A Case of Primary Progressive Aphasia Progressing to Severe Dementia and Death
ABSTRACT: Primary progressive aphasia (PPA) is a rare neurodegenerative disorder characterized by an isolated and gradual dissolution of language function that progresses to dementia. This is a case study of a 70-year-old male who was diagnosed with progressive nonfluent aphasia in 2003. Eight years later, he had a marked decline in his condition, ultimately progressing to dementia and death. This article reviews the clinical features of PPA, risk factors, diagnosis, treatment options, and autopsy findings.
Primary progressive aphasia (PPA) is a rare neurodegenerative disorder characterized by an isolated and gradual dissolution of language function that progresses to dementia.1 People with PPA may have trouble with naming objects, word endings, verb tenses, conjunctions, and pronouns. The disease starts with word-finding disturbances (anomia) and progresses to impair the grammatical structure (syntax) and comprehension (semantics) of language.1
The condition begins in middle age in the form of language difficulties. Memory, visual processing, and personality remain relatively well-preserved until the advanced stages of the disease, which helps distinguish PPA from frontal lobe dementia and the typical forms of Alzheimer’s disease (AD).1,2
There are 3 classifications of PPA3:
• Progressive nonfluent aphasia (PNFA) is characterized by progressive difficulties with the production of speech.
• Semantic dementia (SD) is characterized as a disorder of word and object meaning.
• Logopenic progressive aphasia (LPA) is marked by impaired word finding and repetition difficulty.
PPA may interfere with the ability to memorize word lists or solve reasoning tasks; the patient typically has no difficulty recalling daily events or behaving with sound judgment, indicating that explicit memory, as well as social skills, remain intact at diagnosis.1 Comparatively, dementia is a syndrome of chronically progressive brain disease that impairs intellect and behavior to the point where customary activities of daily living become compromised.4
Here is a case study of a 70-year-old male who was diagnosed with PNFA in 2003. Eight years later, he had a marked decline in his condition, ultimately progressing to dementia and death.
A Case Study
A 70-year-old white male presented with a medical history of PPA, bipolar disorder, hallucinations, stuttering as a child, and hyperlipidemia. He is also a recovering alcoholic.
History. The patient was diagnosed in 2003 with PPA, but his language disturbances dated back to 1999 with the inability to write and difficulty finding the right word. He reported spelling mistakes and changes in his speech—eg, expression of language, pauses in speech, incomplete sentences, and words lost without compensation.
The patient’s wife and son sought the treatment of a geriatrician because they were concerned about the patient’s rapid decline in the past 2 to 3 weeks. His wife was not sure this was the progression of PPA or a new diagnosis. The patient did not recognize his wife or his own house. He was restless at night. He was having trouble swallowing and was choking on his food. He had poor coordination skills and it was hard for him to get food to his mouth. He was forgetting to swallow. He was not able to perform his instrumental activities of daily living and needed assistance with his activities of daily living.
Physical examination. The clinical examination was normal except for a III/VI systolic ejection murmur, an umbilical hernia that was easily reducible, and an abnormal verbal exam. He was not able to comprehend speech, his words were mumbled, and his speech was unintelligible. Therefore, he was unable to participate in extensive cognitive testing.
He was able to follow commands to take off his glasses and put them back on. He walked without assistive devices at a fast gait.
Laboratory tests. A repeated brain positron emission tomography scan in 2010 was consistent with a previous scan in 2006 that showed decreased metabolic activity in the left parietal and temporal lobes, which is highly suggestive of AD.
A MRI of the brain in 2006 showed small, scattered areas of increased signal intensity involving the white matter bilaterally, nonspecific in appearance—likely representing small vessel ischemic changes. A repeat brain MRI in 2009 showed mild cortical atrophy, particularly in the left temporal parietal region.
An electroencephalography and carotid doppler were normal. Complete blood count, comprehensive metabolic panel, vitamin B12, folate, thyroid studies, and rapid plasma reagin (RPR) levels were all normal or negative.
Diagnosis. The patient was diagnosed with dementia, likely a progression of PPA. A speech consult was obtained for his dysphagia and he was put on a pureed diet. Hospice was offered, but the family wanted to wait until the patient became worse.
Outcome of the case. The patient started to develop hallucinations and risperidone was prescribed. The family wanted his goals of care to be comfort-focused, so hospice was consulted. All medications that were not for comfort were discontinued. The patient continued to decline and died with hospice support.
An autopsy was performed. The autopsy showed high AD neuropathologic change and patchy amyloid angiopathy. There were plaques and tangles diffusely in the left and right hemisphere, but greater in the left hemisphere, which was consistent with the AD pathology. Note: Of note, 30% to 40% of PPA cases reveal AD neuropathologic changes at autopsy.5
Clinical Features
PPA is associated with atrophy of the central portion of the brain’s left hemisphere where the language center is housed. Scar tissue and abnormal proteins may also be present, and brain activity is often reduced. Research shows region-specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance.6 In patients with PPA, the perisylvian portions of the inferior frontal and temporoparietal regions (known as Broca’s and Wernicke’s areas), as well as surrounding regions of the frontal, parietal, and temporal cortex, display atrophy, EEG slowing, decreased blood flow, and decreased glucose use.4 All PPA subtypes have left hemisphere atrophy that involves components in the language network.7
Anomia, or difficulty with word finding and impaired object naming, is the single most common sign of PPA.4 Spontaneous speech becomes increasingly dysfluent. Speech errors— including simplification, circumlocution, and phonemic paraphasic mistakes—may become evident. While grammar, repetition, and comprehension are spared in the early stages, agrammatism with a progressive telegraphic-type speech pattern develops and comprehension for grammatically complex language becomes impaired. Ultimately, patients have increasing difficulties with comprehension and may become mute.
Social components, memory, visual spatial skills, and other cognitive abilities are typically preserved at the time of initial presentation. While patients usually have retained insight, they may seem unconcerned. Deficits may be restricted to expressive language function for a few to several years before a more global dementia supervenes. Some patients go on to develop behavioral alterations or symptoms of motor neuron disease or corticobasal degeneration.
PPA Versus AD
PPA should be differentiated from AD. Patients with AD seek medical attention because of forgetfulness, usually accompanied by apathy. They misplace personal objects, repeat questions, and forget recent events, but word-finding difficulty during conversations is usually not a concern. In contrast, patients with PPA seek medical attention because of the onset of word-finding difficulties, abnormal speech patterns, and prominent spelling errors.4 Language is the only area of prominent dysfunction for at least the first 2 years of PPA.4
People with PPA can become mute and may eventually lose the ability to understand written and spoken language. This generally happens within 10 years of diagnosis. As the disease progresses, other cognitive skills may become impaired as well. If this occurs, the affected person eventually will need help with activities of daily living. Depression is common in people who have PPA as well.
Risk Factors
Learning disabilities and certain gene mutations are 2 risk factors for PPA. People with learning disabilities, particularly dyslexia, are at higher risk of PPA, perhaps because both conditions involve using and understanding language. Rare gene mutations have also been linked to the disorder. If several members of one’s family have had PPA, the patient may be more likely to develop it also. However, a genetic form of PPA is extremely rare.
Diagnosis
The diagnosis of PPA is made primarily by clinical assessment. Because there is no one specific test to diagnose primary progressive aphasia, tests are done to rule-out other possible causes of symptoms.
Neuroimaging studies are required to exclude alternative pathologies and may provide supporting findings. Neuropsychological testing can be helpful in making a diagnosis and in patient management, but it is not diagnostic. Other laboratory tests, such as testing vitamin B12 and folate levels, thyroid studies, and RPR, are typically performed to exclude potential reversible contributors or causes of the cognitive impairment.
The defining feature of all PPA variants is a progressive language disorder that emerges as the principal feature of the initial clinical picture.8 Autopsies from 38 cases found that fluent/semantic and nonfluent forms of PPA have an equal likelihood (approximately 30%) of having AD pathology.9 Subsequent series from the same group based on 53 cases of PPA found AD pathology in 44% of the nonfluent but only 10% of the fluent/semantic patients.9
Studies are being done with cerebral spinal fluid (CSF) biomarkers to help classify PPA.10 CSF biomarkers may differentiate PPA with atypical AD that presents with LPA from PPA with frontotemporal lobe degeneration that presents with either PNFA or SD.10
Standardized neuropsychological tests are helpful in reaching an early diagnosis, but because most of them depend on verbal instructions, verbal responses, or verbal reasoning, reliance on these tests can lead to erroneous conclusions.4
Treatment Options
There are no medications that specifically treat PPA. Some physicians have tried Alzheimer’s medications to treat PPA, but no studies have proven the effectiveness of these medications. Experimental therapies will be available with increasing frequency in upcoming years.
Speech and language therapy, focusing primarily on efforts to compensate for eroding language skills can be helpful. If speaking and writing skills become limited, alternate communication strategies can be used. These include using cards that display specific messages or common requests, a workbook where the words can be pointed to, or laptop computers containing digitally stored words and phrases or pictures.
Hospice should be consulted when patients begin to have dysphagia, weight loss, or a functional decline. An interdisciplinary team of nurses, social workers, chaplains, physicians, pharmacists, nutritionists, family therapists, and volunteers should be involved to help emphasis quality patient care. Providing support to family members as their loved one loses the ability to communicate is essential.
PPA is a focal dementia characterized by an isolated and gradual dissolution of language function in many ways. Patients with PPA will have trouble with naming objects, word endings, verb tenses, conjunctions and pronouns. The disease starts with word-finding disturbances (anomia) and progresses to impair speech and comprehension.1 The condition begins in middle age with only language difficulties, but memory, visual processing, and personality will become affected in the advanced stages of the disease.
This case study describes a 70-year-old man who was diagnosed with PPA and it progressed to dementia and death. Differentiating the diagnosis of AD and PPA is essential through careful clinical assessment. Patients with PPA usually present with anomia, while patients with AD usually present with forgetfulness. There is no treatment at this time for PPA; studies are being done with CSF and biomarkers to help classify PPA.
An interdisciplinary team approach to care is essential in supporting the patient and family members. When the diagnosis of PPA is made, the physician should counsel the patient and family about the progressive nature of the disease, and the ultimate outcome of dementia and death.
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Jonathan Obert, MD is a gastroenterology fellow in the department of medicine at the University of Louisville, KY.
Christian Davis Furman, MD, MSPH, is a professor of geriatric and palliative medicine at the University of Louisville, KY.