidepressant rather than a cholinesterase inhibitor by their primary care physician. The typical scenario is that the patient noticed that they were beginning to lose their memory, were concerned that they might be developing Alzheimer’s disease, and understandably felt quite concerned, anxious, and depressed about their memory loss. The physician, correctly picking up on their anxiety and depression, prescribed an antidepressant. In our experience it is much more likely that a patient who is over the age of 65 and presents with both memory loss and depression has depression because of the memory loss, rather than the other way around. In fact, studies suggest that 20% to 40% of patients with dementia also have major depression, and up to 70% of patients have some depressive symptoms ( ).

It used to be a rule of thumb that patients who do not think that they have memory problems have Alzheimer’s disease, whereas patients who are worried about their memory problems are aging normally or are depressed. Now we believe that it is much more likely that patients who are worried about their memory problems actually have mild cognitive impairment or very early Alzheimer’s disease dementia (see Chapter 3, Chapter 4 ).

The relationship between Alzheimer’s disease and depression is both complex and controversial (for review see ). Studies have suggested that (1) a history of depression earlier in life is a risk factor for Alzheimer’s disease and (2) symptoms of depression are common in the few years preceding the diagnosis of Alzheimer’s disease, prompting some researchers to hypothesize that it is an early symptom of Alzheimer’s disease, especially in individuals with no lifetime history of depression ( ).

The history is one important clue to help determine whether the memory loss or the depression is primary. It would be extremely unlikely that a 75-year-old patient without a prior history of major depression would now develop a first episode of major depression severe enough to cause memory problems. On the other hand, a patient with a lifelong history of major depression severe enough to lead to multiple hospitalizations and medication trials may certainly be experiencing another episode of depression at age 75 years, causing his or her memory loss.

Some of the most common cognitive disturbances caused by depression include poor energy, motivation, and attention ( Fig. 17.1 ). Frontal/executive and speed of processing deficits are often found on neuropsychological testing. Memory problems are typically secondary to these disturbances. Depression and anxiety disrupt the “file clerk” of the memory system, whereas Alzheimer’s disease disrupts the “file cabinet.” In other words, the patient with depression has difficulty placing (storing, encoding) information in the memory (the file clerk isn’t doing its job), but, once it is stored, the brain mechanisms that maintain the memory are intact (the file cabinet is fine). (See Appendix C for more on the filing analogy of memory.) Thus patients with depression may appear to have a “frontal pattern” of memory loss, often performing poorly in learning (encoding) and freely recalling information off the top of their head, while performing relatively normally when choosing previously studied items from a list. Another pattern that is sometimes present in patients with depression is that they experience more difficulty remembering things in the past than the present. This pattern is thought to occur because it is more effortful for a person whose memory is normal to recall items from the distant past than to recall events that occurred yesterday. This pattern is just the opposite of that of most patients with Alzheimer’s disease, in which the patient recalls the past easily but cannot remember what happened yesterday.

In treating a patient who has both memory loss and depression, we always recommend treating the underlying disorder first. This recommendation may seem obvious, but many clinicians suggest treating the depression first regardless of whether it is primary or secondary. In our experience the depression secondary to awareness of memory loss typically improves when the memory improves. Similarly, the cognitive impairments secondary to depression generally improve when the depression is treated. Each patient may still benefit from a medication to treat the secondary symptom. For example, the patient with memory loss and secondary depression may still benefit from an selective serotonin reuptake inhibitor medication, sertraline (Zoloft) and escitalopram (Lexapro) being our favorites. Each of these medications has been approved for the treatment of both depression and anxiety. See Chapter 27 for more on the pharmacological treatment of depression.

Medication Side Effects

Medication side effects are one of the most common causes of cognitive dysfunction ( Fig. 17.2 ). In our experience, attention is the most common cognitive function to become affected, followed by memory, and then language. There are too many medications that interfere with cognition to individually list them all. Note that even a relatively safe class of medication from a cognitive perspective may still contain a few individual drugs that can cause confusion. Boxes 17.1 and 17.2 list some classes and properties of medications that can lead to cognitive dysfunction.

Disrupted Sleep

Disrupted sleep is one of the most common causes of memory problems we see in patients younger than age 60 years. Poor sleep can disrupt memory in two main ways. First, sleep is necessary for good attention. To encode or learn new information, being able to focus and sustain attention is critical. Second, consolidation of memory—memories going from temporary to more long-term storage—requires sleep ( ). Thus poor sleep makes it difficult to learn new information and to retain that information in long-term storage.

Disrupted sleep may be the result of a sleep disorder such as insomnia, sleep apnea, periodic limb movements of sleep, and restless leg syndrome. Sleep may be disrupted by depression. And sleep may be commonly disrupted by poor sleep cycle or hygiene—that is, poor scheduling or management of sleep.

Shift workers, including nurses, factory workers, and others, are one group that is prone to memory disorders because of poor sleep hygiene. However, in our experience even more common than shift workers are individuals of any age who simply have too many things to do in their day to allow enough time for adequate sleep. When we are referred individuals with memory problems who are in their 30s or 40s, we always ask about sleep problems in several different ways. When asked, “Do you have any problems with sleep?” the response is usually no. But when asked to briefly take us through their day, a common response often goes something like the following. “I’m up at 5 am to exercise, shower, and get myself ready for work at 6, get the kids up and get them ready for school at 7, and then leave for work at 8. I come home from work around 6 pm , make dinner, help the kids with their homework, and get them ready for bed by 9. Then I usually spend an hour or two finishing up work for the office, and then at 10 or 11 I have an hour or two to spend some time with my spouse talking or watching TV, till we go to bed after the evening news around 11:30 or 12.” Although this may sound like a perfectly normal schedule, this individual is only allowing themselves between 5 and 5½ hours of sleep a night. For the average individual, who is best with 8 hours of sleep, one can often get away with 7 hours without noticeable cognitive consequences. But trying to reduce sleep further often causes difficulty with attention and memory.

Hormones?

Another possible cause of memory problems in individuals younger than age 60 years is a decrease in gonadotropin hormones. For women this is most commonly because of perimenopausal status; for either women or men this can be secondary to treatment for cancer or other disorders. The literature on this topic is quite mixed, with some studies demonstrating memory impairment and other studies not, and at least one literature review suggests that the natural transition to menopause is not associated with objective change in episodic memory ( ). Nonetheless, many individuals who come to us in the clinic are quite clear about their subjective experience that their memory is not as good as it was previously, which they relate to a change in their hormone status.

Regarding treatment, the literature again shows mixed results, with some studies finding improvement with hormone replacement therapy and others not, and literature reviews suggest that there is no improvement ( ). Most importantly, however, large randomized controlled trials have now shown no evidence for improvement and instead worsening of cognition and increased risk for dementia with hormone replacement therapy ( ).

In summary, despite historical claims that hormone replacement therapy has cognitive benefit, we now know from randomized controlled trials that there is no evidence for this claim, and indeed there are increased risks for dementia and other disorders. As such, we do not recommend hormone replacement therapy for postmenopausal women solely as a treatment for memory problems.