Semantic Dementia Overview

Semantic Dementia:
An Overview
Ella Kondrat
December 8, 2014











Glossary:
bvFTLD behavioral variant of frontotemporal lobar degeneration
FTLD frontotemporal lobar degeneration
PPA primary progressive aphasia
SD semantic dementia
svPPA semantic variant of primary progressive aphasia

Chart A: A simplified diagram of the classification of Semantic Dementia and related diseases. (This diagram is my original work).
Introduction
Semantic dementia (SD), also known as the semantic variant of Primary Progressive Aphasia (svPPA), is a disease which results in the loss of the capacity to understand word meanings, as well as ability to name objects or remember their functions, over time (Harciarek, Sitek, & Kertesz, 2014). Patients often experience visual agnosia, or inability to recognize objects (Harciarek, Sitek, & Kertesz, 2014) and can lose the ability to identify faces (prosopagnosia).

There are two main ways that a person can acquire aphasia, which means loss of language. The more common form is usually the result of stroke, causing sudden cell death in brain areas responsible for language. Another form of aphasia is Primary Progressive Aphasia (PPA), which is due to brain degeneration, or decay in brain tissue in areas connected to language. Semantic dementia is a type of PPA (see Chart A). It is similar to other dementias such as Alzheimer's, in that they both show a decline in mental functioning over time. However, semantic dementia and the other variants of PPA differ from other dementias in that language is first affected, while memory stays intact in the earlier stages of the disease (Harciarek, Sitek, & Kertesz, 2014).

Course of the disease
Age of onset: The average SD patient first exhibits symptoms at age 60, and is diagnosed at age 64; in one study, patients as young as 40 and as old as 79 were diagnosed with SD (Hodges et al., 2009).

Earlier stages: We are lacking research on the prodromal, or early stage before clear symptom onset, stage of SD and PPA (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012). The diagnosis of PPA and its variants is often subject to a two year waiting period, which may negatively impact our ability to maximize effectiveness of interventions (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012).

The prodromal stage of SD is characterized by anomia, or impaired word finding, with spared word comprehension and object recognition (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012). In addition, SD patients may exhibit some behavioral symptoms characteristic of the behavioral variant of frontotemporal lobar degneration (bvFTLD), including behavioral disinhibition and irritability (Harciarek, Sitek, & Kertesz, 2014).

Later stages: Patients in later stages of SD may exhibit semantic jargon, in which they speak fluently and use real words, but their utterances are not comprehensible (Kertesz, Jesso, Harciarek, Blair, & McMonagle, 2010). Their speech may be garrulous, or excessively talkative, and they may have pragmatic deficits (Kertesz, Jesso, Harciarek, Blair, & McMonagle, 2010). SD patients may become mute in late stages of the disease (Harciarek, Sitek, & Kertesz, 2014).

Life expectancy can vary from 2 to more than 15 years from the date of diagnosis (Hodges et al., 2009).

Cause
There is no singular cause of semantic dementia. There is general agreement that SD results from neurodegeneration in the temporal lobes, with varying underlying pathologies (Harciarek & Kertesz, 2011; Macoir, 2014). Gorno-Tempini et al. (2011) write that there is overlap in the neuropathological causes of all variants of FTLD, as well as Alzheimer's disease, which makes it difficult to single out a single factor. In addition, inconsistency in diagnosis of the variants of PPA contributes to the lack of clarity in causation (Gorno-Tempini et al., 2011).

According to Pickering-Brown et al. (2008), there is evidence of an association between a MAPT gene variation and the presence of both the behavioral variant of FTLD and semantic dementia. However, Rohrer (2014) states that the emergence of semantic dementia is usually sporadic in nature, without a clear genetic cause. There is not a clear scientific consensus regarding the nature of genetic factors in semantic dementia.

Epidemiology
No studies have focused on the prevalence of semantic dementia. However, several studies have researched the prevalence of frontotemporal lobar degeneration (FTLD), of which semantic dementia is a subtype (see Chart A). Knopman & Roberts (2011) estimate the prevalence of FTLD in the United States to be 20,000 to 30,000 individuals; the prevalence of semantic dementia is lower than the prevalence of FTLD, but the actual number is not known. Knopman and Roberts (2011) attribute the uncertainty in these numbers to lack of accuracy in clinical diagnosis of the FTLD variants.
A substantial number of patients receive a diagnosis of FTLD before the age of 65, while FTLD is most commonly seen in patients between ages 66 and 75 (Borroni et al., 2010). One study found that 0.022% of a population between ages 45 and 65 had an FTLD diagnosis, compared with 0.078% in the 66-75 age range, and 0.054% over age 75 (Borroni et al., 2010). Another study found a prevalence of 0.081% for ages 45-64 (Ratnavalli, Brayne, Dawson, & Hodges, 2002).

Pathophysiology
Semantic dementia is the result of physical changes in the brain, which can be observed using magnetic resonance imaging (MRI) or positron emission tomography (PET) scans (Irish, Addis, Hodges & Piguet, 2012; Diehl et al., 2004). Over time, the normally plump gyri of the brain atrophy, taking on a knife-like appearance (Galasko & Marder, 2002). Patients with semantic dementia often exhibit TAR DNA-binding protein 43 positive ubiquinitopathy (Hodges et al., 2009; Harciarek, Sitek, & Kertesz, 2014).

In a typical picture of SD, the left anterior temporal lobe shows the most widespread damage, while the right temporal lobe is affected to a much lesser extent (Diehl, 2004; Irish, Addis, Hodges & Piguet, 2012). In later stages, the lateral and ventral areas of the temporal lobes can be affected, including the fusiform gyrus (Harciarek & Kertesz, 2011). The fusiform gyrus contains a facial recognition area (Kanwisher, McDermott & Chun, 1997), damage to which can lead to prosopagnosia, or inability to recognize faces (Gainotti, & Marra, 2010).

This picture shows the brain areas most affected by the three variants of PPA (Harciarek & Kertesz, 2011).


Fusiform gyrus is shown in yellow (Fusiform gyrus, n.d.).

The colored areas show "decreased grey matter intensity."
Yellow = semantic dementia
Pink = Alzheimer's disease
(Irish, Addis, Hodges, & Piguet, 2012).

Diagnostic Signs/Symptoms
It can be difficult for clinicians to distinguish semantic dementia from the different variants of FTLD (see Chart A), especially in early stages of the disease (Galasko & Marder, 2002; Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012).

Gorno-Tempini et al. (2011) define semantic dementia as being characterized by impaired abilities in word retrieval, semantic association, and single word comprehension, while retaining syntactic comprehension and speech fluency.

The diagnostic process begins with a diagnosis of primary progressive aphasia (PPA) (Gorno-Tempini et al., 2011). To be classified as PPA, language must be the primary area affected in the early stages of the disease, and it must be the primary contributor to difficulties in activities of daily living (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012). Stroke, tumor, psychiatric issues, and other non-neurodegenerative causes are ruled out (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012). Episodic and visual memory, as well as visuoperception, must be spared (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012).

Once the PPA diagnosis is established, the patient is classified into one of three variants of PPA: the semantic, nonfluent, or logopenic variant (Gorno-Tempini et al., 2011). The two\
primary features of the semantic variant of PPA (also known as semantic dementia) are impaired confrontation naming and impaired single-word comprehension (Gorno-Tempini et al., 2011). Confrontation naming is tested by showing the patient a picture of an object and asking him or her to name it (Gorno-Tempini et al., 2011). Single-word comprehension can be tested by saying a word and having the patient pick the picture that matches the word (Gorno-Tempini et al., 2011).

In addition to the two primary features of SD, three of four secondary features are required to occur in an SD patient: impaired object knowledge, surface dyslexia or dysgraphia, spared repetition, and spared grammar (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012). Impaired object knowledge is usually seen with less familiar objects (Mesulam, Wieneke, Thompson, Rogalski, & Weintraub, 2012); for example, "mongoose" may be lost before "cat." Surface dyslexia and dysgraphia can cause regularization reading and spelling errors which are characteristic of SD; for example, an irregularly spelled word such as debt is spelled as "det," or the "b" in debt is pronounced when the word is read aloud (Shim, 2012).

Medical Treatment

Several studies have evaluated the effects of drugs (namely: Memantine, Galantamine, and Rivastigmine) on word retrieval abilities in patients with SD and/or PPA, but have not found significant improvement (Boxer et al., 2013; Kertesz et al., 2008; Kowa, Seki, Yamamoto, Kanda, & Toda, 2012). In the case of Memantine, performance actually dropped (Boxer et al., 2013).

Transcranial magnetic stimulation (TMS) has been shown to help improve language in patients with Alzheimer's disease, stroke-induced aphasia, PPA and logopenic variant of PPA (Cotelli et al., 2006; Mottaghy et al., 1999; Trebbastoni, Raccah, deLena, Zangen, & Inghilleri, 2013). However, its effects have not been studied specifically on SD patients, so it is unknown whether TMS would be helpful for SD.

Behavioral Therapy
Kindell, Sage, Keady, & Wilkinson (2013) found that the adaptive strategy of acting out, or enactment, using paralinguistic and non-vocal communication, was effective in expanding one individual's ability to communicate meaningfully in the absence of adequate word retrieval abilities.

Rogalski and Edmonds (2008) developed a technique called Attentive Reading and Constrained Summarization, which encourages increased attention and intentional use of language on a discourse level, rather than the single word level that most studies have investigated. This technique is intended to exercise brain pathways to help maintain access to precise word meanings. This case study found that the patient maintained gains over two months, which is unusual in studies of primary progressive aphasia.

Jokel and Anderson (2012) found that errorless learning, in which the client is prevented from incorrectly identifying a stimulus during therapy, increased the ability of persons with semantic dementia to name objects, but did not affect auditory comprehension or recognition. In addition, the study found that words that the patients understood but could not name before treatment, were more likely than words not understood before treatment, to be understood one month after treatment.



Additional resources
WEBSITES
Association for Frontotemporal Degeneration
http://www.theaftd.org/

National Aphasia Association:
Information for people with aphasia, their caregivers, and helping professionals.
http://www.aphasia.org/

National Aphasia Association Affiliates:
A searchable database of aphasia groups, institutions, and resources.
http://www.aphasia.org/naa-network3

BOOKS
What If It's Not Alzheimer's?: A Caregiver's Guide To Dementia (3rd Edition)
http://www.amazon.com/What-Its-Not-Alzheimers-Caregivers/dp/161614968X/ref=pd_sim_b_5?ie=UTF8&refRID=1YDDNCASYAXR44ZHB0X5

Creating Moments of Joy for the Person with Alzheimer's or Dementia: A Journal for Caregivers, Fourth Edition
http://www.amazon.com/Creating-Moments-Person-Alzheimers-Dementia/dp/1557534624/ref=pd_sim_b_1?ie=UTF8&refRID=0WX5NZBH817D4E2HSZJP

CONFERENCE
2013 Frontotemporal Degeneration/ Primary Progressive Aphasia (FTD/PPA) Annual Conference
http://www.brain.northwestern.edu/about/events/ftdppa.html





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