Relationship between executive dysfunction and neuropsychiatric symptoms and impaired instrumental activities of daily living among patients with very mild Alzheimer's disease

Ikezaki, Hiroto; Hashimoto, Mamoru; Ishikawa, Tomohisa; Fukuhara, Ryuji; Tanaka, Hibiki; Yuki, Seiji; Kuribayashi, Koichiro; Hotta, Maki; Koyama, Asuka; Ikeda, Manabu; Takebayashi, Minoru

doi:10.1002/gps.5308

Cited by 13 publications

(9 citation statements)

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“…In eight studies (13%), clinicians established NPS based on a DSM diagnosis, an ICD-9 diagnosis, or criteria for depression in AD [ 24 ], psychosis in AD [ 27 ], or apathy in AD [ 35 ]. Information on the characteristics of the informant who rated NPS was reported in four studies [ 36 – 39 ], of which two reported these characteristics for male and female patients separately [ 37 , 38 ]. The majority of the informants were the spouse [ 36 – 39 ], which was primarily the case for male patients (66–86% for male patients and 21–38% in female patients) [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…Information on the characteristics of the informant who rated NPS was reported in four studies [ 36 – 39 ], of which two reported these characteristics for male and female patients separately [ 37 , 38 ]. The majority of the informants were the spouse [ 36 – 39 ], which was primarily the case for male patients (66–86% for male patients and 21–38% in female patients) [ 37 , 38 ]. The majority of caregivers were female [ 36 – 39 ], although to a lesser extent for female patients (90% for male patients and 61% for female patients) [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis

et al. 2022

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Background Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer’s disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. Methods Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges’ g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses. Results Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS (k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity (k = 13, g = 0.04 [− 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms (k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior (k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms (k = 16, g = 0.24 [0.14, 0.34]), delusions (k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior (k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females (k = 11, g = − 0.10 [− 0.18, − 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics. Discussion Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis

et al. 2022

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“…Among them have been described the presence of neuropsychiatric symptoms which may appear before clinical manifestations of dementia and are linked to the loss of capacity of patients to perform instrumental activities of daily living. 1 , 2 The possibility of dopaminergic dysfunction has been suggested as an actor in these behavioural disorders. 1 In this sense, post-mortem studies have shown a reduction in dopamine (DA) synthesis, 3 an alteration of the neurons producing DA and DA release in the striatum and hippocampus, 4 but the impact on DA D 2 -receptor (D 2 R) density is not clear.…”

Section: Introductionmentioning

confidence: 99%

Alterations in dopamine system and in its connectivity with serotonin in a rat model of Alzheimer’s disease

Ceyzériat

Gloria

Tsartsalis

et al. 2021

Brain Communications

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Dopamine (DA) pathways alterations are reported in Alzheimer’s disease (AD). However, it is difficult in humans to establish when these deficits appear and their impact in the course of Alzheimer’s disease. In the TgF344-AD rat model at the age of 6 months, we showed a reduction in in vivo release of striatal DA due to serotonin 5HT2A-receptor (5HT2AR) blockade, in the absence of alterations in 5HT2AR binding, suggesting a reduction in 5HT2AR-DA system connectivity. In addition, a functional hypersensitivity of postsynaptic DA D2-receptors (D2R) and D2-autoreceptors was also reported without any change in D2R density and in the absence of amyloid plaques or overexpression of the 18 kDa translocator protein (TSPO, an inflammatory marker) in areas of the DA system. Citalopram, a selective serotonin reuptake inhibitor, induced functional 5HT2AR-D2R connectivity changes but had no effect on D2-autoreceptor hypersensitivity. In older rats, DA cell bodies overexpressed TSPO and DA projection sites accumulated amyloid. Interestingly, the 5HT2AR density is decreased in the accumbens subdivisions and the substantia nigra pars compacta. This reduction in the striatum is related to the astrocytic expression of 5HT2AR. Our results indicate that both serotonin/dopamine connectivity and DA signaling pathways are dysregulated and potentially represent novel early diagnostic and therapeutic avenues.

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“…The ABC symptoms are closely associated and interact with each other; [31][32][33] even in very mild AD, executive function, depression, and apathy are associated with IADL decline among female patients [35]. It is rational for clinicians to identify and assess ABC symptoms comprehensively.…”

Section: Associations Among the Abc Symptomsmentioning

confidence: 99%

Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

Jia

Liu

et al. 2021

Neurosci. Bull.

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Alzheimer's disease (AD) is the most common cognitive disorder in the elderly. Its main clinical manifestations are cognitive decline (C), behavioral and psychological symptoms (B), and a decline in the activities of daily living (A), also known as ABC symptoms. Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis, comprehensive treatment, and prognosis of AD. To guide Chinese clinical practice for optimization of the comprehensive management of AD, in 2018, The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD. Based on a review of the evidence, the consensus summarizes the pathogenesis, pathological changes, clinical manifestations, evaluation, diagnosis, drug and non-drug treatment, and patient care for AD. Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients. The new consensus provides a feasible AD management process for clinicians.

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Relationship between executive dysfunction and neuropsychiatric symptoms and impaired instrumental activities of daily living among patients with very mild Alzheimer's disease

Cited by 13 publications

References 38 publications

Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis

Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis

Alterations in dopamine system and in its connectivity with serotonin in a rat model of Alzheimer’s disease

Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

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