The Association Between Distinct Frontal Brain Volumes and Behavioral Symptoms in Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia

Abstract

Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer's disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = −0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = −0.30, p = 0.002), medial frontal cortex (β = −0.30, p = 0.002), superior frontal gyrus (β = −0.28, p = 0.003), inferior frontal gyrus (β = −0.28, p = 0.005) and subcallosal area (β = −0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = −0.30, p = 0.002) and inferior frontal gyrus (β = −0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = −0.29, p = 0.005) and the subcallosal area (β = −0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.

Multivariate neuroanatomical correlates of behavioral and psychological symptoms in dementia and the moderating role of education

“…Consistent with previous studies, we confirmed that the lateral and orbital regions of the prefrontal cortex may play a critical role in withstanding late-life socioemotional impairment ( Cajanus et al, 2019 , Hu et al, 2015 , Peters et al, 2006 ). Specifically, the left inferior gyrus is a critical region in reappraising and regulating negative emotions while attenuating excessive amygdala activity ( Berna et al, 2010 , Goldin et al, 2008 ).…”

“…The entorhinal cortex and hippocampal structures typically undergo prominent atrophy in patients with AD; therefore, the current analysis may have captured the major source of global AD pathology. It should be noted that previous studies did not affirm the role of the amygdala structure in NPS, possibly due to insufficient sample size or exclusion from the analysis target; however, our study illustrated that the amygdala-centered multivariate pattern was a significant correlate even after adjusting global dementia severity ( Cajanus et al, 2019 , Horinek et al, 2006 , Poulin et al, 2011 ).…”

“…It consists of 12 separate items assessing neuropsychiatric disturbances, including delusion, hallucination, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, and aberrant motor behavior ( Table 2 ). In this study, eating abnormalities and nighttime behavior symptoms were excluded from the analyses because they are not part of the core NPI questionnaire ( Cajanus et al, 2019 ). The NPI items coded symptoms as four levels: absent (0, no symptoms), mild (1, noticeable, but not a significant change), moderate (2, significant, but not a dramatic change), and severe (3, very marked or prominent; a dramatic change).…”

The impact of tinnitus on working memory capacity

“…Hamani et al 2011). Atrophy in the subcallosal region is however also significantly associated with behavioural symptoms of neurodegenerative diseases such as mild cognitive impairment, Alzheimer's disease and behavioural variant frontotemporal dementia irrespective of disease aetiology (Cajanus et al 2019), indicating that the subcallosal region could also play a role for cognitive processes.…”

4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

“…The frontal cortex responsible for executive and higher cognitive functions, such as cognitive flexibility, is one of the most affected brain regions in the AD brain [27,28]. Interestingly, more significant oxidative damage is observed in the frontal cortex than other brain regions in AD brain [9,10].…”