The relationship between frontotemporal dementias (FTDs) and amyotrophic lateral sclerosis (ALS) is well established and is believed to be more pronounced in those with bulbar onset ALS (B-ALS). This study compared cognitive and behavioral symptoms among persons with B-ALS to those of individuals with nonbulbar phenotypes (NB-ALS).

Outpatient clinic data collected during an initial neuropsychology consultation at an ALS interdisciplinary clinic in an academic medical center was retroactively analyzed. All individuals were diagnosed with ALS by neurologists specializing in movement and neuromuscular disorders based on results of neurological/motor examination, electromyographies, and (when available) genotypic data. Total scores on the short form of the Montreal Cognitive Assessment (MoCA-SF) and scores on the ALS Cognitive Behavioral Screen (ALS-CBS) and ALS CBS Caregiver questionnaire were of focus. 22 B-ALS and 44 NB-ALS individuals were compared on said measures using univariate analyses while controlling for ALS symptoms duration.

B-ALS individuals scored significantly lower on the MoCA-SF (F(2)=3.15, p=0.05, n2=0.13) and the tracking subscale of the ALS-CBS (F(2)=3.50, p=0.04, n2=0.17). The groups were not significantly different on other ALS-CBS measures, including caregiver-rated behavior questionnaire.

Consistent with previous research, this study found lower total scores on a brief screener of global cognition and tasks of tracking requiring cognitive control in those with B-ALS relative to NB-ALS individuals. Interestingly, despite behavioral variant being the most prevalent FTD phenotype, the groups did not differ significantly in terms of caregiver-rated behavioral changes. It is hypothesized that the absence of these differences could reflect effects of gradual loss of speech and functionality that secondarily limit caregivers' abilities to observe behavioral changes concerning for possible behavioral variant FTD. That said this could reflect limitations of the sample and/or study design, and further exploration is therefore needed. Recommendations for future studies of neuropsychological/behavioral variables in B-ALS as well as development of more targeted instruments for use in this population are discussed.

Parkinson’s disease (PD) is associated with metabolic disorders such as insulin resistance. Pharmacological intervention used to treat insulin resistance, like GLP-1 agonists, may have auspicious results in the treatment for PD. The objective of this clinical trial was to assess the therapeutic effect of liraglutide on non-motor symptoms, such as, but not limited to, cognitive function and emotional well-being, and quality of life for individuals with PD.

In a single-center, randomized, double-blind, placebo-controlled trial, PD patients self-administered liraglutide injections once-daily (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptom scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2). Secondary outcomes included quality of life scores (Parkinson Disease Questionnaire, PDQ-39) and other neuropsychological tests, including Delis-Kaplan Executive Function System (DKEFS), Geriatric Depression Scale (GDS), and Parkinson’s Anxiety Scale (PAS) scores.

Sixty-three subjects were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Mean age in years was 63.5 (9.8) and 64.2 (6.4) for liraglutide and placebo cohorts, respectively (p=0.78), and mean age at symptom onset was 58.9 (10.5) and 59.3 (7.5) for liraglutide and placebo cohorts, respectively (p=0.86). At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p<0.05). Further analysis showed all nine NMSS sub-domain changes favoring the liraglutide group, with one (attention/memory) reaching statistical significance (p<0.05). Secondary outcome analyses revealed a significant improvement of PDQ-39 (p<0.001) and Parkinson’s Anxiety Scale - Avoidance Behavior scores (p<0.05) in the treatment group. MDRS-2 sub-scores did not further differentiate study groups, while DKEFS letter fluency scores favored placebo group (p<0.05).

Treatment with liraglutide improved self-reported non-motor symptoms of PD, activities of daily living, and quality of life. These results validate similar outcomes reported with other GLP-1 agonists implicating consideration for novel treatment opportunities for individuals with PD. Notably, the absence of significant performance-based cognitive changes over the duration of the trial for the participants in this study has several plausible explanations given participant-related baseline demographic and clinical factors. Implications for neuropsychologists will be discussed.

Alzheimer’s disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity.

Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24–60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively.

There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence.

iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.