Evidence for Different Trajectories of Delay Discounting in Older Adults With Mild Cognitive Impairment and Mild Alzheimer’s Disease

Thoma, Myriam V.; Maercker, Andreas; Forstmeier, Simon

doi:10.1093/geronb/gbw010

Cited by 11 publications

(11 citation statements)

References 45 publications

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“…Our data have revealed that synapses of Aldh1a1 neurons are degenerated and associated with the impairments of the behavioral options for a large delayed reward. This finding supports the previous reports that impulsive behaviors occur in the early stage of human patients with AD [ 39 , 40 ]. Notably, an early study indicates that AD patients displayed significantly difference from control group in the degree of impulsive behaviors at one-month or one-year delay assay, but they had no difference from control group in the degree of impulsive behaviors at ten-years delay measurements [ 57 ].…”

Section: Discussionsupporting

confidence: 93%

“…Impulsive behavior occurs at the early stage of AD [ 39 , 40 ]. Subsequently, we examined Aldh1a1 → EGNIS synaptic transmission in heterozygous APPswe/PSEN1dE9 mutant mice (AD mice) carrying a transgene encoding the 695-amino-acid isoform of the human Aβ precursor protein with the Swedish mutation and a mutant human presenilin1 (PS1-dE9), which displayed impulsive behaviors when they were 5 months old, as compared with non-transgenic control C57BL/6 mice (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors

Chen

Huang

et al. 2021

Mol Neurodegeneration

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Background Aldh1a1 neurons are a subtype of gamma-aminobutyric acid (GABA) inhibitory neurons that use Aldh1a1 rather than glutamate decarboxylase (GAD) as an enzyme for synthesizing GABA transmitters. However, the behaviors and circuits of this newly identified subtype of inhibitory interneurons remain unknown. Methods We generated a mutant mouse line in which cyclization recombination enzyme (CRE) was expressed under the control of the Aldh1a1 promotor (Aldh1a1-CRE mice). Using this mutant strain of mice together with the heterozygous male Alzheimer’s disease (AD) related model mice (APPswe/PSEN1dE9, or AD mice) and a genetically modified retrograde and anterograde synaptic tracing strategy, we have studied a specific synaptic circuit of Aldh1a1 neurons with system-level function and disease progression in AD mice. Results We demonstrate that Aldh1a1 neurons encode delay of gratification that measures self-control skills in decision making by projecting inhibitory synapses directly onto excitatory glutamate neurons in the intermediate lateral septum (EGNIS) and receiving synaptic inputs from layer 5b pyramidal neurons in the medial prefrontal cortex (L5PN). L5PN → Aldh1a1 synaptic transmission undergoes long-term potentiation (LTP). Pathway specific inhibition by either genetic silencing presynaptic terminals or antagonizing postsynaptic receptors impairs delay of gratification, resulting in the impulsive behaviors. Further studies show that reconstitution of Aldh1a1-deficient neurons with the expression of exogenous Aldh1a1 (eAldh1a1) restores Aldh1a1 → EGNIS synaptic transmission and rescues the impulsive behaviors in AD mice. Conclusions These results not only identify a specific function and circuit of Aldh1a1 neurons but also provide a cellular point of entry to an important but understudied synaptic mechanism for the induction of impulsive behaviors at an early stage of AD.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors

Chen

Huang

et al. 2021

Mol Neurodegeneration

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“…We set the upper age limit at 63 years to limit the potential confounding effect of older age. Older adults may show a greater preference for immediate over delayed rewards [35], and this preference may be stronger among older adults with mild cognitive impairment [36-38] and Alzheimer disease [37,38]. On the other hand, other studies indicate that older adults may show a greater preference for delayed rewards compared with middle-aged adults [36].…”

Section: Methodsmentioning

confidence: 99%

The Effects of Positive Affect and Episodic Future Thinking on Temporal Discounting and Healthy Food Demand and Choice Among Overweight and Obese Individuals: Protocol for a Pilot 2×2 Factorial Randomized Controlled Study

Levens¹,

Sagui-Henson²,

Padro³

et al. 2019

JMIR Res Protoc

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Background Unhealthy behaviors (eg, poor food choices) contribute to obesity and numerous negative health outcomes, including multiple types of cancer and cardiovascular and metabolic diseases. To promote healthy food choice, diet interventions should build on the dual-system model to target the regulation and reward mechanisms that guide eating behavior. Episodic future thinking (EFT) has been shown to strengthen regulation mechanisms by reducing unhealthy food choice and temporal discounting (TD), a process of placing greater value on smaller immediate rewards over larger future rewards. However, these interventions do not target the reward mechanisms that could support healthy eating and strengthen the impact of EFT-anchored programs. Increasing positive affect (PosA) related to healthy food choices may target reward mechanisms by enhancing the rewarding effects of healthy eating. An intervention that increases self-regulation regarding unhealthy foods and the reward value of healthy foods will likely have a greater impact on eating behavior compared with interventions focused on either process alone. Objective This study aimed to introduce a protocol that tests the independent and interactive effects of EFT and PosA on TD, food choice, and food demand in overweight and obese adults. Methods This protocol describes a factorial, randomized, controlled pilot study that employs a 2 (affective imagery: positive, neutral) by 2 (EFT: yes, no) design in which participants are randomized to 1 of 4 guided imagery intervention arms. In total, 156 eligible participants will complete 2 lab visits separated by 5 days. At visit 1, participants complete surveys; listen to the audio guided imagery intervention; and complete TD, food demand, and food choice tasks. At visit 2, participants complete TD, food demand, and food choice tasks and surveys. Participants complete a daily food frequency questionnaire between visits 1 and 2. Analyses will compare primary outcome measures at baseline, postintervention, and at follow-up across treatment arms. Results Funding notification was received on April 27, 2017, and the protocol was approved by the institutional review board on October 6, 2017. Feasibility testing of the protocol was conducted from February 21, 2018, to April 18, 2018, among the first 32 participants. As no major protocol changes were required at the end of the feasibility phase, these 32 participants were included in the target sample of 156 participants. Recruitment, therefore, continued immediately after the feasibility phase. When this manuscript was submitted, 84 participants had completed the protocol. Conclusions Our research goal is to develop novel, theory-based interventions to promote and improve healthy decision-making and behaviors. The findings will advance decision-making research and have the potential to generate new neuroscience and psychological research to further un...

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“…People with MCI may display significantly higher levels of DD, which indicates that they tend to respond to smaller rewards impulsively (Lindbergh et al, 2014). Compared to MCI patients and older adults, AD patients display even higher DD (Lebreton et al, 2013;Thoma et al, 2017;El Haj et al, 2020;Geng et al, 2020). These findings are probably related to impaired autobiographical memory in patients with AD (El Haj et al, 2020) and executive function deficits in patients with MCI (Geng et al, 2020).…”

Section: Cognitive Impairmentmentioning

confidence: 99%

Decision-Making Support for People With Alzheimer’s Disease: A Narrative Review

2021

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The proportion of people with dementia has been increasing yearly, and the decision-making capacity of these people has become a major concern in fields such as the financial industry and in medical settings. In this narrative review, we discuss decision-making in people with Alzheimer’s disease (AD), and we propose the support for decision-making in people with AD, especially financial and medical decision-making. We summarize several hypotheses and theories on the decision-making capacity of people with AD. These include the frontal lobe hypothesis, physiological theory, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and the Person-Task-Fit (PTF) framework. Both internal and external factors can affect decision-making by people with AD. Internal factors are affected by changes in the brain and neurotransmitters, as well as alterations in cognitive ability and emotion. External factors include task characters, task contents, and situation influence. Since feedback has a significant effect on decision-making capacity, a series of suggestions may be helpful to improve this capacity, such as explicit advice, simple options, pleasant rewards, the Talking Mats approach, memory and organizational aid, support by caregivers, cognitive training and feedback. Thus, in providing decision-making support for people with AD, it is important to identify the internal and external factors that impair this process and to deal with these factors.

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Evidence for Different Trajectories of Delay Discounting in Older Adults With Mild Cognitive Impairment and Mild Alzheimer’s Disease

Abstract: Our results point toward an increase in DD as a function of advanced cognitive decline.

Cited by 11 publications

References 45 publications

Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors

Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors

The Effects of Positive Affect and Episodic Future Thinking on Temporal Discounting and Healthy Food Demand and Choice Among Overweight and Obese Individuals: Protocol for a Pilot 2×2 Factorial Randomized Controlled Study

Decision-Making Support for People With Alzheimer’s Disease: A Narrative Review

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