Non-right handed primary progressive apraxia of speech

Abstract

In recent years a large and growing body of research has greatly advanced our understanding of primary progressive apraxia of speech. Handedness has emerged as one potential marker of selective vulnerability in degenerative diseases. This study evaluated the clinical and imaging findings in non-right handed compared to right handed participants in a prospective cohort diagnosed with primary progressive apraxia of speech. A total of 30 participants were included. Compared to the expected rate in the population, there was a higher prevalence of non-right handedness among those with primary progressive apraxia of speech (6/30, 20%). Small group numbers meant that these results did not reach statistical significance, although the effect sizes were moderate-to-large. There were no clinical differences between right handed and non-right handed participants. Bilateral hypometabolism was seen in primary progressive apraxia of speech compared to controls, with non-right handed participants showing more right hemispheric involvement. This is the first report of a higher rate of non-right handedness in participants with isolated apraxia of speech, which may point to an increased vulnerability for developing this disorder among non-right handed participants. This challenges prior hypotheses about a relative protective effect of non-right handedness for tau-related neurodegeneration. We discuss potential avenues for future research to investigate the relationship between handedness and motor disorders more generally.

Keywords: FDG-PET imaging; Handedness; Primary progressive aphasia; Progressive apraxia of speech.

Figure 1. Three-dimensional brain renderings showing FDG-PET hypometabolism in right-handed PPAOS

(A) Compared to controls, RH PPAOS participants had focal hypometabolism most marked in the posterior medial frontal lobe in the area of the SMA bilaterally, as well as bilateral precentral gyri, left greater than right. Results are shown corrected for multiple comparisons using FDR at p < 0.05. (B) Compared to nRH PPAOS participants, RH participants had focal of hypometabolism of the right fusiform and inferior temporal gyrus (results shown uncorrected for multiple comparisons, at p = 0.001). Effect size (Cohen’s d) and -log 10 p-value maps are also shown. An effect size of 0.5–0.8 is commonly interpreted as ‘moderate’ whereas values above 0.8 are considered ‘large’. A -log10 p-value of 3 corresponds to 0.001, while 2 and 4 correspond to 0.01 and 0.0001, respectively. Three dimensional displays of the MCALT atlas used here were created with Surf Ice (https://www.nitrc.org/projects/surfice/). Abbreviations: L = left, PPAOS = primary progressive apraxia of speech, R = right

Figure 2. Three-dimensional brain renderings showing FDG-PET hypometabolism in non-right-handed PPAOS

(A) Compared to controls, nRH PPAOS participants had focal hypometabolism most marked in the right precentral and inferior frontal gyri, with smaller areas involving the SMA bilaterally. Results are shown corrected for multiple comparisons using FDR at p < 0.05. (B) Compared to RH PPAOS participants, there was a small focus in the right superior frontal gyrus that was relatively hypometabolic in nRH participants. Effect size (Cohen’s d) and -log 10 p-value maps are also shown. Both suggest more widespread precentral/premotor involvement that may have failed to reach significance because of the small numbers despite large effect sizes. An effect size of 0.5–0.8 is commonly interpreted as ‘moderate’ whereas values above 0.8 are considered ‘large’. A -log10 p-value of 3 corresponds to 0.001, while 2 and 4 correspond to 0.01 and 0.0001, respectively. Three dimensional displays of the MCALT atlas used here were created with Surf Ice (https://www.nitrc.org/projects/surfice/). Abbreviations: L = left, PPAOS = primary progressive apraxia of speech, R = right

Figure 3. FDG-PET statistical stereotactic surface projection maps of nRH participants

See text and Table 3 for details.