Linda Mah

Linda Mah
Baycrest · Rotman Research Institute, Department of Psychiatry

MD, MHS

About

92
Publications
18,830
Reads
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1,142
Citations
Additional affiliations
July 2006 - present
University of Toronto
Position
  • Professor (Assistant)
July 2006 - present
Rotman Research Institute, Baycrest, University of Toronto
Position
  • Clinician Scientist
September 2002 - June 2006
National Institute of Mental Health (NIMH)
Position
  • Research Associate

Publications

Publications (92)
Article
Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ER...
Article
Introduction Older adults are at greater risk for developing severe illness from SARS-COV2 infection and may be more vulnerable to negative mental health outcomes as a result of public health guidelines that increase social isolation. In the current study, we assessed mental health outcomes in a cohort of older adults with normal cognition (NC), pa...
Article
Introduction Older adults are at an increased risk of contracting illnesses during outbreaks such as the COVID-19 pandemic. Additionally, they have greater vulnerability to negative mental health outcomes as a consequence of public health restrictions that contribute to social isolation. Recent reviews have focused on the mental health effects of t...
Article
Major depressive disorder (MDD) is associated with an increased risk of developing dementia. The present study aimed to better understand this risk by comparing resting state functional connectivity (rsFC) in the executive control network (ECN) and the default mode network (DMN) in older adults with MDD or mild cognitive impairment (MCI). Additiona...
Article
The common requirement to set the time to “10 past 11” on the Clock Drawing Test is intended to elicit a stimulus bound response (SBR), in which the responder is “pulled” to the salient stimulus “10,” resulting in hands set at “10 before 11.” SBRs are considered markers of executive dysfunction, although this assumption has not yet been validated....
Article
Subjective cognitive decline (SCD), defined as perception of memory or other cognitive decline with normal test performance, is conceptualized as a preclinical stage of Alzheimer’s disease. Formulations of SCD typically include presence of worry or concern regarding the perceived cognitive decline. Accordingly, SCD is associated with anxiety, but i...
Article
Previous work in subjective cognitive decline (SCD) suggests that subjective memory and other cognitive concerns are more likely to be associated with mood or anxiety, rather than objective memory performance, but the overall literature is inconsistent. In the current study, subjective memory profiles were characterized to examine differences among...
Article
Theta phase‐gamma amplitude coupling (TGC) is a neurophysiological mechanism that underlies working memory (WM)1. WM is also associated with demographic, clinical, genetic and neuroimaging measures. However, the relative contributions of TGC and these measures to WM, and the relationship between TGC and these measures, remains unclear. We examined...
Article
Subjective cognitive decline (SCD) is defined as self‐report of memory or other cognitive decline with normal test performance, but there is lack of consensus regarding operational criteria for SCD. One fundamental question is whether perception of cognitive decline is sufficient to establish SCD, or whether accompanying concern or worry about the...
Article
Our previous research in emotional verbal memory in mild cognitive impairment (MCI) and work from others suggest the hypothesis that emotion dysregulation is a signature of Alzheimer’s disease (AD) risk. Whether subjective cognitive decline (SCD), conceptualized as a possible preclinical stage of AD, is associated with emotion dysregulation is unkn...
Article
Subjective cognitive decline (SCD), hypothesized as a preclinical stage of Alzheimer’s disease (AD), describes individuals with subjective cognitive concerns despite normal performance on cognitive tests (Jessen et al., 2014). The reduced ability of the salience network (SN) to control switching between the central executive network (CEN) and the d...
Article
Older adults with subjective cognitive decline (SCD) show alterations in functional connectivity of the posterior default mode network (DMN), but both increases and decreases have been reported, suggesting that changes in connectivity may be nonlinear across the AD spectrum. Alternatively, the variable findings may be attributable to heterogeneity...
Article
Mild Cognitive Impairment (MCI) and Major Depressive Disorder (MDD) are independently associated with increased risk of dementia. Cerebrospinal fluid (CSF) and neuroimaging biomarkers can help to elucidate the etiology of cognitive impairment. We compared CSF biomarker profiles of Alzheimer’s disease (AD) and white matter hyperintensities (WMH) acr...
Article
Theta-gamma coupling (TGC) is a neurophysiologic mechanism that supports working memory (WM). TGC is associated with N-back performance, a WM task. Similar to TGC, theta and alpha event-related synchronization (ERS) and desynchronization (ERD) are also associated with WM. Few studies have examined the longitudinal relationship between WM performanc...
Article
Heart rate variability (HRV) is a well-established surrogate of cardiac and emotional health that reflects the balance between sympathetic and parasympathetic activity of the autonomic nervous system. We examined the impact of manipulating exhalation to inhalation ratio (E:I) on HRV, without altering the intrinsic breathing rate of healthy individu...
Article
Background: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. O...
Article
Introduction Apolipoprotein (APOE) ε4 is one of the strongest genetic biomarkers for Alzheimer's disease (AD) however, the relationship between APOE and Neuropsychiatric Symptoms (NPS) remains unclear. Our recent analyses suggested that female sex modulated the association of APOE ε4 on specific NPS domains such as psychosis¹ and nighttime behaviou...
Article
Introduction In addition to being at greater risk for severe illness and fatality during infectious outbreaks, older adults are also vulnerable to mental and physical health risks due to increased social isolation. Studies on the mental health effects of the COVID-19 pandemic are rapidly emerging, with reviews focused on the prevalence of psychiatr...
Article
Neuropsychiatric symptoms (NPS) such as depression, apathy and agitation are common in neurocognitive disorders such as Alzheimer's disease (AD) and its prodrome, Mild Cognitive Impairment (MCI). Importantly, the presence of NPS is a prognostic indicator of future decline in MCI and AD and reduces quality of life in both patients and caregivers. Ph...
Article
OBJECTIVE This study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging–Alzheimer's Association (NIA-AA) criteria vs. 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIG...
Article
Full-text available
Introduction: The biological mechanisms linking mild cognitive impairment (MCI) and major depressive disorder are not well understood. We investigated whether molecular senescence changes in older adults are associated with a history of major depressive disorder (MDD) or MCI. Methods: We included 371 participants: 167 with MCI; 62 cognitively no...
Article
Objectives To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimu...
Article
Objectives Anticholinergic burden has been associated with deleterious effects on cognition particularly in those with an underlying brain disorder. We developed a new assay based on cultured cells to measure serum anticholinergic activity (cSAA). We report on its relationships with established anticholinergic burden rating scales and cognitive ass...
Article
The Apolipoprotein E (APOE) ε4 allele is a well‐established genetic risk factor of Alzheimer's disease (AD). While sex may play an important modulatory role in the association between APOε4 and certain neuropsychiatric symptoms (NPS) in AD1, it is unclear whether or not this risk extends to cognitively at‐risk populations with Mild Cognitive Impair...
Article
Subjective cognitive decline (SCD) increases the risk of developing Alzheimer's disease (AD) but the neural mechanisms underlying this association remain unclear. Multimodal neuroimaging studies suggest that large‐scale network disruptions occur before amyloid plaques appear in the brain, beginning with alterations in the posterior default mode net...
Article
Theta‐gamma coupling (TGC) is an electroencephalography (EEG) marker of working memory and depends on robust synaptic plasticity within the recurrent prefrontal cortical networks (Rajji et al. 2017, Buszaski et al. 2012). ApoE4 allele has deleterious effects on synaptic plasticity (Teter et al. 2004). Thus, the primary objective of this analysis is...
Article
Mild Cognitive Impairment (MCI) and Major Depressive Disorder (MDD) have been independently associated with increased risk of dementia. Cerebrospinal fluid (CSF) biomarkers associated with Alzheimer’s disease (AD) show changes prior to the onset of symptoms of dementia or neuroimaging biomarkers of AD. We examined the association between a CSF biom...
Article
A high anticholinergic burden has been associated with deleterious effects on cognition, especially in the elderly. We developed a new serum anticholinergic assay (SAA) to measure the anticholinergic burden, and report on validating this new SAA using established anticholinergic burden scales and cognitive assessments in older patients with mild co...
Article
Ordering of information is a critical component that underlies several cognitive functions. Prefrontal theta–gamma coupling (TGC) is a neurophysiologic measure associated with ordering of information during the performance of a working memory task (N-back). Little is known about the relationship between TGC and ordering during other cognitive tasks...
Article
Background: By the time Alzheimer's disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed. Objective: To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups. Methods: We report on the rationale and describ...
Article
Full-text available
γ-aminobutyric acid (GABA), primary inhibitory neurotransmitter in the brain, plays a significant role in aging and in neurodegenerative disorders, including Alzheimer’s disease (AD). We investigated the relationship between GABA levels in the dorsomedial/dorsoanterolateral prefrontal cortex (DM/DA-PFC) and memory in high-AD risk participants. Thir...
Article
A history of depression is a risk factor for dementia. Despite strong epidemiologic evidence, the pathways linking depression and dementia remain unclear. We assessed structural brain alterations in white and gray matter of frontal-executive and corticolimbic circuitries in five groups of older adults putatively at-risk for developing dementia—remi...
Article
OBJECTIVE The objective of this study is to characterize functional competence (measure of assistance needed for independence) on Performance Assessment of Self‐Care Skills (PASS) Cognitively Mediated Instrumental Activities of Daily Living (C‐IADL), in individuals with amnestic mild cognitive impairment (aMCI). It aims to determine: (1) the associ...
Article
Introduction Both the DSM-5 and NIA-AA (Albert et al., 2011) stipulate methods for assessing and diagnosing cognitive decline but differ in their approach for estimating cognitive ability. The DSM suggests that evidence of cognitive decline is demonstrated either through culturally normed neuropsychological evaluation or through the use of “bedside...
Article
Neuropsychiatric symptoms (NPS) such as depression, apathy and agitation are common in neurocognitive disorders such as Alzheimer's disease (AD) and its prodrome, Mild Cognitive Impairment (MCI). Importantly, the presence of NPS is a prognostic indicator of future decline in MCI and AD and reduces quality of life in both patients and caregivers. Ph...
Article
Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural...
Conference Paper
Full-text available
Background: Both cognitive impairment and depression are associated with cardiovascular risk factors (CVRFs). CVRFs increase risk of cognitive decline and dementia in older adults. However, the extent to which these factors are associated with cognitive impairment in patients with mild neurocognitive disorder with and without a history of lifetime...
Article
BACKGROUND AND PURPOSE: Amyloid deposition, tau neurofibrillary tangles, and cerebrovascular dysfunction are important pathophysiologic features in Alzheimer's disease. Pittsburgh compound B ([11C]‐PIB) is a positron emission tomography (PET) radiotracer used to quantify amyloid deposition in vivo. In addition, certain models of [11C]‐PIB delivery...
Article
Full-text available
Introduction: Surgical treatment for patients with epilepsy who do not respond to antiepileptic medication can lead to changes in behavior, including new onset of neuropsychiatric symptoms such as depression and anxiety. In other cases, neuropsychiatric symptoms present before surgery may be alleviated. Because application of diagnostic criteria f...
Article
Background: Previous studies examining the link between neuropsychiatric symptoms (NPS) and biomarkers of Alzheimer's disease (AD) may be confounded by remitted or past history of psychiatric illness, which in itself is associated with AD biomarkers such as reduced medial temporal lobe (MTL) volume. Objective: We examined associations between mo...
Article
While several studies have found that neural oscillations play a key role in the functioning of working memory, the nature of aberrant oscillatory activity underlying working memory impairments in Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains largely unexplored. These individuals often display structural alterations in brain...
Conference Paper
Introduction Although cardiovascular risk factors (CVRFs) have been identified as important risk factors for both major depression and cognitive decline in later life, their association with neuropsychiatric symptoms (NPS) has not been fully elucidated. Furthermore, CVRFs, particularly hypertension, hypercholesterolemia, and diabetes, may ultimatel...
Conference Paper
Introduction Cardiovascular risk factors are associated with both cognitive impairment and depression. However, the extent to which these factors are associated with cognitive impairment in patients with mild neurocognitive disorder with and without a history of lifetime depression needs to be clarified. Methods We looked at the distribution of Fr...
Conference Paper
In the recently published National Institute on Aging and Alzheimer's Association (NIA-AA)’s Research Framework, the definition of Alzheimer's disease (AD) shifts from a syndromal to a biological entity, defined by underlying pathology as evidenced by the presence of AD biomarkers in vivo or on post-mortem examination (Jack et al., 2018, Alzheimers...
Article
Background:Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Objective:Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. Methods:We examined the...
Article
Background: Ketamine is known to rapidly reduce depressive symptoms and suicidal ideation (SI) in patients with major depressive disorder (MDD), but evidence is limited for its acceptability and effectiveness in "real-world" settings. This case series examines serial ketamine infusions in reducing SI and depression scores in adults with MDD admitt...
Article
Full-text available
Working memory deficits are common among individuals with Alzheimer’s dementia (AD) or mild cognitive impairment (MCI). Yet, little is known about the mechanisms underlying these deficits. Theta-gamma coupling—the modulation of high-frequency gamma oscillations by low-frequency theta oscillations—is a neurophysiologic process underlying working mem...
Article
Full-text available
Objective: Early and preferential targeting of limbic structures by Alzheimer disease (AD)-related pathology suggests emotion dysregulation may serve as a marker of AD risk. We studied emotional verbal memory in two groups at risk for AD, amnestic mild cognitive impairment (aMCI) and late-onset depression (LOD), to test the hypothesis that aMCI an...
Article
Full-text available
Objective: To evaluate the effect of depression on functional recovery in geriatric patients who have completed an inpatient rehabilitation program. Design: Prospective cohort study. Setting: University-affiliated multidisciplinary, high-tolerance, short-duration geriatric rehabilitation. Participants: Convenience sample of 65 patients [mean...
Article
Full-text available
Purpose of review: Stress exacerbates mental illnesses such as depression but also appears to increase risk of dementia, suggesting a common mechanism for development of stress-induced affective and cognitive impairment. The purpose of this review is to address the question of whether anxiety 'damages' the brain, and to identify potential mechanis...
Article
Full-text available
Background: The purpose of the current study was to test the hypothesis that anxiety in amnestic mild cognitive impairment (aMCI) increases rates of conversion to Alzheimer’s disease (AD), and to identify potential neural mechanisms underlying such an association. Methods: 376 participants with aMCI from the Alzheimer’s Disease Neuroimaging Initiat...
Article
Full-text available
Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as m...
Article
Full-text available
The aim of this study was to characterize the attitudes of older adults on an inpatient palliative care unit toward complementary and alternative medicine (CAM) therapies. A consecutive sample of 33 inpatients (61 to 98 years old) completed a questionnaire that examined their attitudes toward CAM to determine the acceptability of these therapies. C...
Article
Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to n...