Cholinergic Functions and Modulation of the Cingulo-opercular Alertness Network in LBD
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Dementia Cognitive Fluctuations Scale
研究概览
简要总结
Fluctuations in alertness are very common in persons with Lewy body dementias and are a major source of disability. Changes in a chemical messenger molecule called acetylcholine within certain brain regions may play a role in these fluctuations. We propose to test this hypothesis and also determine whether a non-invasive way of stimulating affected brain regions may be of relevance for future management of these fluctuations.
详细描述
The central premise of the research study was that cholinergic system changes in specific neural network regions underlie cognitive fluctuations in patients with LBD. The cingulo-opercular task control (COTC) neural network is believed to play a role in maintenance of alertness but this remains uncertain in LDB. This critical knowledge gap formed the basis of the study's first aim. The study proposed to use transcranial direct current stimulation (tDCS) to "excite" critical cholinergic denervation components of the COTC as an adjunct to cholinergic pharmacotherapy in a target engagement study. tDCS is an emerging non-invasive neurostimulation technology that may improve a range of neurological symptoms, including cognition. The study evaluated whether target engagement by tDCS excitation of cholinergic denervated COTC hubs may affect cognitive fluctuations in LBD subjects.
While the cingulo-opercular network was expected to be the primary site of cholinergic denervation based on preliminary evidence, and thus the focus of the stimulation intervention, the typical pattern of cholinergic denervation in our sample occurred at a temporal lobe region that is classified as a node of the ventral attention network in the Gordon atlas. Additional results from examining different networks have been added to reflect the unanticipated relocation of stimulation location.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Investigator, Outcomes Assessor, and Participant/Care Provider will all know the participant is receiving intervention/stimulation. There is no placebo condition.
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •LBD patients (DLB or PDD) who have cognitive fluctuations and who are on stable doses of cholinesterase inhibitors (i.e., at least 4 weeks) will be recruited to participate in this study.
- •DLB patients will meet the Fourth consensus report of the DLB Consortium inclusion criteria for probable DLB.
- •Subjects will be identified according to the following recognized DLB features: spontaneous parkinsonian motor signs, fluctuating attention and concentration, recurrent well-formed visual hallucinations, presence of REM behavioral sleep disturbance, anosmia/hyposmia,or autonomic dysfunction.
- •PDD patients will meet the criteria by Emre et al. (Cognitive deficits in at least two of four of the following cognitive domains: Impaired attention, impaired executive functions, impairment in visuo-spatial functions, impaired free recall memory typically improved with cuing. Must also meet criteria for at least one behavioral symptom: apathy, depressed or anxious mood, hallucinations, delusions, excessive daytime sleepiness). Lack of behavioral symptoms does not exclude the diagnosis. Must also have none of Group III features present: (1) Co-existence of any other abnormality which might cause impairment, but judged not to be the cause of dementia. (2) Time interval between development of motor and cognitive symptoms not known. Must also have none of Group IV symptoms present: (1) Cognitive and behavioral symptoms appear solely in the context of other conditions such as acute confusion caused by systemic diseases or abnormalities, drug intoxication, or major depression according to DSM IV. (2) Features compatible with Probable Vascular Dementia criteria accordingly to NINDS-AIREN.
排除标准
- •Subjects with contra-indications to MR imaging and/or tDCS, including pacemakers or claustrophobia
- •Evidence of large vessel stroke or mass lesion on MRI
- •Use of anti-cholinergic or neuroleptic drugs
- •Evidence of atypical parkinsonism on neurological exam
- •Major psychiatric illness, such as bipolar disorder
- •Neurological conditions such as epilepsy, stroke, multiple sclerosis, or moderate to severe brain injury
- •Sensory impairments that significantly limit one's ability to see or hear
- •A significant history of recent alcohol or drug dependence
- •Previous major radiation exposure
- •Pregnancy
研究组 & 干预措施
Experimental: HD-tDCS
Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models.
干预措施: HD-tDCS (Device)
结局指标
主要结局
Dementia Cognitive Fluctuations Scale
时间窗: Baseline and Post-Testing (3-4 weeks)
Score on a 4-item subscale of the 17-item Dementia Cognitive Fluctuation Scale (DCFS), developed to address limitations in prior scales and has good test-retest and inter-rater reliability; this subscale highly discriminates between dementia with Lewy bodies (DLB) and other dementia groups. The DCFS is a subjective report of cognitive fluctuation, the spontaneous change in cognitive ability which is a core diagnostic feature of DLB. Total subscale scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations. A decrease in score between Baseline and Post-Testing indicates an improvement in cognitive fluctuation.
次要结局
- Resting State fMRI(Baseline and Post-Testing (3-4 weeks))
- Stroop Color Word Interference Test - Cognitive Control Performance(Baseline, 3-4 weeks)
- Objective Measures of Working Memory (N-back Test)(Baseline, 3-4 weeks)
研究者
Benjamin Hampstead, PhD
Professor
University of Michigan