Ali Jannati

• MD PhD
• Director of Cognitive Science at Linus Health

Salient distractors delay visual search for less salient targets in additional-singleton tasks, even when the features of the stimuli are fixed across trials. According to the salience-driven selection hypothesis, this delay is due to an initial attentional deployment to the distractor. Recent event-related potential (ERP) studies found no evidence...

The presence of a salient distractor interferes with visual search. According to the salience-driven selection hypothesis, this interference is because of an initial deployment of attention to the distractor. Three event-related potential (ERP) findings have been regarded as evidence for this hypothesis: (a) salient distractors were found to elicit...

This study was conducted to evaluate the effect of simvastatin (40 mg/day) as an adjuvant therapy to interferon beta (IFNb 1a, 30 microg once weekly) in relapsing-remitting multiple sclerosis patients, compared with placebo. We enrolled 85 patients with relapsing-remitting multiple sclerosis (71% female) who were already receiving IFNb 1a (Avonex),...

INTRODUCTION While a limited number of disease‐modifying treatments for Alzheimer's disease (AD) have been approved in the United States, there is caution in adopting these treatments in clinical use. The electronic Person‐Specific Outcome Measure (ePSOM) tool was recently developed to establish whether, besides modifying underlying AD pathology, n...

Background Semantic memory refers to knowledge of attributes associated with common objects. Quantifying the strength of semantic association between successive ‘animal' fluency responses can be challenging. The current research assessed between‐group differences for ‘animal' fluency total output and selected verbal serial list learning, episodic m...

Background It is essential that both drug and lifestyle‐based interventions aimed at delaying the functional decline in conditions like Alzheimer’s disease and related dementias (ADRDs) capture change in functioning that incorporates the person’s voice. Such brain health priorities can vary across populations and it is unclear to what degree findin...

Background There is an urgent need for neuropsychological screening tests that are easily deployed and reliable. We have developed a digital neuropsychological screening protocol that is administered on a tablet, automatically scored using artificial intelligence, and requires approximately 10 minutes to administer. This tablet‐administered protoco...

Background Almost all primary care providers (PCPs) believe screening for mild cognitive impairment (MCI) and dementia in older patients is important. However, there are significant barriers in primary care, including low provider confidence in their assessment skills, time constraints, competing priorities, and poor financial incentives. Consequen...

Introduction Compelling evidence from longitudinal trials demonstrates that adopting certain lifestyles, especially in midlife to early late life, can reduce the risk of dementia, reduce the severity of the associated disability, and decrease progression to dementia in individuals with mild cognitive impairment by as much as 40%. The Life and Healt...

Background Digital neuropsychological assessment easily captures behavior previously not obtainable by traditional pencil‐and‐paper tests. Verbal serial list learning tests are commonly used to assess for putative neurogenerative syndromes. Recognition test performance is often expressed compiling simple ‘yes/ no' responses, but fail to assess proc...

Introduction Evaluation of functional dependence in activities of daily living (ADLs) and instrumental activities of daily living (iADLs) is necessary for dementia diagnosis. ADL and iADL questionnaires are typically employed, but with progressive cognitive impairment, a care partner must step in to assist with these tests, causing logistical burde...

Background It is essential that both drug and lifestyle‐based interventions aimed at delaying the functional decline in conditions like Alzheimer’s disease and related dementias (ADRDs) capture change in functioning that incorporates the person’s voice. Such brain health priorities can vary across populations and it is unclear to what degree findin...

Background A typical paper/pencil neuropsychological evaluation to assess for mild cognitive impairment (MCI) and dementia is lengthy. There is a need for a brief, digitally administered/scored neuropsychological protocol that can differentiate patients who are cognitively normal versus MCI and dementia. This need is particularly acute with the adv...

Background Mild cognitive impairment (MCI), is characterized by cognitive dysfunction not severe enough to affect one’s activities of daily living (ADLs)1. Annually, approximately 15‐20% adults 65 and older will present with MCI 1. MCI is considered a significant risk factor and a robust predictor for developing dementia. The time course for progre...

Background Disease‐modifying treatments for Alzheimer’s disease highlight the need for early detection of cognitive decline. However, most primary care providers do not currently perform routine cognitive testing, in part due to a lack of time and resources to administer and interpret the tests. Brief, self‐scoring, and sensitive digital cognitive...

Background Digital neuropsychological assessment easily captures behavior previously not obtainable by traditional pencil‐and‐paper tests. Verbal serial list learning tests are commonly used to assess for putative neurogenerative syndromes. Recognition test performance is often expressed compiling simple ‘yes/ no’ responses, but fail to assess proc...

Background Semantic memory refers to knowledge of attributes associated with common objects. Quantifying the strength of semantic association between successive ‘animal’ fluency responses can be challenging. The current research assessed between‐group differences for ‘animal’ fluency total output and selected verbal serial list learning, episodic m...

Background Maximizing the benefits of disease‐modifying treatments (DMTs) for Alzheimer’s disease (AD) requires early identification of cognitive impairment and abnormal brain amyloid‐beta (Aβ) status. Either one alone is insufficient. Additionally, clinical trials of DMTs are impeded by high screen failure rates and costly prescreening. Thus, an e...

Background Amnestic and vascular dementia are two common types of dementia. Currently, diagnosing and differentiating between these two conditions requires comprehensive neuropsychological testing, neuroimaging studies, and cerebrospinal fluid analysis. Identifying these conditions at early stages, i.e., mild cognitive impairment (MCI), is crucial...

Background Early detection of cognitive impairment is crucial for maximizing the benefits of disease‐modifying treatments for Alzheimer’s disease (AD). Brief, automatically‐scored digital cognitive assessments such as the Digital Clock and Recall (DCR) show promise in streamlining this early detection. However, wide adoption of such assessments in...

Background The Trail Making Test (TMT) is one of the tests most commonly included in neuropsychological batteries to assess executive functions. A digitized version of TMT would provide objective measurements of time to complete (TTC) and total number of errors (TE) with minimal training, and eventually enable process metrics including detailed eva...

Primary care providers currently wait for a complaint to initiate a ‘for-cause’ cognitive evaluation and often refer the patient to a specialist. Specialist evaluation then leads to the diagnosis, but treatment occurs late and is unlikely to meaningfully prevent or reduce disability. We hypothesized a brief digital cognitive assessment (DCA), the D...

Primary care providers currently wait for a complaint to initiate a ‘for-cause’ cognitive evaluation and often refer the patient to a specialist. Specialist evaluation then leads to the diagnosis, but treatment occurs late and is unlikely to meaningfully prevent or reduce disability. We hypothesized a brief digital cognitive assessment (DCA), the D...

It is estimated that 1 in 4 people worldwide will be living with hearing impairment by 2050. We propose a digital Speech Hearing Screener (dSHS) using short nonsense word recognition to measure speech-hearing ability. We compare dSHS outcomes with standardized pure-tone averages (PTA) and speech-recognition thresholds (SRT). 50 participants aged 55...

Background There is an urgent need for neuropsychological screening tests that are easily deployed and reliable. We have developed a digital neuropsychological screening protocol that is administered on a tablet, automatically scored using artificial intelligence, and requires approximately 10 minutes to administer. This tablet‐administered protoco...

Background Distinguishing between mild cognitive impairment (MCI) and early dementia requires both neuropsychological and functional assessment that often relies on caregivers’ insights. Contacting a patient's caregiver can be time-consuming in a physician's already-filled workday. Objective To assess the utility of a brief, machine learning (ML)-...

By 2050, 1 in 4 people worldwide will be living with hearing impairment. We propose a digital Speech Hearing Screener (dSHS) using short nonsense word recognition to measure speech-hearing ability. The importance of hearing screening is increasing due to the anticipated increase in individuals with hearing impairment globally. We compare dSHS outco...

Introduction Alzheimer’s disease and related dementias (ADRD) represent a substantial global public health challenge with multifaceted impacts on individuals, families, and healthcare systems. Brief cognitive screening tools such as the Mini-Cog© can help improve recognition of ADRD in clinical practice, but widespread adoption continues to lag. We...

Background Dual task paradigms are thought to offer a quantitative means to assess cognitive reserve and the brain’s capacity to allocate resources in the face of competing cognitive demands. The most common dual task paradigms examine the interplay between gait or balance control and cognitive function. However, gait and balance tasks can be physi...

Introduction A rapid and reliable neuropsychological protocol is essential for the efficient assessment of neurocognitive constructs related to emergent neurodegenerative diseases. We developed an AI-assisted, digitally administered/scored neuropsychological protocol that can be remotely administered in ~10 min. This protocol assesses the requisite...

Digital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital...

Incorporating person-centered outcomes into clinical trials for neurodegenerative diseases has been challenging due to a deficiency in quantitative measures. Meanwhile, the integration of personally meaningful treatment targets in clinical practice remains qualitative, failing to truly inform evaluations, therapeutic interventions and longitudinal...

Background Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making...

Background By 2050, 1 in 4 people worldwide will be living with hearing impairment by 2050. We propose a digital Speech Hearing Screener (dSHS) using short nonsense word recognition to measure speech-hearing ability. We compare dSHS outcomes with standardized pure-tone averages (PTA) and speech-recognition thresholds (SRT). 50 participants (aged 55...

Digital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital...

INTRODUCTION: Early detection of Alzheimer’s disease and cognitive impairment is critical to improving the healthcare trajectories of aging adults, enabling early intervention and potentially prevention of decline. METHODS: To evaluate multi-modal feature sets for assessing memory and cognitive impairment, feature selection and subsequent logistic...

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptat...

Background Disease-modifying treatments for Alzheimer’s disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the test...

Background It is essential both drug and lifestyle‐based interventions aimed to delay the onset of advanced cognitive decline deliver a meaningful outcome for the patient. In the early stages of Alzheimer’s disease and related dementias (ADRDs), patient‐reported outcome (PRO) measures should be used in parallel with biological investigations of ADR...

Background Digital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assess...

Background Nearly 6.7 million people aged 65 and older in the US are living with Alzheimer’s disease (AD). Early detection of dementia presents a difficult challenge, as the earliest signs of cognitive decline often go undetected. Thus, more sensitive and clinically meaningful cognitive screening tools are needed. Evaluating the patient’s dependenc...

Background Early detection of Mild Cognitive Impairment (MCI) and Alzheimer’s Disease and Related Dementias (ADRD) is key to optimal management. Digital tests allow for the reliable capture of meaningful, process‐based neuropsychological test parameters that traditional paper/pencil measures fail to detect, thus enabling earlier detection. We asses...

Background DCTclock™ is an AI‐enabled digital cognitive assessment (DCA) that strongly discriminates between cognitively impaired and unimpaired individuals (receiver operating area under‐the‐curve AUC = 0.89). Among cognitively unimpaired individuals, DCTclock predicts greater PET Aβ burden and shows stronger discrimination (Cohen’s d = 0.76) betw...

Background Digital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic p...

Background Digital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclock TM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic...

Background Digital cognitive assessment solutions can overcome some barriers to cognitive screening in primary care by providing rapidly‐obtained objective insights without requiring specialty‐trained examiners. The Linus Health Digital Clock and Recall (DCR™) is a three‐part test consisting of three‐word immediate verbal acquisition, the Digital C...

Background Digital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assess...

Background Distinguishing mild cognitive impairment (MCI) and Alzheimer’s disease‐related dementia (ADRD) requires assessing the clinical impact of cognitive deficits on a patient’s activities of daily living. To accurately monitor cognitive decline, it is thus critical to combine early screening of cognitive deficits with the assessment of functio...

Purpose Motor evoked potential (MEP) amplitude and latency are acquired routinely during neuronavigated transcranial magnetic stimulation, a method of functional mapping of the motor cortex before epilepsy surgery. Although MEP amplitude is routinely used to generate a motor map, MEP latency in patients with focal epilepsy has not been studied syst...

BACKGROUND Dual task paradigms are thought to offer a quantitative means to assess cognitive reserve and the brain’s capacity to allocate resources in the face of competing cognitive demands. The most common dual task paradigms examine the interplay between gait or balance control and cognitive function. However, gait and balance tasks can be physi...

Dementia is a growing socioeconomic and medical problem that affects increasing portions of the population, with a prevalence that doubles every 5 years after the age of 65. Alzheimer’s disease (AD; 60–80%) and frontotemporal lobar degeneration (FTLD; 5–10%) constitute two of the most common causes of dementia. The first symptoms appear during an i...

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in ad...

Traumatic brain injury (TBI) increases cerebral reactive oxygen species production, which leads to continuing secondary neuronal injury after the initial insult. Cortical parvalbumin-positive interneurons (PVIs; neurons responsible for maintaining cortical inhibitory tone) are particularly vulnerable to oxidative stress and are thus disproportionat...

Neuronavigated transcranial magnetic stimulation (nTMS) has emerged as a presurgical language mapping tool distinct from the widely used functional magnetic resonance imaging (fMRI). We report fMRI and nTMS language‐mapping results in 19 pediatric‐epilepsy patients and compare those to definitive testing by electrical cortical stimulation, Wada tes...

In this piece, we raise the topic of universal cognitive screening for older adults. Dementia is the leading cause of disability, individual struggles, family challenges, and greater societal costs. We argue that universal screening for cognitive impairment among all individuals aged 65 and above has several important benefits: (1) Early diagnosis...

Background Many patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10Hz and intermittent theta-burst stimulation (iTBS) protocols. Methods T...

The salience-driven selection theory is comprised of three main tenets: (a) the most salient stimulus within a monitored region of the visual field captures attention, (b) the only way to prevent salience-driven distraction is by narrowly focusing attention elsewhere, and (c) all other goal-driven processes are possible only after the most salient...

Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation ( plasticity ) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well define...

Objective This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. Methods Authors of previously published studies were contacted and...

Background Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability des...

Objective To test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. Methods 44 adult neurotypical (NT) participa...

Objective Interindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of fac...

Objective: In this study we examined the personality profiles of adults with autism spectrum disorder (ASD) using a standard personality test. In addition, we investigated the association between ASD-related face memory deficits (FMD) and theory of mind (ToM). In a broader context, we examine whether there are distinct clinical phenotypes in the AS...

Objective Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained...

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological...

Background Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective /Hypothesis: This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboratio...

A range of scalp electroencephalogram (EEG) abnormalities correlates with the core symptoms of autism spectrum disorder (ASD). Among these are alterations of brain oscillations in the gamma‐frequency EEG band in adults and children with ASD, whose origin has been linked to dysfunctions of inhibitory interneuron signaling. While therapeutic interven...

Objective. To assess the utility of the modulation of motor cortex (M1) excitability by continuous theta-burst stimulation (cTBS) as a physiologic biomarker for adults with autism spectrum disorder (ASD), and to evaluate the influences of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms on cTBS aftereffects. Method...

Objectives: A neurophysiologic biomarker for autism spectrum disorder (ASD) is highly desirable and can improve diagnosis, monitoring, and assessment of therapeutic response among children with ASD. We investigated the utility of continuous theta-burst stimulation (cTBS) applied to the motor cortex (M1) as a biomarker for children and adolescents w...

To assess motor cortex neurophysiology, including the mechanisms of neuroplasticity, transcranial magnetic stimulation (TMS) is typically applied to the motor "hotspot"- the optimal site for inducing a twitch in a given target muscle. It is known that the effects of suprathreshold repetitive TMS (rTMS) spread along functional connections beyond the...

Objectives The utility of continuous theta-burst stimulation (cTBS) as index of cortical plasticity is limited by inadequate characterization of its test–retest reliability. We thus evaluated the reliability of cTBS aftereffects, and explored the roles of age and common single-nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF)...

The default-mode network (DMN) is affected by advancing age, where particularly long-range connectivity has been consistently reported to be reduced as compared to young individuals. We examined whether there were any differences in the effects of intermittent theta-burst stimulation (iTBS) in DMN connectivity between younger and older adults, its...

The pulse waveform and current direction of transcranial magnetic stimulation (TMS) influence its interactions with the neural substrate; however, their role in the efficacy and reliability of single- and paired-pulse TMS measures is not fully understood. We investigated how pulse waveform and current direction affect the efficacy and test-retest r...

Background: Exercise-mediated cognitive improvements can be at least partly attributed to neuroplastic changes in the nervous system, and may be influenced by the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene. Transcranial magnetic stimulation (TMS) can be used to assess mechanisms of plasticity in humans noninvasively...

Objective: We used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS). Methods: 21 healthy adults (age±SD, 36.9±15.2years) underwent cTBS of left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5-50min post-cTBS (T5-T50) were calculat...

Background: Transcranial magnetic stimulation (TMS) can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD) increases, it is critical to understand their reproducibility (i.e., test–retest reliability) in the populat...

Objective: Identify the optimal number of pulses necessary to achieve reliable measures of motor evoked potentials (MEPs) in transcranial magnetic stimulation (TMS) studies. Methods: Retrospective data was obtained from 54 healthy volunteers (30 men, mean age 61.7±13.1years) who as part of prior studies had completed three blocks of 30 consecuti...

Stroke is a leading cause of disability among adults. Existing rehabilitation programs haven’t been able to accomplish full motor recovery partially due to the pathologic plasticity exerted from the unaffected hemisphere to the affected one. This inhibition can be disrupted using non-invasive brain stimulation (NIBS). Transcranial magnetic stimulat...