Defining “Prodromal” Alzheimer’s Disease, Frontotemporal Dementia, and Lewy Body Dementia: Are we There Yet?

Welsh-Bohmer, Kathleen A.

doi:10.1007/s11065-008-9057-y

Cited by 18 publications

(7 citation statements)

References 11 publications

(8 reference statements)

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“…Dementia is a progressive disease with an asymptomatic latent phase of several decades, followed by a prodromal phase of several years where symptoms cannot be differentiated from normal cognitive changes associated with aging. 30,31 Assessing the effects of PPIs requires looking at the biologically relevant period. If PPIs trigger dementia, we need to examine use prior to latent phase onset, if they accelerate its development, we should examine the latent phase.…”

Section: Study Highlightsmentioning

confidence: 99%

Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?

Friesen

Falk

Château

et al. 2022

Clin Pharma and Therapeutics

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The association between proton pump inhibitor (PPI) use and dementia remains controversial. This cohort study re-examines this issue, addressing shortcomings identified in previous publications using a population-based and a high-dimension propensity-score matched cohort to follow patients for up to 22 years. Cox regression models using baseline characteristics, a lag period, and time-varying variables were used to examine the risk of dementia by cumulative PPI exposure. High-dose PPI users (> 180 days of use) had significantly higher risk of dementia in crude Cox models. After adjustment for medical diagnoses and prescription drug use, these associations disappeared. Among high-dose users starting PPI therapy between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 (95% CI 0.80, 1.51). For high-dose users starting therapy between 56 and 65 years, HR = 1.22 (95% CI1.03, 1.44); aHR = 0.99 (95% CI 0.83, 1.17). High-dose users between the ages of 66 and 75 years had no association with the risk of dementia. The use of lag models or time-varying parameters similarly found some association with dementia in crude, but not multivariable Cox models. Although high-dose PPI users were more likely to develop dementia, they were more likely to be diagnosed with dementia risk factors, such as diabetes and cardiovascular disease, which are risk factors for dementia. Controlling for these conditions using multivariable models or a propensity-score matched cohort eliminated this association.

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Section: Study Highlightsmentioning

confidence: 99%

Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?

Friesen

Falk

Château

et al. 2022

Clin Pharma and Therapeutics

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“…For simplicity in the present review, we refer to the prodromal stage of all these dementias as mild cognitive impairment (MCI). MCI is conceptualized as an early expression of a neurodegenerative disorder, affecting cognition but not functional independence (Welsh-Bohmer, 2008 ; Benke, 2011 ), for which the pathological processes (e.g., proteopathy, tauopathy, synucleinopathy, etc.) are not yet known.…”

Section: Introductionmentioning

confidence: 99%

Adult ADHD: Risk Factor for Dementia or Phenotypic Mimic?

Callahan

Bierstone

Stuss

et al. 2017

Front. Aging Neurosci.

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Attention-deficit hyperactivity disorder (ADHD) has historically been considered a disorder of childhood and adolescence. However, it is now recognized that ADHD symptoms persist into adulthood in up to 60% of individuals. Some of the cognitive symptoms that characterize ADHD (inability to provide sustained attention or mental effort, difficulty organizing or multi-tasking, forgetfulness) may closely resemble symptoms of prodromal dementia, also often referred to as mild cognitive impairment (MCI), particularly in patients over age 50. In addition to the overlap in cognitive symptoms, adults with ADHD and those with MCI may also share a number of behavioral and psychiatric symptoms, including sleep disturbances, depression, and anxiety. As a result, both syndromes may be difficult to distinguish clinically in older patients, particularly those who present to memory clinics with subjective cognitive complaints and fear the onset of a neurodegenerative process: is it ADHD, MCI, or both? Currently, it is unclear whether ADHD is associated with incipient dementia or is being misdiagnosed as MCI due to symptom overlap, as there exist data supporting either possibility. Here, we aim to elucidate this issue by outlining three hypothetical ways in which ADHD and MCI might relate to each other, providing an overview of the evidence relevant to each hypothesis, and delineating areas for future research. This is a question of considerable importance, with implications for improved diagnostic specificity of early dementia, improved accuracy of disease prevalence estimates, and better identification of individuals for targeted treatment.

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“…, Mesulam et al . , Welsh‐Bohmer ). Findings of this study further highlight the importance of obtaining qualitative information to identify emerging symptoms of PPA.…”

Section: Discussionmentioning

confidence: 99%

“…It may be particularly difficult to determine with limited contextual information if the observed behaviour is due to mild depression/anxiety as a consequence of the language impairment, or indeed a manifestation of the NCD (Modirrousta et al 2013, Singh et al 2015. It is also acknowledged that behaviouralneuropsychiatric symptoms in FTD disorders are not as readily and reliably identified and captured by available neuropsychological measures and generally available neuroimaging techniques, such as CT and standard magnetic resonance imaging (MRI) (Hallam et al 2008, Mesulam et al 2012, Welsh-Bohmer 2008. Findings of this study further highlight the importance of obtaining qualitative information to identify emerging symptoms of PPA.…”

Section: Discussionmentioning

confidence: 99%