Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage

Ranasinghe, Kamalini G.; Rankin, Katherine P.; Lobach, Iryna; Kramer, Joel H.; Sturm, Virginia E.; Bettcher, Brianne M.; Possin, Katherine L.; You, S. Christine; LaMarre, Amanda K.; Shany‐Ur, Tal; Stephens, Melanie; Perry, David C.; Lee, Suzee E.; Miller, Zachary A.; Gorno‐Tempini, Maria Luisa; Rosen, Howard J.; Boxer, Adam L.; Seeley, William W.; Rabinovici, Gil D.; Vossel, Keith A.; Miller, Bruce L.

doi:10.1212/wnl.0000000000002373

Cited by 91 publications

(99 citation statements)

References 46 publications

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“…Interestingly, language-based cognitive abilities, including semantic processing, was also associated with total immediate recall in this group. Although there is relative sparing of language networks in bvFTD, even early in the disease process, performances on confrontational naming and fluency differ from those of healthy controls (Ranasinghe et al, 2016; Seeley et al, 2008). These differences may represent true changes in semantic processing areas (e.g., anterior temporal lobe pathology; Rabinovici and Miller, 2010) that disrupt contextual integration of novel verbal information during immediate verbal recall.…”

Section: Discussionmentioning

confidence: 86%

Is “Learning” episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts

et al. 2017

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Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of “total learning” immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer’s disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1–4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps > 0.05). Multiple neurobehavioral systems are associated with “total learning” immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous.

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Section: Discussionmentioning

confidence: 86%

Is “Learning” episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts

et al. 2017

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“…Conversely, the severity of depression and elation were inversely correlated with the severity of functional impairment in bvFTD. Unlike apathy and aberrant motor activity, which progressively increase with worsening bvFTD [39], depression and elation remain stable or even decrease with disease progression [39,40]. These mood symptoms may be more prominent at milder stages of bvFTD, when functional impairments are less severe.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it is difficult to compare dementia severity across FTD subtypes, given their very different clinical presentations. We chose to use symptom duration as a potential surrogate; others have used the global Clinical Dementia Rating (CDR [41]) for this purpose [39,40]. The standard CDR was less well suited for our analyses, given its focus on AD symptomatology and inclusion of functional decline in its scoring.…”

Section: Discussionmentioning

confidence: 99%

Executive Dysfunction and Behavioral Symptoms Are Associated with Deficits in Instrumental Activities of Daily Living in Frontotemporal Dementia

Moheb

Mendez²,

Kremen³

et al. 2017

Dement Geriatr Cogn Disord

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Background: Deficits in instrumental activities of daily living (ADLs) may be more prominent in behavioral variant frontotemporal dementia (bvFTD) than in nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or semantic variant primary progressive aphasia (svPPA). It is uncertain whether frontotemporal dementia (FTD) subgroups exhibit different patterns and/or predictors of functional impairment. Methods: We examined data from participants diagnosed with bvFTD (n = 607), svPPA (n = 132), and nfvPPA (n = 155) who were included in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and assessed with the Functional Activities Questionnaire (FAQ). Stepwise multiple linear regression analyses were performed to identify associations between FAQ scores and cognitive/behavioral deficits using the NACC UDS neuropsychological testing battery and the Neuropsychiatric Inventory Questionnaire. Results: FAQ scores were higher in bvFTD than svPPA or nfvPPA. Functional deficits across FTD subtypes differed in severity, but not pattern, and were driven by executive dysfunction and behavioral symptoms. Conclusion: Executive dysfunction and behavioral symptoms underlie instrumental ADL deficits in FTD, which are most prominent in bvFTD.

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“…All AD patients underwent a battery of neuropsychological tests designed to assess major domains of cognition. The full battery of tests was detailed in previous reports (Kramer, et al, 2003,Ranasinghe, et al, 2016). We selected the cognitive domains that are primarily dependent on brain areas in close proximity to speech motor control network, specifically the frontal-temporal-parietal lobes, and prefrontal cortex, to examine their associations with the sensorimotor integration deficits detected from the pitch-perturbation experiment.…”

Section: Methodsmentioning

confidence: 99%

Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease

Ranasinghe

Gill

Kothare

et al. 2017

Neurobiology of Aging

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Speakers respond automatically and rapidly to compensate for brief perturbations of pitch in their auditory feedback. The specific adjustments in vocal output require integration of brain regions involved in speech-motor-control in order to detect the sensory-feedback-error and implement the motor-correction. Cortical regions involved in the pitch-reflex phenomenon are highly vulnerable targets of network disruption in Alzheimer's disease (AD). We examined the pitch-reflex in AD patients (n=19) compared to an age-matched control group (n=16). We measured the degree of behavioral compensation (peak-compensation) and the extent of the adaptive response (pitch-response-persistence). Healthy-controls reached a peak-compensation of 18.7±0.8 cents, and demonstrated a sustained compensation at 8.9±0.69 cents. AD patients, in contrast, demonstrated a significantly elevated peak-compensation (22.4±1.2 cents, P<0.05), and a reduced sustained response (pitch-response-persistence, 4.5±0.88 cents, P<0.001). The degree of increased peak-compensation predicted executive dysfunction, while the degree of impaired pitch-response-persistence predicted memory dysfunction, in AD patients. The current study demonstrates pitch-reflex as a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration, and compromised plasticity mechanisms of memory, in AD.

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Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage

Cited by 91 publications

References 46 publications

Is “Learning” episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts

Is “Learning” episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts

Executive Dysfunction and Behavioral Symptoms Are Associated with Deficits in Instrumental Activities of Daily Living in Frontotemporal Dementia

Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease

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