Chapter 3: Memory Problems

Andres M. Kanner, MD; Alan B. Kantor, MD

CASE HISTORIES

Case 3-1. A 60-year-old woman with no complaints develops a gradual onset and progression of memory dysfunction according to her family. She has been unable to continue her work as a legal secretary for the past month. Her family states that she frequently repeats questions and forgets to take her hypertension medication. Mini-Mental Status Examination score (MMSE) is 24/30, and she has difficulty naming objects. She denies memory problems and depressive symptoms.

1. Where would you localize her neurologic problem?
2. What are the likely etiologies?
3. What would be your first step in evaluating this patient?

Case 3-2. A 45-year-old male professor suddenly becomes confused while giving a lecture. He continually asks orientation-type questions. He is able to respond to questions but does not know the date or place. This confusion completely resolves in six hours, and he is amnestic for the duration of the episode. His computed tomographic head scan is normal.

1. What is the most likely diagnosis?

DISORDERS

Complaints of "memory problems" are among the most frequent symptoms reported to internists by middle-aged and older adults. A fear of an impending dementing process, such as Alzheimer disease (AD), drives most of such complaints. Yet, the aging process is also associated with "normal forgetfulness." The clinician must be prepared to address such concerns and distinguish between a pathologic process resulting in memory disturbances and the "expected" changes in memory associated with a normal aging process.

When assessing a patient with memory dysfunction, the overall goal is to place the patient into one of three main categories: (1) age-associated memory impairment, which is normal; (2) minimal cognitive impairment (mildly abnormal MMSE score but normal function), which is between normal and dementia with as many as 10% to 15% of patients developing dementia within the next several years; and (3) dementia that is a global dysfunction of memory, language, and personality..

Memory is a very complex function and may be affected by numerous disorders. As in all neurologic disorders, the examination and time course are used to narrow down the possible etiologies. Table 3-1 categorizes etiologies of memory dysfunction based on time course and localization. These disorders are broken down into cortical and subcortical, which describe the major area of the brain affected.

Table 3-1 Neurologic Disorders Causing Memory Problems

Localization
Time Course	Cortical	Subcortical
Acute	Head trauma Anoxia Posterior circulation stroke Multi-infarct Transient global amnesia
Subacute	Tumor Normal pressure hydrocephalus Herpes encephalitis Hypoglycemia Creutzfeldt-Jakob disease
Chronic	Vitamine B12 deficiency Hypothyroidism Alzheimer disease Tumor Alcohol abuse Thiamine deficiency	Parkinson dementia Human immunodeficiency virus dementia Huntington chorea

Head trauma is a major cause of memory dysfunction. The patient develops anterograde (inability to acquire new information) and retrograde (unable to retrieve information obtained in the past) amnesia. With time, these deficits decrease but the patient does not regain memory of the accident. Memory loss can be caused by an infarct of the medial temporal lobes in a posterior circulation infarct or from multiple large hemispheric infarcts (multi-infarct dementia). Transient global amnesia is a disorder of unknown etiology that causes sudden anterograde amnesia, and when the episode resolves in less than 24 hours patients have retrograde amnesia. During the episode the patient continually asks orienting-type of questions but is able to respond and perform complex activities like driving. Normal pressure hydrocephalus is a clinical triad of memory loss, urinary incontinence, and a gait disorder characterized by slow-velocity short steps with low height. Herpes encephalitis is a treatable disorder with the subacute onset of fever, headaches, behavioral changes, focal signs, and seizures. Creutzfeldt-Jakob disease causes a rapidly progressive dementia over months and myoclonic jerks, especially with auditory or tactile startle. Alzheimer disease causes a gradually progressive decline of primarily memory and language functions along with behavioral changes. Gradually progressive dementia, chorea, and a family history for similar deficits are suggestive of Huntington chorea.

HISTORY

In addition to determining the suddenness of onset of the symptom, important historical points for evaluation of memory disturbances are described in Table 3-2.

Table 3-2 Important Historical Points

System	Ask the Patient and Observer
Medical	Human immunodeficiency virus (HIV) status, alcohol use
Transient global amnesia	Repeated orienting questions, able to respond to questions and perform complex motor activities
Neurologic	Urinary incontinence and gait disorder (normal pressure hydrocephalus) Myoclonic jerks (Creutzfeldt-Jakob disease) Personality change Function Depressive symptoms: anhedonia, terminal insomnia Progressive headaches (tumor) Focal weakness/numbness (tumor) Language disturbance

EXAMINATION

The mental status examination begins when the patient enters the examination room. Note how the patient interacts with you and whether the behavior is appropriate. One of the most important questions to ask patients in an open-ended fashion is whether they are having any difficulties. Patients with depression complain bitterly of memory difficulty. Patients with dementia most often do not realize they have a memory problem. A standard MMSE should be performed, noting the patient's education level and age. During the remainder of the neurologic examination one should look for focal findings such as weakness or numbness on one side of the body or reflex asymmetry. Involuntary movements such as myoclonic jerks, chorea, or a rest tremor should be noted. Other Parkinson features (see chapter 8) in addition to rest tremor are bradykinesia, rigidity, and difficulty with the center of gravity.
CLUES TO DIAGNOSIS

One of the most common causes of memory dysfunction is depression, which causes a bitter complaint of memory difficulty along with vegetative signs of depression. Sudden onset and resolution of memory problems, confusion, and repeated orienting questions are very suggestive of transient global amnesia. Subacute memory difficulty over hours or several days with seizures is seen in herpes simplex encephalitis. A family history of chorea and dementia along with the observation of chorea in the patient should suggest Huntington chorea. A rapid onset of dementia with myoclonic jerks that occur especially when the patient is startled with a loud noise or touch is seen in Creutzfeldt-Jakob disease.

RED FLAGS AND WHEN TO REFER

In general, the more rapid the onset of memory difficulty the more rapid the workup and referral should be (Table 3-3).Patients with acute memory loss should be immediately referred to the neurology department. If there is gradual onset and progression of memory dysfunction, then the patient could see a neurologist on a routine basis. Be aware of any subacute memory loss with fever, focal findings, or seizures that could represent the treatable disorder of herpes simplex encephalitis. Patients who are depressed should be referred to the psychiatry department. If there is a question of whether memory difficulty is caused by dementia or depression, neuropsychological testing can be helpful.

Table 3-3 Time Frame for Evaluation and Referral

Evaluate and Refer	Onset of Symptoms
Immediate	Acute	Subacute	Chronic
	Sudden memory loss with or without focal findings Memory loss with fever, headache, focal findings, seizures
Within 72 hours		Subacute memory loss without focal findings
Within 2 weeks			Gradual onset of memory loss

CASE DISCUSSIONS

Case 3-1. Important features of this case include the patient's lack of insight into her memory problem, no depressive symptoms, low MMSE score, and inability to function. This constellation of findings suggests a dementia involving primarily the cortex and is compatible with dementia of the Alzheimer type. The first step in evaluating this patient is to rule out treatable causes with a brain magnetic resonance imaging (MRI) and blood testing for vitamin B12 and thyroid function.

Case 3-2. This is a very characteristic history for transient global amnesia, which causes the sudden onset of confusion and repeatedly asking orienting-type questions with preserved complex motor function. A seizure is not likely since the patient can respond to questions, although the answers are often incorrect.
CME QUESTIONS

1. A 56-year-old male accountant began to have some difficulty with remembering words while conversing with coworkers. His employer has had complaints of some errors in the patient's accounting work, and his handwriting has deteriorated. His wife mentions that he has started to ask the same question repeatedly. On examination he has mild difficulty naming small parts of objects, and his MMSE score is 24/30. He denies depression. What is your first concern in this patient?

a. Anterograde amnesia
b. Herpes encephalitis
c. Mild cognitive impairment
d. Possible left hemisphere lesion

2. A 45-year-old woman presents reporting memory difficulty. She is able to function at work as a teacher and at home, but she has to make lists so that she will not forget what she needs to accomplish. She denies depression. On examination her MMSE score is 27/30. What is the most likely diagnosis in this patient?

a. Age-associated memory impairment
b. Dementia
c. Limbic encephalitis
d. Mild cognitive impairment

3. A 36-year-old woman developed fever and headache starting 4 days prior to admission. She has also been observed to be staring into space and is unresponsive during these 1- to 2-minute episodes. On examination she is easily distracted and has mild weakness of her right arm and leg. What is the most likely diagnosis in this patient?

a. Creutzfeldt-Jakob disease
b. Early-onset dementia
c. Herpes simplex encephalitis
d. Posterior circulation stroke

4. A 40-year-old woman with a family history of Alzheimer disease presents reporting severe memory difficulty. She cannot remember what she is reading or typing at work as a secretary; however, no one has noticed a problem. At home she has great difficulty remembering what to purchase at the store. She does have some difficulty awakening from sleep around 3:00 a.m. and not being able to fall back to sleep, but she vehemently denies depression. Her MMSE score is 30/30. What is the most likely cause of her memory complaint?

a. Depression
b. Early dementia
c. Mild cognitive impairment
d. Possible HIV dementia

5. A 62-year-old man is referred for balance difficulty. His wife reports that over the past several months he has started having difficulty with his memory for recent events. She also reports that he occasionally has urinary incontinence. On examination his MMSE score is 24/30, and he has slow, short steps with low height. What is the most likely diagnosis?

a. Benign prostatic hypertrophy
b. Early-onset Creutzfeldt-Jakob disease
c. Normal pressure hydrocephalus
d. Parkinson disease

CME ANSWERS
1. d. possible left hemisphere lesion
2. d. mild cognitive impairment
3. c. herpes simplex encephalitis
4. a. depression
5. c. normal pressure hydrocephalus

Chapter 3: Memory Problems

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