Patient H


The following is adapted from a case presented in the New England Journal of Medicine.
New England Journal of Medicine (2017) "Case 1-2017-An 70-Year-Old Woman with Gradually Progressive Loss of Language" 376: 158-167

A 70-year-old woman was seen in the memory disorders clinic of this hospital because of progressive cognitive difficulties involving word finding. She was interviewed with the assistance of her daughter.

The patient had reportedly been well until approximately 8 years before this evaluation, when gradually progressive difficulties with word finding developed, along with associated confusion about the meaning of some words. For example, during a conversation about a recent family event, she did not understand what the phrase “punch bowl” meant....She had a good memory for recent events of her life and could recount multiple stories (at times to an excessive extent during history taking, such that she required refocusing). She had an excellent sense of direction.

Since the death of her husband 10 years earlier, she had lived alone (in a different state than her daughter) and was able to perform all activities of daily living independently, including managing her money, paying bills, and volunteering in the community (i.e., visiting senior centers to play piano and attending regular community choir practices).

The patient was right-handed....There was no history of recent head injury, stroke, seizure, transient ischemic attack, meningitis, encephalitis, exposure to human immunodeficiency virus, thyroid disorder, heart disease, hypertension, hyperlipidemia, diabetes mellitus, liver disease, kidney disease, cancer, pulmonary disorders, exposure to heavy metals, or learning disability.

As part of the standard evaluation for a suspected cognitive impairment, the patient was referred for neuropsychological testing, speech pathological evaluation, and imaging studies of the head.

Below is the evaluation by the neuropsychologist.

Language impairment was evident both through clinical observations and when she performed verbal tasks, including tasks of confrontation naming, verbal fluency (for which she had substantially more difficulty with semantic fluency than with phonemic fluency), verbal abstraction, and comprehension of individual words.  Her spontaneous speech was fluent, but she had notable difficulty with word finding and made occasional paraphasic errors. She often had difficulty comprehending words, such as “cork,” “misplaced,” “bored,” and “pessimism.”...Her performance was normal on a test of nonverbal memory but was substantially impaired on a test of verbal memory....She did not report symptoms of depression or anxiety on self-reported assessments.

In a confrontation naming test, the patient is shown a picture of an object and asked to supply the word.

In a verbal fluency test, the patient is asked, during a limited time period, to name as many words as possible from a particular category (semantic fluency) or beginning with the same letter (phonemic fluency).  "Semantic" is an adjective that means related to meaning in language.  "Phonemic" refers to phonemes, which are the units of sound that make up language.  For instance, the words "cat" and "bat" differ by the phonemes that begin each word. 

Paraphasias are language errors that occur when the patient inserts the wrong sounds or syllables in a word, substitutes the wrong word, or sometimes speaks nonsense words.

Below is the evaluation by the speech pathologist.

Speech pathological evaluation revealed that the patient had fluent, articulate speech with pauses for word finding, vague word substitutions, and circumlocutions. She was somewhat tangential in her speech and was fixated on telling stories from her life, such that she required frequent refocusing on the topic at hand. She had substantial impairment on a test of naming, with superordinate responses, and she had impairment on word–picture matching. Rare phonemic paraphasias were present. Auditory comprehension was impaired for words she no longer recognized and for sentences with complex syntax. Sentence repetition was intact. A written language assessment revealed that she could read normally and had mild agrammatism in written language samples. A semantic picture–picture matching test revealed no evidence of visual agnosia.

Circumlocution means literally to "speak around". The patient is unable to find a specific word and instead uses many words to describe it.

A superordinate response is one where instead of giving the specific name, the patient gives the category name. For example, if shown a picture of a cup, she might say "dish" instead.

Agnosia (literally "without knowledge") is a term that is used when there is a defect in recognition. For instance, visual agnosia would be an inability to recognize an object presented visually, even though other aspects of vision are normal.

This patient has a cognitive impairment that is specific to language ability. What is the term for this?

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Which description is most appropriate in her case:  "expressive" or "receptive"?

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What characteristics of this patient differ from classical Wernicke's aphasia?

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Aphasia occurs as a result of damage to specific parts of the brain, almost always in the left hemisphere, especially in a patient such as this one who is right-handed.  The most common cause of aphasia is brain damage due to stroke, but other types of brain damage can cause aphasia.

This patient has been experiencing symptoms that have steadily gotten worse over the course of 8 years. The gradual, progressive nature of this patient's aphasia suggest to her doctors that she is suffering from a neurodegenerative disease.

In what ways does this patient differ from a patient with dementia due to Alzheimer's disease?

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This patient's aphasia is characterized by difficulty with object naming and word finding, a dysfunction that is known as anomia. As well, she has a striking deficit in word comprehension.

MRI of the head...revealed asymmetric volume loss of the left temporal lobe — especially its anterior and medial aspects, including the subcortical white matter, amygdala, and hippocampus — along with corresponding dilatation of the left temporal horn.

Four months after the patient’s initial evaluation, FDG-PET revealed hypometabolism of the bilateral frontal lobes asymmetrically and of the bilateral temporal lobes that was greater on the left side than on the right side.

The loss of neurons due to neurodegenerative disease can result in significant atrophy that may be visible on an MRI scan. This is what was observed in this patient, particularly in the anterior temporal lobe on the left side.

FDG-PET is a technique to look at brain activity indirectly.  FDG (fluorodeoxyglucose) is a radio-labelled glucose analog whose accumulation in tissues indicates glucose uptake.  A less than normal degree of labeling indicates decreased metabolism and therefore decreased neuronal activity.  The FDG-PET in this case indicates reduced neuronal activity in the left frontal and temporal lobes.

On the basis of the long time course, we can confidently conclude that she had the syndrome of primary progressive aphasia, an acquired language disorder caused by a neurodegenerative process, with relative preservation of other domains. In contrast to typical dementias that occur in late life, primary progressive aphasia most commonly starts before 65 years of age and is not associated with memory loss.

The semantic variant [of primary progressive aphasia] is characterized by impairment of object naming and word comprehension in the setting of preserved fluency, repetition, and grammar...The most distinctive feature of this patient’s presentation is the loss of word comprehension, a finding that most closely fits the semantic variant of primary progressive aphasia.

Primary progressive aphasia is considered a form of dementia, since it causes gradual cognitive decline. However, it is distinguished from other dementias because early in the disease (for at least the first 2 years, but sometimes longer), the cognitive deficits are specific to language ability. As the disease progresses, language impairment worsens, and other cognitive functions start to decline. That was the case with this patient who moved to an assisted living facility 2 years after this evaluation. Over the next 6 years, her symptoms progressed until she could no longer walk or carry out basic activities of daily living. She had advanced-stage dementia when she passed away at the age of 78.

The classical language model is based on studies of patients with aphasia occurring as a result of strokes. Branches of the middle cerebral artery supply Broca’s and Wernicke’s areas, and occlusion of these branches can cause ischemia and focal damage leading to expressive or receptive aphasia. However, modern functional imaging studies have shown that the network of structures involved in language processing is more distributed, involving brain regions beyond Broca’s and Wernicke’s areas.

This patient with the semantic variant of primary progressive aphasia (PPA) has damage in the anterior temporal lobe. Studies of patients with this type of PPA have illustrated that the anterior temporal lobe is a key region in the language network that is important for the task of linking words to their meanings.