On January 4, 2011, the President of the United States signed the National Alzheimer’s Project Act (NAPA) to benefit Alzheimer’s and related disorders. The act charges the Secretary of Health and Human Services to coordinate research, to accelerate treatments to prevent, reverse, or halt Alzheimer’s, to coordinate care and treatment of Alzheimer’s patients, including ethnic and racial populations experiencing higher risk, and, finally to coordinate with international bodies to fight the disease. ¹ The act is welcome news to all who care for those affected by Alzheimer’s and related dementias, as well as to scientists who strive to find causes and treatments for these disorders.

The purposes of this chapter are to review the diagnostic criteria of the major types of neurodegenerative dementia, to contrast their phenotypes, and to identify diagnostic and intervention approaches useful to speech-language pathologists (SLPs). To this end, new diagnostic criteria articulated by National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines (NIA-AA workgroup) are highlighted. ^{2,​ 3,​ 4,​ 5} Because this chapter consolidates material from two chapters in the second edition of Johnson and Jacobson’s Medical Speech-Language Pathology (2007), readers are referred to Horner et al ⁶ and Norman et al ⁷ in the earlier volume for comprehensive descriptive and bibliographic detail.

6.2 Diagnostic Features of Neurodegenerative and Other Dementias

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition text8, uses the term neurocognitive disorders (NCDs) as the umbrella for disorders such as dementia, delirium, amnestic and other cognitive disorders defined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition ⁹. A major NCD is one in which there is “evidence of a significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition); . . . the cognitive deficits interfere with independence in everyday activities; . . . the cognitive deficits do not occur exclusively in the context of delirium; . . . [and], the cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia)” (DSM-5, pp. 602-603). A mild NCD is similar but cognitive decline is modest; and cognitive deficits do not interfere with independence “but greater effort, compensatory strategies, or accommodation may be required” (DSM-5, p. 605). Although the term dementia is retained in DSM-5 because of its customary usage by clinicians, DSM-5 notes that neurocognitive disorder encompasses not only the neurodegenerative dementias affecting older adults but also those NCDs manifesting in younger individuals (e.g., after traumatic brain injury) as well as those NCDs affecting single cognitive domains (e.g., amnestic disorder) (DSM-5, p. 591).

The Einstein Aging Study examined 1,944 community-dwelling adults, age 70 or older, for presence of Alzheimer dementia (AD), amnestic mild cognitive impairment (aMCI), and nonamnestic mild cognitive impairment (naMCI). Overall dementia incidence was 2.9/100 person-years (2.3/100 for AD; 3.8 for aMCI; 3.9 for naMCI). Overall dementia prevalence was 6.5% (4.9% for AD; 11.6% for aMCI; 9.9% for naMCI). With the exception of naMCI, rates increased significantly with age. ¹² According to the Alzheimer’s Association, ¹³ an estimated 5.4 million Americans had Alzheimer’s disease in 2012; this represents 13% of individuals over age 65 and 45% of those over age 85. According to the National Institute on Aging, ¹⁰ “the number of people with Alzheimer’s doubles for every 5-year interval past age 65. And the ranks of the very elderly, those 85 and older and at the highest risk for Alzheimer’s, are expected to triple by 2050.”

The various NCDs are clinical syndromes defined by prominent clinical signs, age of onset, and pattern of progression. In DSM-5, NCDs are also subtyped base don “known or presumed etiological/pathological entity or entities” (p. 606), e.g., an Alzheimer’s disease genetic mutation or family history (p. 611). History and clinical testing are centerpieces of the examination, supplemented by biomarker techniques (fluid analyses, neuroimaging, and genetic testing) and longitudinal follow-up. A definitive diagnosis of the underlying disease is often not possible until autopsy, when neuropathologists examine brain cells using histopathologic techniques. Thus, clinicians differentiate the dementias on the basis of clinical signs and biomarkers; neuroradiologists, on the basis of static images of brain structure as well as dynamic images of brain metabolism; and neuropathologists, on the basis of postmortem analysis of brain tissue. In contrast, geneticists, microbiologists, and epidemiologists seek to understand the origins of dementia. Epidemiologic studies suggest that one’s susceptibility to disease is multifactorial, reflecting interactions among genetic, environmental, experiential, nutritional, and other factors. In short, clinical studies are concerned with patterns of behavior and cognition associated with dementing illnesses; neuroradiologic studies, with structural and functional abnormalities of brain tissue, both at cortical and subcortical sites; postmortem studies, with actual pathologic changes in the brain; and, biologic, genetic, and epidemiologic studies, with the pathogenesis (the origins) of the underlying disease. ¹¹

6.2.1 Differentiating All-Cause Dementia from Alzheimer Dementia (AD) and Mild Cognitive Impairment

Refined diagnostic guidelines were promulgated in 2011 by the NIA-AA workgroups on diagnostic guidelines for AD. ^{2,​ 3,​ 4,​ 5} The NIA-AA workgroup distinguished a preclinical phase (asymptomatic patients with abnormal metabolic or structural biomarkers) from a clinical phase of AD (signs of dementia with or without biomarker confirmation). “Biomarkers are parameters (physiological, biochemical, anatomic) that can be measured in vivo and that reflect specific features of disease-related pathophysiological processes,” ³ such as abnormal levels of beta-amyloid protein in cerebrospinal fluid (CSF), or hypometabolism during positron emission tomography (PET), or atrophy on magnetic resonance imaging (MRI). ⁵ The contributing scientists examined the relationship of clinical and biomarker signs. They reported (1) patients might be asymptomatic and be free of extensive AD biomarker pathology, or patients might present either typical or atypical clinical signs of AD in the presence of AD pathology; (2) amyloid biomarkers are often abnormal as long as 10 to 20 years before clinical signs appear; and (3) signs of neurodegeneration (particularly synapse loss) appear later and are more closely tied to cognitive impairment than amyloid protein disturbance. ³

Two comprehensive and useful documents are the National Institute on Aging’s “2010 Alzheimer’s Disease Progress Report” ¹⁰ and the Alzheimer’s Association’s “2012 Alzheimer’s Disease Facts and Figures” report. ¹³ ▶ Table 6.1 summarizes differences among mild cognitive impairment (MCI), all-cause dementia, and probable Alzheimer dementia (AD). ▶ Table 6.2 summarizes the differential clinical features of the major neurodegenerative dementias: Alzheimer dementia, vascular dementia, Lewy body dementia, and frontotemporal lobar dementia, drawing from the literature to summarize the major features of each category relative to onset and course, subtypes, cognitive profile, communication, associated behavior, physical signs, genetics, imaging, and definitive diagnosis.

Alzheimer Dementia (AD)

AD is defined clinically by its insidious, progressive course of cognitive disability; biologically, by in vivo biomarkers (of amyloid metabolism or imaging abnormalities, such as atrophy); neuropathologically (at autopsy), by an abundance of plaques and tangles; and genetically by abnormalities is some patients. The dementia is heterogeneous, ¹⁴ its underlying cause is illusive, and its cure is as yet undiscovered. ^{15,​ 16,​ 17}

Vascular Dementia (VaD)

The second most prevalent type of dementia, VaD is typically caused by white matter ischemic necrosis with neuronal loss (leukencephalopathy) and multiple brain infarcts, including lacunar infarcts. ^{18,​ 19,​ 20,​ 21} “The clinical patterns of VaD differ, depending on the vessels involved (large versus small vessel), location of vascular lesions and the stages of disease.” ²² To the extent that cerebrovascular disease can be identified and treated, VaD is unique among the dementias, because it is preventable. ²³ Although cerebrovascular disease co-occurs with, or predisposes individuals to, AD, ²⁴ VaD often occurs in the absence of AD pathology. ²⁰

According to the NIA-AA workgroup, the diagnosis of probable AD dementia should not be applied when there is evidence of (a) substantial concomitant cerebrovascular disease, defined by a history of a stroke temporally related to the onset or worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white matter hyperintensity burden; or (b) core features of dementia with Lewy bodies other than dementia itself; or (c) prominent features of behavioral variant frontotemporal dementia; or (d) prominent features of semantic variant primary progressive aphasia; or (e) evidence for another concurrent, active neurological disease, or a non-neurological medical comorbidity or use of medication that could have a substantial effect on cognition. ⁴

Lewy Body Dementia (LBD)

Lewy body disease with dementia (LBD) is one of the most challenging of the neurodegenerative dementias. Three Lewy body syndromes have been described: movement disorder, autonomic failure, and dementia. ^{25,​ 26,​ 27} The diagnostic challenge arises not only because of the variant syndromes, but also because the presence of Lewy bodies is not exclusive to LBD (Lewy bodies can coexist with the plaques and tangles of Alzheimer’s disease), and because both cortical and subcortical sites are affected. ²⁸ In LBD, fluctuating attention is typical and is characterized by marked shifts in alertness (within or between sessions), daytime drowsiness in some, and transient confusion on waking. In addition, probable LBD patients have recurrent, detailed, and persistent hallucinations, including animate and inanimate figures and scenes. Visual hallucinations appear “to be the only psychotic symptom that reliably discriminates LBD from AD or VaD.” ²⁹ In summary, LBD is characterized by cortical and subcortical disease, has less medial temporal lobe involvement than AD, shares common neuropathological and neurogenetic features with Parkinson’s disease, and is distinguished from the other neurodegenerative diseases by fluctuating attention, visual hallucinations, and parkinsonism.

Frontotemporal Lobar Dementia (FTLD)

Contemporary researchers now prefer the term frontotemporal lobe dementia (FTLD) for what was formerly thought of as a singular entity known as Pick’s dementia. The common thread among the different FTLD syndromes is focal atrophy, implying neuronal loss in particular cortical regions. Several subtypes are recognized: “behavioral or frontal-variant frontotemporal dementia (fv-FTD; sometimes simply called FTD); the temporal variant (tv-FTD), or semantic dementia (SD); and a left frontal and insular predominant degeneration called progressive non-fluent aphasia (PNFA).” ³⁰ Hodges ³¹ emphasized that semantic dementia implies not only anomia but also a breakdown in semantic memory, that is, problems with not only word-finding, but also word comprehension and object recognition.

AD and the FTLD variants resulting from lobar atrophy demonstrate distinctive profiles of cognitive impairment, and the FTLD syndromes are distinguishable from AD, both behaviorally ³² and neuroradiologically. ³³ As Perry and Hodges ³⁴ pointed out, the emergence of pharmacologic treatments for both memory and behavioral problems of FTLD mandates careful differential diagnosis. In summary, FTLD is an umbrella term referring to a host of clinical syndromes that share the common feature of focal cortical atrophy. There are three variants—frontal, temporal, and nonfluent aphasia—that reflect the location of the atrophy, not the underlying neuropathological disease. The variants are particularly important to speech-language pathologists because they present with executive disability, semantic impairments, and Broca’s-like aphasia, respectively.

Mild Cognitive Impairment

To introduce the topic of mild cognitive impairment (MCI), Petersen et al ³⁵ explained that “the use of research criteria for the classification of dementia identifies three groups of subjects: those who are demented, those who are not demented, and individuals who cannot be classified because they have a cognitive…impairment but do not meet criteria for dementia.” The last group—those who have a measurable cognitive deficit but do not have dementia—are referred to as having MCI. Initially MCI was conceived of as being an isolated memory impairment (amnestic MCI), but a working group on MCI more recently identified other affected cognitive areas, so-called nonamnestic MCI. ^{2,​ 36,​ 37} Individuals have MCI if they (1) do not meet the criteria for dementia; (2) demonstrate abnormal cognition (as compared to age- and education-matched peers) by subjective report and corroborated by a family member, or measured objectively; and (3) preserve independence in daily functional activities. ^{2,​ 37}

A major focus of research is whether MCI will ultimately evolve to AD. According to Albert et al, ² MCI is at risk for conversion to AD if there is an abnormality of the gene for apolipoprotein E (APOE). Risk for conversion is also present if CSF analysis shows low levels of the beta-amyloid protein, and/or if the tau protein is elevated in CSF; beta-amyloid and tau are biomarkers for amyloid plaques, neurofibrillary tangles, and loss of neuronal connections and cell death. ^{2,​ 10} For a vivid display of these changes, see “Inside the Brain: Unraveling the Mystery of Alzheimer’s Disease,” a four-minute video available on the National Institute on Aging Website. ³⁸ In contrast, Sattler et al ³⁹ reported several protective factors that independently influenced late-onset AD in patients with MCI, namely, participation in cognitive leisure activities (CLA), higher education, and higher socioeconomic status (SES). As compared to matched subjects followed over a 12-year period, these individuals reduced their risk for AD by 62% (CLA), 85% (education), and 69% (SES), suggesting the importance of a lifelong pattern of establishing and maintaining “cognitive reserve.” ³⁹

Primary Progressive Aphasia

A clinical entity of particular interest to SLPs is primary progressive aphasia (PPA). The syndrome is characterized, initially, by isolated language disturbance that slowly progresses and may or may not lead to global deterioration of cognitive abilities. Following Mesulam’s ⁴⁰ fascinating case study of “slowly progressive aphasia without generalized dementia,” many cases have been published (see Horner et al ⁶ for a review of this literature). Agreement about the definition and subtypes of PPA, however, did not occur until 2011. ⁴¹ Despite its heterogeneous causes (overlapping with FTLD and AD), most cases of PPA commonly present as frontotemporal lobe degeneration. Language disorder is the prominent sign of PPA and is the reason for impaired daily functioning; impaired functioning is not attributable to memory disorders or visuospatial impairments; and PPA is not attributable to other medical disorders or psychiatric illness. ⁴¹ The working group identified three variants of PPA: the nonfluent/agrammatic variant (apraxia of speech may also be present); the semantic variant; and the logopenic variant (in which word-retrieval and sentence-repetition deficits are prominent) (see Gorno-Tempini et al ⁴¹ for detail).

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