Design and Verbal Fluency in Alzheimer’s Disease and Frontotemporal Dementia: Clinical and Metabolic Correlates

Abstract Objective: Cognitive processes underlying verbal and design fluency, and their neural correlates in patients with Alzheimer’s disease (AD) and behavioural variant Frontotemporal Dementia (bvFTD) remain unclear. We hypothesised that verbal and design fluency may be associated with distinct neuropsychological processes in AD and FTD, showing different patterns of impairment and neural basis. Methods: We enrolled 142 participants including patients with AD (n = 80, mean age = 74.71), bvFTD (n = 34, mean age = 68.18), and healthy controls (HCs) (n = 28, mean age = 71.14), that underwent cognitive assessment and 18F-fluorodeoxyglucose positron emission tomography imaging. Results: Semantic and phonemic fluency showed the largest effect sizes between groups, showing lower scores in bvFTD than AD and HCs, and lower scores in AD than HC. Both AD and bvFTD showed a lower number of unique designs in design fluency in comparison to HC. Semantic fluency was correlated with left frontotemporal lobe in AD, and with left frontal, caudate, and thalamus in bvFTD. Percentage of unique designs in design fluency was associated with the metabolism of the bilateral fronto-temporo-parietal cortex in AD, and the bilateral frontal cortex with right predominance in bvFTD. Repetitions in AD were correlated with bilateral frontal, temporal, and parietal lobes, and with left prefrontal cortex in bvFTD. Conclusions: Our findings demonstrate differential underlying cognitive processes in verbal and design fluency in AD and bvFTD. While memory and executive functioning associated with fronto-temporo-parietal regions were key in AD, attention and executive functions correlated with the frontal cortex and played a more significant role in bvFTD during fluency tasks.

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Accuracy of neuropsychological tests and the Neuropsychiatric Inventory in differential diagnosis between Frontotemporal dementia and Alzheimer's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-57642009dn30400012 ◽

2009 ◽

Vol 3 (4) ◽

pp. 332-336 ◽

Cited By ~ 2

Author(s):

Valéria Santoro Bahia ◽

Rene Viana

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differential Diagnosis ◽

Frontotemporal Dementia ◽

Neuropsychological Tests ◽

Motor Behavior ◽

Digit Span ◽

Semantic Fluency ◽

Neuropsychiatric Inventory ◽

Delayed Recall

Abstract The differential diagnosis between frontotemporal dementia (FTD) and Alzheimer's disease (AD) is sometimes difficult. Objectives: To verify the accuracy of neuropsychological tests and a behavioral disorders scale in the differential diagnosis between FTLD and AD. Methods: Retrospective data on 12 FTD patients and 12 probable AD patients were analyzed. The scores on neuropsychological tests (MMSE score, reverse digit span, delayed recall for drawings, semantic fluency of animals) and the Neuropsychiatric Inventory (NPI) in both groups were compared. Results: Both groups had similar performance on neuropsychological tests. All FTD patients and 50% of AD patients had neuropsychiatric abnormalities. The NPI score was 58.0±19.3 for the FTD patients, and 3.6±4.7 for the AD patients (p<0.01). Using a NPI cut-off score of 13, the sensitivity and specificity were 100% in this sample. The four most common neuropsychiatric disturbances in FTD patients were: apathy, aberrant motor behavior, disinhibition and eating abnormalities. Apathy and dysphoria/depression were the most common behavioral symptoms among the AD patients. Conclusions: In this study, NPI was found to be a useful tool for the differential diagnosis between FTD and AD. The neuropsychological tests commonly used in the medical office were unable to distinguish between the two groups.

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Distinct social-behavioral changes in frontotemporal dementia and early onset Alzheimer's disease

PsycEXTRA Dataset ◽

10.1037/e536722014-001 ◽

2014 ◽

Author(s):

Joseph P. Barsuglia ◽

Michelle J. Mather ◽

Hemali V. Panchal ◽

Aditi Joshi ◽

Elvira Jimenez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Early Onset ◽

Behavioral Changes ◽

Early Onset Alzheimer’S Disease

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Comparison of polysomnographic variables and their relationship to cognitive impairment in patients with Alzheimer's disease and frontotemporal dementia

Pharmacopsychiatry ◽

10.1055/s-0031-1292511 ◽

2011 ◽

Vol 44 (06) ◽

Author(s):

B Kundermann ◽

A Thum ◽

R Rocamora ◽

A Haag ◽

J-C Krieg ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Frontotemporal Dementia

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Tau Oligomer Induced HMGB1 Release Contributes to Cellular Senescence and Neuropathology Linked to Alzheimer's Disease and Frontotemporal Dementia

SSRN Electronic Journal ◽

10.2139/ssrn.3753798 ◽

2020 ◽

Author(s):

Sagar Gaikwad ◽

Nicha Puangmalai ◽

Alice Bittar ◽

Mauro Montalbano ◽

Stephanie Garcia ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Cellular Senescence

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Death Rate Due to COVID-19 in Alzheimer’s Disease and Frontotemporal Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-200940 ◽

2020 ◽

Vol 78 (2) ◽

pp. 537-541

Author(s):

Jordi A. Matias-Guiu ◽

Vanesa Pytel ◽

Jorge Matías-Guiu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Death Rate ◽

Case Series ◽

Care Homes ◽

Relevant Factor ◽

Increased Risk ◽

Care Facilities ◽

Probability Of Death

We aimed to evaluate the frequency and mortality of COVID-19 in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We conducted an observational case series. We enrolled 204 patients, 15.2% of whom were diagnosed with COVID-19, and 41.9% of patients with the infection died. Patients with AD were older than patients with FTD (80.36±8.77 versus 72.00±8.35 years old) and had a higher prevalence of arterial hypertension (55.8% versus 26.3%). COVID-19 occurred in 7.3% of patients living at home, but 72.0% of those living at care homes. Living in care facilities and diagnosis of AD were independently associated with a higher probability of death. We found that living in care homes is the most relevant factor for an increased risk of COVID-19 infection and death, with AD patients exhibiting a higher risk than those with FTD.

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Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00752-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Adeline Su Lyn Ng ◽

Juan Wang ◽

Kwun Kei Ng ◽

Joanna Su Xian Chong ◽

Xing Qian ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Network Topology ◽

Neuropsychiatric Symptoms ◽

Brain Network ◽

Salience Network ◽

Behavioral Variant Frontotemporal Dementia ◽

Control Networks ◽

And Control

Abstract Background Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits. Methods In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. Results Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. Conclusions Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.

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The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

Nature Communications ◽

10.1038/s41467-021-25060-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Patricia Yuste-Checa ◽

Victoria A. Trinkaus ◽

Irene Riera-Tur ◽

Rahmi Imamoglu ◽

Theresa F. Schaller ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Progression ◽

Frontotemporal Dementia ◽

Brain Regions ◽

Model System ◽

Cellular Model ◽

Tau Pathology ◽

Extracellular Chaperone ◽

Tau Aggregate

AbstractSpreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology.

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Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer’s disease: a systematic review of symptom-general and –specific lesion patterns

Molecular Neurodegeneration ◽

10.1186/s13024-021-00456-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yaojing Chen ◽

Mingxi Dang ◽

Zhanjun Zhang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Neuropsychiatric Symptoms ◽

Onset Time ◽

Anterior Cingulate ◽

Neural Basis ◽

Preclinical Ad ◽

Disease Stages ◽

Mild Cognitive Impairment Stage

AbstractNeuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

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