The value of multimodal imaging with 123I-FP-CIT SPECT in differential diagnosis of dementia with Lewy bodies and Alzheimer's disease dementia.

Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-[123I]iodophenyl) nortropane (123I-FP-CIT) SPECT reflects dopamine dysfunction, while other imaging markers could be complementary when used together. We assessed how well 123I-FP-CIT SPECT differentiates dementia with Lewy bodies (DLBs) from Alzheimer's disease dementia (ADem) and whether multimodal imaging provides additional value. 123I-FP-CIT SPECT, magnetic resonance imaging, [18F]2-fluoro-deoxy-D-glucose-positron emission tomography (PET), and 11C-Pittsburgh compound B (PiB)-PET were assessed in 35 participants with DLBs and 14 participants with ADem (autopsy confirmation in 9 DLBs and 4 ADem). Nigrostriatal dopamine transporter uptake was evaluated with 123I-FP-CIT SPECT using DaTQUANT software. Hippocampal volume was calculated with magnetic resonance imaging, cingulate island sign ratio with FDG-PET, and global cortical PiB retention with PiB-PET. The DaTQUANT z-scores of the putamen showed the highest c-statistic of 0.916 in differentiating DLBs from ADem among the analyzed imaging biomarkers. Adding another imaging modality to 123I-FP-CIT SPECT had c-statistics ranging from 0.968 to 0.975, and 123I-FP-CIT SPECT in combination with 2 other imaging modalities presented c-statistics ranging from 0.987 to 0.996. These findings suggest that multimodal imaging with 123I-FP-CIT SPECT aids in differentiating DLBs and ADem and in detecting comorbid Lewy-related and Alzheimer's disease pathology in patients with DLBs and ADem.

Comparative Effectiveness of Behavioral Interventions on Quality of Life for Older Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Recommendations to engage in behavioral strategies to combat clinically significant cognitive and behavioral symptoms are routinely given to persons with mild cognitive impairment (MCI). The comparative effectiveness of these behavioral interventions is not well understood. Objective: To compare the incremental effects of combinations of 5 behavioral interventions on outcomes of highest importance to patients with MCI. Design, Setting, and Participants: In this multisite, cluster randomized, multicomponent comparative effectiveness trial, 272 patients from 4 academic medical outpatient centers (Mayo Clinic, Rochester, Minnesota; Mayo Clinic, Scottsdale, Arizona; Mayo Clinic, Jacksonville, Florida; and University of Washington, Seattle) were recruited from September 1, 2014, to August 31, 2016, with last follow-up March 31, 2019. All participants met the National Institute on Aging-Alzheimer's Association criteria for MCI. Interventions: The intervention program was modeled on the Mayo Clinic Healthy Action to Benefit Independence and Thinking (HABIT) program, a 50-hour group intervention conducted during 2 weeks, including memory compensation training, computerized cognitive training, yoga, patient and partner support groups, and wellness education. In our study, 1 of 5 interventions was randomly selected to be withheld for each intervention group. Participants and their partners had 1-day booster sessions at 6 and 12 months after intervention. Main Outcomes and Measures: Quality-of-life measurement of participants with MCI at 12 months was the primary outcome, selected based on the preference rankings of previous program participants. Mood, self-efficacy, and memory-based activities of daily living were also highly ranked. Results: A total of 272 participants (mean [SD] age, 75 [8] years; 160 [58.8%] male and 112 [41.2%] female) were enrolled in this study, with 56 randomized to the no yoga group, 54 to no computerized cognitive training, 52 to no wellness, 53 to no support, and 57 to no memory support system. The greatest effect size for quality of life was between the no computerized cognitive training and no wellness education groups at 0.34 (95% CI, 0.05-0.64). In secondary analyses, wellness education had a greater effect on mood than computerized cognitive training (effect size, 0.53; 95% CI, 0.21-0.86), and yoga had a greater effect on memory-related activities of daily living than support groups (effect size, 0.43; 95% CI, 0.13-0.72). Conclusions and Relevance: These results provide further support for behavioral interventions for persons with MCI. Different outcomes were optimized by different combinations of interventions. These findings provide an initial exploration of the effect of behavioral interventions on patient-advocated outcomes in persons with MCI. Trial Registration: ClinicalTrials.gov identifier: NCT02265757.

Pulse width is associated with cognitive decline after thalamic stimulation for essential tremor.

The present study sought to identify predictors of cognitive decline after thalamic deep brain stimulation (DBS) for essential tremor (ET). Twenty-seven patients (55%) with ET demonstrated mild cognitive decrements relative to pre-surgical baseline (ET-D), whereas 22 patients (45%) were classified as neuropsychologically stable (ET-S). The ET-D and ET-S groups were comparable in terms of baseline demographic, disease, and neuropsychological characteristics, as well as post-surgical motor outcomes. However, the ET-D group had significantly higher pulse width (PW) stimulator settings, and a greater proportion of ET-D than ET-S patients underwent left in comparison to right thalamic stimulation. A subsequent step-wise discriminant function analysis revealed that disease onset after age 37 years and higher PW settings (>or=120 micros) were the strongest predictors of post-surgical cognitive decline in this sample. Findings indicate that although relatively higher PW settings might afford optimal tremor control in some patients, the corresponding risk of mild, probably often subclinical, cognitive morbidity must be weighed accordingly.

Effect of motor improvement on quality of life following subthalamic stimulation is mediated by changes in depressive symptomatology.

BACKGROUND/AIMS: Subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves motor symptoms and quality of life (QOL). Because depression is a potent correlate of QOL, and STN-DBS may be associated with changes in mood, this study sought to determine whether QOL improvement is a direct or indirect consequence of motor improvement. METHODS: 26 patients with PD, free of dementia and major depression, who consecutively underwent bilateral, microelectrode-guided STN-DBS, underwent preoperative and 3-month postoperative neuropsychological evaluation, including measures of QOL (PD Questionnaire -39) and depressive symptoms (Beck Depression Inventory). RESULTS: Motor score in the Unified Parkinson's Disease Rating Scale (UPDRS Part III) improved significantly with STN-DBS relative to preoperative 'on' and 'off' scores, as did QOL and depressive symptoms. Extent of QOL improvement tended to be associated with improvement in motor score from presurgical on to postsurgical on stimulation and on medication state. QOL improvement was significantly related to amelioration of depressive symptoms. Partial correlations revealed that the association between QOL improvement and depression remained significant when influence of motor improvement on QOL and depression was controlled for. The motor-QOL association was no longer significant when effects of depression were controlled for. CONCLUSIONS: Significant QOL improvements after STN-DBS are associated with improved motor 'on' state and depressive symptoms. The influence of motor improvement on QOL may be largely indirect by reducing depression.

Declines in switching underlie verbal fluency changes after unilateral pallidal surgery in Parkinson's disease.

Declines in verbal fluency are consistently reported in patients with Parkinson's disease (PD) after pallidal surgery. In the present study, the clustering and switching components of semantic or category fluency (oral naming of items obtainable in supermarkets) were examined at baseline and four months after unilateral deep brain stimulation or pallidotomy in 45 patients with PD (30 left, 15 right pallidal surgery). Post-operative declines were observed for supermarket fluency total score and switching, but not for average cluster size. These findings support the proposal that semantic fluency decrements after pallidal surgery reflect a disruption of frontal-basal ganglia circuits mediating efficient shifting between semantic categories, or perhaps efficient access to categories, rather than a degradation of semantic stores.

Neuropsychological sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a critical review.

Neuropsychologists are increasingly involved in surgical candidacy evaluations and postoperative neurobehavioral assessments of patients with movement disorders, most notably those with Parkinson's disease (PD). We review here the initial studies regarding neuropsychological outcomes of deep brain stimulation (DBS) within the subthalamic nucleus (STN) for treatment of PD. Overall, these initial investigations provide preliminary support for the cognitive and neurobehavioral safety of STN DBS. Improvements in self-reported symptoms of depression and diminished verbal fluency were the most common findings, whereas changes in global cognitive abilities, memory, attention, and frontal/executive functions were inconsistent and most often described as nominal and/or transient. The generalizability of this literature is hindered by several methodological limitations, including small samples and the absence of appropriate control participants. The clinical and theoretical implications of these initial studies are highlighted and recommendations are offered to guide future research.