Other Disorders That Cause Memory Loss or Dementia

In this chapter we present additional disorders that can cause memory loss and other cognitive impairment. Although some of these disorders are common, because none are causes of dementia per se, we touch on them here just briefly to round out the differential diagnosis of memory loss and dementia. These disorders are presented in the order that roughly corresponds to how often we see them in our clinic.

Quick Start

Depression and anxiety	• Although depression and/or anxiety may cause memory loss, many patients with memory loss and depression and/or anxiety have mild cognitive impairment or Alzheimer’s disease.
Medication side effects	• Medication side effects are one of the most common causes of memory complaints and cognitive dysfunction.
Disrupted sleep	• Disrupted sleep is one of the most common causes of memory problems we see in patients younger than age 60. • Sleep is needed in order to sustain attention when learning new information. • Evidence suggests that sleep is also necessary to consolidate memories from temporary to long-term storage.
Hormones?	• The literature is mixed regarding whether peri- or postmenopausal status is related to alterations in memory. • There are no randomized controlled trials of hormone replacement therapy showing a cognitive benefit.
Metabolic disorders	• Almost any medical disorder that makes a patient ill can cause memory loss and/or impair other aspects of cognition. • Metabolic disorders affect attention, wax and wane, and may unmask an incipient dementia.
Diabetes	• Diabetes can cause memory loss and other cognitive problems from cerebrovascular disease and hypoglycemia.
Alcohol abuse and alcoholic Korsakoff’s syndrome	• About half of the 18 million problem drinkers in the US develop some cognitive deficits. • Most patients with alcoholism complain of memory deficits. • Patients with alcoholic Korsakoff’s syndrome show severe anterograde and some retrograde amnesia.
Lyme disease	• Lyme neuroborreliosis is uncommon but highly treatable, and should be considered in those who live in an area endemic for Lyme who are at risk for deer tick exposure by, for example, taking walks in the woods. • The memory problems are typically secondary to difficulties with focusing and sustaining attention, leading to difficulties in encoding (learning).
Hippocampal sclerosis	• Hippocampal sclerosis is defined as severe gliosis and loss of neurons in the CA1 region of the hippocampus and neighboring regions. • Hippocampal sclerosis may occur by itself or with a wide variety of other diseases, including temporal lobe epilepsy, multiple sclerosis, Alzheimer’s disease, cardiovascular disease, frontotemporal dementia, and amyotrophic lateral sclerosis. • Clinically, we suspect that a patient may have hippocampal sclerosis if he or she shows evidence of memory dysfunction without other cognitive deficits, and the patient does not progress over time.
Subdural and epidural hematomas	• Subdural and epidural hematomas may cause a number of symptoms, including drowsiness, inattention, hemiparesis, or seizures, depending upon the size, age, and composition of the fluid collection.
Vitamin B12 deficiency	• Symptoms of B12 deficiency include memory loss, psychosis including hallucinations and delusions, fatigue, irritability, depression, and personality changes. • B12 deficiency should be suspected when the patient is elderly, a vegetarian, taking certain medications (e.g., metformin), or has had intestinal infections.
Seizures	• Seizures are an uncommon cause of memory problems but must be considered both because they are treatable and because they can lead to disability and death if they were to occur, for example, while driving a car. • Partial complex seizures should be suspected in patients of any age in whom there is a history of “episodes” of memory loss that may be quite profound in the setting of otherwise good memory and normal cognitive testing.
Human immunodeficiency virus (HIV)-associated neurocognitive disorder	• HIV can cause cognitive impairment, including apathy, slow processing speed, and executive dysfunction, with our without extrapyramidal motor features. • Consider this disorder in the patient with these cognitive signs and symptoms who has HIV-risk factors, as well as in the patient with known HIV disease.
Hashimoto’s encephalopathy	• Hashimoto’s encephalitis is a rare, rapidly progressing, treatable autoimmune disorder associated with chronic lymphocytic Hashimoto’s thyroiditis. • It often begins with psychiatric symptoms such as depression, personality changes, or psychosis, and then progresses with cognitive decline and one or more of a variety of signs and symptoms including myoclonus, ataxia, pyramidal and extrapyramidal signs, stroke-like episodes, altered levels of consciousness, confusion, and seizures. • Patients with Hashimoto’s encephalitis can be euthyroid, hypothyroid, or hyperthyroid.

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, was 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 due to the memory loss, rather than the other way around. In fact, studies suggest that 20–40% 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 (see Chapters 3 and 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, causing his or her memory loss.

Some of the most common cognitive disturbances due to depression include poor energy, motivation, and attention ( Fig. 14-1 ). 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 SSRI medication, sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro) being our favorites. Each of these medications has been approved for the treatment of both depression and anxiety. See Chapter 24 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. 14-2 ). 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. Box 14-1 lists some classes and properties of medications that can lead to cognitive dysfunction.

Box 14-1

Common Classes or Properties of Medications Causing Cognitive Dysfunction

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Allergy/antihistamines/common cold medications
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Analgesics including migraine medications
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Antiarrhythmics
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Anticholinergics
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Anticonvulsants
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Antidiarrheals
•

Antiemetics
•

Anesthetics
•

Antipsychotics/dopamine antagonists
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Antispasmodics/incontinence medications
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Asthma/pulmonary medications
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Barbiturates
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Benzodiazepines
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Beta-blockers
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Cancer chemotherapy
•

Corticosteroids
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Digoxin
•

Dopamine (Sinemet)/dopamine agonists
•

Muscle relaxants
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Opioids (narcotics)
•

Sedating medications of any class
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Sleeping medications of any class
•

Stimulants/stimulating medications of any class
•

Tricyclic antidepressants

Note: Worst offenders are in bold . This is not an exhaustive list. Please consult the Physicians Desk Reference or other source when determining whether a particular medication may be causing cognitive impairment in your patient.

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