Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

Nebes, Robert D.; Pollock, Bruce G.; Halligan, Edythe M.; Houck, Patricia R.; Saxton, Judith

doi:10.1097/jgp.0b013e3181e4490d

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…From the aforementioned studies, majority examined (n = 24) an association between SAA and cognitive outcomes [ 7 , 8 , 10 – 13 , 40 – 50 , 52 – 54 , 56 , 57 , 60 , 61 ] using mostly MMSE as a standard measure of cognitive performance. Limited studies (n = 8) reported an association between SAA and both cognitive, and functional outcomes [ 14 , 16 – 18 , 55 , 57 – 59 ].…”

Section: Resultsmentioning

confidence: 99%

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

2016

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IntroductionStudies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people.Materials and MethodsA literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946–2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests.ResultsThe primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value = <0.05) however, the pooled data from 4 observational studies showed elevated SAA was associated with reduced cognitive performance (I2 = 0.00%, H2 = 3.37 and p-value = 0.34).ConclusionThis systematic review summarises the limitations of the SAA on predicting cognitive and functional outcomes in older people. SAA measured by receptor bioassay is flawed and its use in older people with multimorbidity and polypharmacy is questionable.

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Section: Resultsmentioning

confidence: 99%

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

2016

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“…This could help explain the lack of beneficial effect of estrogen therapy on cognitive performance in older women who have not used estrogen therapy for many years, such as in the very large and highly publicized Women’s Health Initiative Memory Study (Coker et al, 2010). Use of co-medications with significant anti-cholinergic activity also could significantly curtail the beneficial effects of estrogen therapy on cognitive performance and contribute to diminished effect in specific patient populations (Carriere et al, 2009; Nebes et al, 2010; Vinogradov et al, 2009). Collectively, these findings suggest that combining a cholinesterase inhibitor with E2 therapy may be most effective in recently postmenopausal women or women with early signs of mild cognitive impairment or AD, and least effective in women with advanced AD or who are on medications with significant anti-cholinergic activity.…”

Section: Discussionmentioning

confidence: 99%

Donepezil plus estradiol treatment enhances learning and delay-dependent memory performance by young ovariectomized rats with partial loss of septal cholinergic neurons

Gibbs

Chipman

Nelson

2011

Hormones and Behavior

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Effects of estrogen therapy on cognitive performance appear to diminish with age and time following the loss of ovarian function. We hypothesize that this is due to a reduction in basal forebrain cholinergic function and that treatment with a cholinergic enhancer can reverse the effect. This study tested whether combining the cholinesterase inhibitor donepezil with estradiol treatment can enhance/restore estradiol effects on cognitive performance in young ovariectomized rats with selective lesions of septal cholinergic neurons. 192IgG-saporin was injected directly into the medial septum to produce selective cholinergic lesions. Rats were then treated with donepezil (Don, daily injections of 3 mg/Kg/day, i.p.) or vehicle, and then with 17β-estradiol (E2, administered by silastic capsule implanted s.c.) or an empty capsule. Rats were trained on a delayed matching-to-position (DMP) T-maze task which previous studies have shown is sensitive to ovariectomy and estrogen replacement. Results show that neither estradiol nor donepezil alone significantly enhanced acquisition of the DMP task in rats with cholinergic lesions. Combination therapy was effective, however, depending on the severity of the lesion. Don+E2 significantly enhanced acquisition of the task in rats with partial lesions (<50% loss of cholinergic neurons), but not in rats with severe lesions. This effect was due largely to a reduction in perseverative behavior. Don+E2 also improved working memory in rats with partial lesions, as evidenced by significantly better performance than controls during increased intertrial delays. These findings suggest that even partial loss of septal cholinergic neurons can reduce effects of estrogen therapy on cognitive performance, and demonstrate that combining a cholinesterase inhibitor with estrogen therapy can help to restore beneficial effects on performance. We propose that combination therapy may have similar beneficial effects in women, particularly in older women who have not used estrogen therapy for many years and are beginning to show signs of cognitive impairment or early Alzheimer’s disease.

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“…Indeed, Karachi et al recently wrote that “cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD” [115]. Another possibility is that the cholinergic changes reflect more general cognitive deficits and are not necessarily PPN-mediated; serum levels of cholinergic activity have also been related to reaction times and cognitive slowing [114,116]. …”

Section: Neuroimaging Evidence Linking Cognitive Function and Gaitmentioning

confidence: 99%

The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?

Segev-Jacubovski

Herman

Yogev‐Seligmann

et al. 2011

Expert Review of Neurotherapeutics

253

171

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In this article, we briefly summarize the incidence and significant consequences of falls among older adults, the insufficient effectiveness of commonly used multifactorial interventions and the evidence linking falls and cognitive function. Recent pharmacologic and nonpharmacologic studies that evaluated the effects of cognitive therapy on fall risk are reviewed. The results of this article illustrate the potential utility of multiple, diverse forms of cognitive therapy for reducing fall risk. The article also indicates that large-scale, randomized controlled trials are warranted and that additional research is needed to better understand the pathophysiologic mechanisms underlying the interplay between human mobility, fall risk and cognitive function. Nonetheless, we suggest that multimodality interventions that combine motor and cognitive therapy should, eventually, be incorporated into clinical practice to enable older adults and patients to move safer and with a reduced fall risk.

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Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

Cited by 9 publications

References 33 publications

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

Donepezil plus estradiol treatment enhances learning and delay-dependent memory performance by young ovariectomized rats with partial loss of septal cholinergic neurons

The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?

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