TABLE 3.
Behavioral changes in ALS.
| Authors/year | N | Type | Outcomes measures | Main findings |
| Andrews et al., 2017a | 40 pts / 40CG and 27 NC & relatives | CS | Behavioral changes: CBI-R CG burden | Pts: disturbance on everyday skills, self-care, and sleep, mood and motivation. CG burden: pts’ skills, motivation and memory |
| Bock et al., 2016 | 86 pts | CS | Cognitive-Behavioral Screen Patient QoL CG burden Disease stage | Cognitive impairment: 62%; Behavioral impairment: 37%; FTD: 5% Severity of deficits not associated with patient QoL; predicts higher CG burden. Self-reported QoL lower in pts with depressive symptoms and more advanced disease |
| Bock et al., 2017 | 49 pts BL & 7 mo | LS | Assessment of cognitive-behavioral function using the ALS-CBS | Cognitive status: no change over time; Pts initially classified as behaviorally normal show increased behavioral problems over time |
| Burke et al., 2017 | 317 pts / 66 NC | CS | Behavioral changes: BBI Cognitive assessment, Impact on survival | Behavioral changes: none, 57%; mild to moderate: 30%; severe (FTD) : 13% Behavioral changes predicted by social cognitive performances. No impact on survival |
| Caga et al., 2018 | 60 pts | Cs | Impact of apathy (AES) on QoL (PWI) | Apathy: 30 %. Pts with apathy have poorer overall QoL |
| Consonni et al., 2013 | 23 pts, 11 Lower MND, 39 NC | CS | Cognitive and behavioral assessment | Executive dysfunction: 30% of ALS pts disorganization and mental rigidity: 20% Dementia:13%. No correlation between cognitive and behavioral changes and clinical features |
| Crockford et al., 2018 | 161 pts, 80 NC | CS | Pts: ECAS; Disease stage : the King’s Clinical Staging System CG behavioral interview | Behavioral impairment : 40% (firstly apathy). Higher number of behavioral features found across advancing stages. |
| Femiano et al., 2018 | 22 pts / 19 NC | CS | Apathy: AES, FrSBe, Global cognitive assessment, Brain imaging: DTI | No behavioral and cognitive impairment. Apathy inversely correlated to fractional anisotropy (FA) in several WM areas |
| Floeter et al., 2017 | 34 pts at BL, 6, 12, 18 mo | LS | Cognitive and behavioral manifestation in carriers of the mutation C9orf72: letter fluency and FBI-ALS | Symptomatic carriers decline at each evaluation on cognitive and behavioral functioning |
| Gibbons et al., 2008 | 16 pts | CS | The Manchester FTD Behavioral Interview of informants | Behavioral changes: 87%; FTD:8% Behavioral changes associated to bulbar palsy, but not to disease duration |
| Kasper et al., 2015 | 98 pts / 70 NC | CS | Executive cognitive, Executive behavior | 70% of ci pts have executive dysfunction (initiation and shifting). Dominant bi is apathy |
| Grossman et al., 2007 | 45 pts | CS | FrSBe, Verbal fluency and DKEFS BDI | Changes in apathy scores. Apathy correlates with verbal fluency but not with depressive symptoms |
| Lillo et al., 2011 | 92 pts | CS | Self-report measures of motor function and mood CBI-R in 81 pts | Reduced motivation: 80 % (apathy in 41 %). Stereotypical and abnormal motor behaviors: 20 %; FTD: 11 % |
| Lillo et al., 2012 | 140 CG | CS | CG burden: Zarit Burden Interview CG mood: DASS, Pts behavioral changes: CBI-R | Behavioral changes in 10-40% of pts; Depression, anxiety in 20% of CG; high burden in 48% of CG; Strongest predictor of high CG burden = pts’ abnormal behavior |
| Marconi et al., 2012 | 10 pts with tracheostomy and their CG | CS | Anxiety and depression with the HADS Personality of CG using the Big Five Questionnaire (BFQ) | A trend of aggression and high level of obsessiveness in ALS pts. High levels of anxiety in both pts and CG. Higher scores in the dimension of conscientiousness in CG |
| Mioshi et al., 2014 | 219 pts 20 pts at 6m | Co LS | MiND-B ALS-FRS | Neuropsychiatric symptoms appear before classic motor features. Not associated with survival. No significant change at 6 mo |
| Murphy J. M. et al., 2007 | 23 pts | CS | Neuropsychological and neurobehavioral assessment : ALS-CBS | No impairment: 11 pts; behavioral changes: 4; FTD: 5;other :3 (Alzheimer : 1) |
| Ohta et al., 2017 | 57 ALS, 5 ALS-FTD, 12 FTD, 35 NC | CS | Cognitive, behavioral, affective and activities of daily living assessment | FAB and MoCA useful to assess frontal cognitive impairments. ALS-FTD-Q useful to detect mild behavioral and affective disturbances. |
| Poletti et al., 2018 | 168 pts at BL 48 after 6 mo 18 after 12 mo 5 after 24 mo | LS | ECAS, FAB and MoCA BDI and STAI/Y | No cognitive deterioration across follow-ups. improvement of some ECAS scores over time due to possible practice effects. Apathy/Inertia = most common behavioral symptom, but no worsening over time. |
| Rabkin et al., 2016 | 247 pts | CS | Cognition-behavior : CBS Psychological : PHQ | 40 % ci, 9% bi, 18% ci and bi, 12 % Major or minor depression; 12% Bi associated with depression |
| Radakovic et al., 2017 | 30 ALS pts / 29 NC | CS | Apathy subtypes with the self- and informant/carer-rated DAS, Cognition: ECAS Comprehensive neuropsychological battery | Increased Initiation apathy was the only significantly elevated subtype in ALS. Initiation apathy associated with verbal fluency deficit, and Emotional apathy, with emotional recognition deficits |
| Terada et al., 2011 | 24 pts | CS | Behavioral changes: the FrSBe, ALSFRS respiratory function, arterial blood gases | No correlation between FrSBe scores and ALSFRS, respiratory function, or arterial blood gases. Most frequent behavioral change: apathy |
| Tremolizzo et al., 2016 | 84 pts & CG | CS | Pts: ALSCBS-ci and –bi, FAB and BDI CG: BDI and CGBI. | CG burden correlates with pts behavioral but not cognitive changes. CG Burden correlates to CG depression |
| Unglik et al., 2018 | 152 pts | CS | EPN-31 (emotional feeling); HADS, The Marin’s apathy evaluation scale Cognitive assessment: ALS-CBS scale. | Apathy: 42 %; related to negative emotions and negatively correlated to cognitive functioning and survival |
| Witgert et al., 2010 | 225 pts | CS | FrSBe, Comprehensive neuropsychological evaluation | Changes in the total score: 24.4% (firstly apathy). Cognitively impaired pts have worse total and apathy scores. Behavioral changes in 16 % of cognitively intact pts |
| Woolley et al., 2010 | 17 ALS 4 ALS-FTD | CS | Behavioral changes: FrSBe Pts’ awareness of their behavioral changes | Not demented ALS pts have normal insight compared to FTD-ALS pts who have behavioral changes and no insight |
| Woolley et al., 2011 | 24 pts; 24 NC | CS | Apathy Brain imaging: DTI | Apathy correlated to FA in right anterior cingulum; not correlated with disease duration or respiratory dysfunction |
| Woolley et al., 2018 | 294 at BL 134 at 12 mo | LS | ALS-CBS, Verbal Fluency Index, Controlled Oral Word Association Test and FBI-ALS | No cognitive decline over time; Behavioral change, with increased disinhibition among patients with abnormal BL behavioral scores; BL behavioral problems associated with advanced, rapidly progressive disease |
AES, Apathy Evaluation Scale; ALS-FRS, ALS Functional Rating Scale; BBI, Beaumont Behavioral Inventory;CBI, Cambridge Behavioral Inventory; CGBI, Caregiver Burden Inventory; DAS, Dimensional Apathy Scale; DASS, Depression, Anxiety and Stress Scale; DKEFS, Delis-Kaplan Executive Functioning Scales; EPN-31, Positive and Negative Emotionality Scale; HADS, Hospital Anxiety and Depression Scale; MND, Motor Neuron Disease; MoCA, Montreal Cognitive Assessment; PWI, Personal Wellbeing Index; WM, White Matter. For more please refer to previous tables.