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Book: Dementia

Graff-Radford, Neill R.

(Neurologic clinics ; 25,3)

2007

Author's details	guest ed. Neill R. Graff-Radford
Series title	Neurologic clinics ; 25,3
Collection
Language	English
Size	XII S., S. 577 - 865 : Ill., graph. Darst.
Publisher	Saunders
Publishing place	Philadelphia u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT015275620
ISBN	1-4160-5092-2 ; 978-1-4160-5092-6
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Is normal pressure hydrocephalus becoming less idiopathic?

Graff-Radford, Neill R

Neurology

2016 Volume 86, Issue 7, Page(s) 588–589

MeSH term(s)	Brain/diagnostic imaging ; Female ; Humans ; Hydrocephalus, Normal Pressure/diagnostic imaging ; Hydrocephalus, Normal Pressure/epidemiology ; Male ; Radiography ; Vascular Diseases/epidemiology
Language	English
Publishing date	2016-02-16
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000002377
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Article ; Online: Senile plaque-associated transactive response DNA-binding protein 43 in Alzheimer's disease: A case report spanning 16 years of memory loss.

Carlos, Arenn F / Koga, Shunsuke / Graff-Radford, Neill R / Baker, Matthew C / Rademakers, Rosa / Ross, Owen A / Dickson, Dennis W / Josephs, Keith A

Neuropathology : official journal of the Japanese Society of Neuropathology

2023 Volume 44, Issue 2, Page(s) 115–125

Abstract: Transactive response DNA-binding protein 43 (TDP-43) pathological inclusions are found in frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer's disease (AD-TDP). While clinically different, TDP-43 inclusions in FTLD-TDP and AD can have similar ... ...

Abstract	Transactive response DNA-binding protein 43 (TDP-43) pathological inclusions are found in frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer's disease (AD-TDP). While clinically different, TDP-43 inclusions in FTLD-TDP and AD can have similar morphological characteristics. However, TDP-43 colocalizing with tau and forming "apple-bite" or "flame-shaped" neuronal cytoplasmic inclusions (NCI) are only found in AD-TDP. Here, we describe a case with AD and neuritic plaque-associated TDP-43. The patient was a 96-year-old right-handed Caucasian woman who had developed a slowly progressive amnestic syndrome compatible with typical AD at age 80. Genetic testing revealed APOE ε3/ε4, GRN r5848 CT, and MAPT H1/H2 genotype. Consistent with the old age at onset and long disease duration, limbic-predominant AD was found at autopsy, with high hippocampal yet low cortical neurofibrillary tangle (NFT) counts. Hippocampal and amygdala sclerosis were present. Immunohistochemistry for phospho-TDP-43 showed NCIs, dystrophic neurites, and rare neuronal intranuclear inclusions consistent with FTLD-TDP type A, as well as tau NFT-associated TDP-43 inclusions. These were frequent in the amygdala, entorhinal cortex, hippocampus, occipitotemporal gyrus, and inferior temporal gyrus but sparse in the mid-frontal cortex. Additionally, there were TDP-43-immunoreactive inclusions forming plaque-like structures in the molecular layer of the dentate fascia of the hippocampus. The presence of neuritic plaques in the same region was confirmed using thioflavin-S fluorescent microscopy and immunohistochemistry for phospho-tau. Double labeling immunofluorescence showed colocalization of TDP-43 and tau within neuritic plaques. Other pathologies included mild Lewy body pathology predominantly affecting the amygdala and olfactory bulb, aging-related tau astrogliopathy, and mixed small vessel disease (arteriolosclerosis and amyloid angiopathy) with several cortical microinfarcts. In conclusion, we have identified TDP-43 colocalizing with tau in neuritic plaques in AD, which expands the association of TDP-43 and tau in AD beyond NFTs. The clinical correlate of this plaque-associated TDP-43 appears to be a slowly progressive amnestic syndrome.
MeSH term(s)	Female ; Humans ; Aged, 80 and over ; Alzheimer Disease/pathology ; Plaque, Amyloid ; Frontotemporal Dementia ; Frontotemporal Lobar Degeneration/pathology ; DNA-Binding Proteins/metabolism ; Memory Disorders/etiology
Chemical Substances	DNA-Binding Proteins
Language	English
Publishing date	2023-07-31
Publishing country	Australia
Document type	Case Reports
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12938
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Article ; Online: Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus.

Graff-Radford, Neill R

Neurology

2014 Volume 83, Issue 17, Page(s) 1573–1575

Abstract: Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD).: Methods: We describe NPH CSF biomarkers and how shunt surgery ... ...

Abstract	Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD). Methods: We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings. Results: In NPH, β-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently. Conclusions: In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD.
MeSH term(s)	Alzheimer Disease/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Humans ; Hydrocephalus, Normal Pressure/cerebrospinal fluid ; Hydrocephalus, Normal Pressure/diagnosis ; Peptide Fragments/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; amyloid beta-protein (1-42) ; tau Proteins
Language	English
Publishing date	2014-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000000916
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Article ; Online: Normal Pressure Hydrocephalus.

Graff-Radford, Neill R / Jones, David T

Continuum (Minneapolis, Minn.)

2019 Volume 25, Issue 1, Page(s) 165–186

Abstract: Purpose of review: Since it was first described in 1965, normal pressure hydrocephalus (NPH) has been a controversial subject. New studies have shed light on its epidemiology and pathogenesis and provided objective ways to measure outcome in patients ... ...

Abstract	Purpose of review: Since it was first described in 1965, normal pressure hydrocephalus (NPH) has been a controversial subject. New studies have shed light on its epidemiology and pathogenesis and provided objective ways to measure outcome in patients with NPH. Neuroimaging has improved and allows better recognition of both NPH and the presence of overlapping diseases RECENT FINDINGS: Several recent epidemiologic studies confirm that NPH is a rare disease, but the presence of large ventricles is a common finding with aging. NPH may be multifactorial, including congenital causes, vascular disease, and impaired CSF absorption. MRI features of NPH include enlarged ventricular size and CSF fluid collection outside the ventricles not due to atrophy. The term disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been used to describe prognostic MRI features in NPH, including a "tight high convexity" and enlargement of CSF spaces in the sylvian fissure. DESH has been included in the Japanese guideline for the diagnosis and treatment of NPH. A new NPH scale has been published that provides an objective framework for evaluating patients with NPH before and after shunt placement. Programmable shunts can noninvasively manage overdrainage complications. Surgical outcome has been improving over time. Recent studies have led to improved recognition of overlapping diseases such as Alzheimer pathology, which co-occurs in about 30% of NPH cases. Fludeoxyglucose positron emission tomography (FDG-PET) is a promising imaging modality for diagnosing NPH and detecting concomitant degenerative disease. Summary: A systematic approach to patients with possible NPH allows recognition of the subset of patients who will respond to shunt surgery and identification of those with alternative diagnoses.
MeSH term(s)	Atrophy/diagnosis ; Atrophy/pathology ; Brain/pathology ; Humans ; Hydrocephalus, Normal Pressure/diagnosis ; Hydrocephalus, Normal Pressure/etiology ; Magnetic Resonance Imaging/methods ; Prognosis ; Risk Factors
Language	English
Publishing date	2019-02-17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000000689
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Article ; Online: Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

Lachner, Christian / Craver, Emily C / Babulal, Ganesh M / Lucas, John A / Ferman, Tanis J / White, Richard O / Graff-Radford, Neill R / Day, Gregory S

Annals of neurology

2024 Volume 95, Issue 3, Page(s) 518–529

Abstract: Objective: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging.: Methods: ... ...

Abstract	Objective: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. Methods: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. Results: Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (β = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (β = 2.65, 95% CI = 0.38-4.91, p = 0.023). Interpretation: Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.
MeSH term(s)	Humans ; Alzheimer Disease/complications ; Black or African American ; Cognition Disorders/etiology ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/complications ; Risk Factors ; White
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26847
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Article ; Online: Prevention of late‑life dementia: what works and what does not.

Tipton, Philip W / Graff-Radford, Neill R

Polish archives of internal medicine

2018 Volume 128, Issue 5, Page(s) 310–316

Abstract: Advances in the treatment and prevention of disease have contributed to an aging global population. Subsequently, there is an increasing prevalence of age‑related conditions, such as dementia. There are currently no disease‑modifying therapies ... ...

Abstract	Advances in the treatment and prevention of disease have contributed to an aging global population. Subsequently, there is an increasing prevalence of age‑related conditions, such as dementia. There are currently no disease‑modifying therapies commercially available, and there is a growing emphasis on strategies to prevent dementia. We have reviewed the relevant literature pertaining to dementia risk and putative prevention factors. We present our findings by summarizing the pertinent items that may play a role in prevention and conclude our recommendations at this time.
MeSH term(s)	Alzheimer Disease/epidemiology ; Alzheimer Disease/prevention & control ; Dementia/epidemiology ; Dementia/prevention & control ; Female ; Humans ; Life Style ; Male ; Risk
Language	English
Publishing date	2018-05-16
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.4263
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Article ; Online: Can aerobic exercise protect against dementia?

Graff-Radford, Neill R

Alzheimer's research & therapy

2011 Volume 3, Issue 1, Page(s) 6

Abstract: There are more than 36 million people in the US over the age of 65, and all of them are impacted by the cognitive decline and brain atrophy associated with normal aging and dementia-causing conditions like Alzheimer's disease, Lewy body disease, and ... ...

Abstract	There are more than 36 million people in the US over the age of 65, and all of them are impacted by the cognitive decline and brain atrophy associated with normal aging and dementia-causing conditions like Alzheimer's disease, Lewy body disease, and vascular dementia. Recently, moderate exercise and improved fitness have been shown to enhance cognition in cognitively normal older persons as well as in individuals who complain of memory difficulty. Additionally, fitness correlates with brain volume in persons who are cognitively normal and those with Alzheimer's disease. Exercise in mouse models causes neurogenesis in the dentate gyrus. This review will discuss animal experiments, epidemiology, limited prospective studies, and biomarker data that make the case that prospective blinded studies are urgently needed to evaluate the role of aerobic exercise in protecting against dementia.
Language	English
Publishing date	2011-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/alzrt65
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Article ; Online: Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging.

Nissim, Nicole R / Fudge, Michelle R / Lachner, Christian / Babulal, Ganesh M / Allyse, Megan A / Graff-Radford, Neill R / Lucas, John A / Day, Gregory S

Journal of racial and ethnic health disparities

2023

Abstract: Background: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and ... ...

Abstract	Background: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases. Study design: Survey respondents (n = 240) rated barriers and facilitators of research participation. Age-specific differences were evaluated using nonparametric Kruskal-Wallis tests across respondents aged 18-44 years (n = 76), 45-64 years (n = 83), and ≥ 65 years (n = 81). Strategies to mitigate barriers and promote facilitators were further explored via community-based focus groups. Pooled frequency of common themes discussed in focus groups were evaluated and compared across different ages including ≥ 45 years, ≥ 65 years, and mixed ages ≥ 45 years. Results: Younger respondents (aged 18-44 and 45-64 years) expressed a greater need for flexibility in when, where, and how research testing takes place versus adults ≥ 65 years. Focus groups emphasized long-lasting consequences of systemic racism and the need to build and foster trust to resolve barriers and promote research engagement amongst African Americans. Discussion: Age-specific strategies are needed to increase engagement, address recruitment disparities, and promote retention of African American participants in memory and aging studies across the lifespan.
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2760524-3
ISSN	2196-8837 ; 2197-3792
ISSN (online)	2196-8837
ISSN	2197-3792
DOI	10.1007/s40615-023-01741-z
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Article ; Online: Sagittal Spinal Deformity in Patients with Idiopathic Normal Pressure Hydrocephalus.

Lenartowicz, Karina A / Naylor, Ryan M / Mikula, Anthony L / Graff-Radford, Jonathan / Jones, David T / Cutsforth-Gregory, Jeremy K / Graff-Radford, Neill R / Fogelson, Jeremy L / Cogswell, Petrice M / Elder, Benjamin D

Turkish neurosurgery

2023 Volume 33, Issue 3, Page(s) 471–476

Abstract: Aim: To measure the baseline spinopelvic parameters and characterize the sagittal, and coronal plane deformities in patients with idiopathic normal pressure hydrocephalus (iNPH).: Material and methods: We analyzed a series of patients at one academic ...

Abstract	Aim: To measure the baseline spinopelvic parameters and characterize the sagittal, and coronal plane deformities in patients with idiopathic normal pressure hydrocephalus (iNPH). Material and methods: We analyzed a series of patients at one academic institution who underwent ventriculoperitoneal shunting for iNPH with pre-shunt standing full length x-rays. The series of patients was enrolled consecutively to minimize selection bias. We quantified comorbid sagittal plane spinal deformity based on the Scoliosis Research Society-Schwab classification system by assessing pelvic incidence and lumbar lordosis mismatch (PI-LL), pelvic tilt (PT), and sagittal vertical axis (SVA). Results: Seventeen patients (59% male) were included in this study. Mean (± standard deviation) age was 74 ± 5.3 years with a body mass index (BMI) of 30 ± 4.5 kg/m < sup > 2< sup > . Six patients (35%) had marked sagittal plane spinal deformity by at least one parameter: five (29%) had greater than 20˚ PI-LL mismatch, three (18%) had > 9.5 cm SVA, and one (6%) had PT greater than 30˚. Additionally, the thoracic kyphosis exceeded the lumbar lordosis in nine patients (53%). Conclusion: Positive sagittal balance, with thoracic kyphosis exceeding lumbar lordosis, is common in iNPH patients. This may lead to postural instability, especially in patients whose gait does not improve following shunting. These patients may warrant further investigation and workup, including full length standing x-rays. Future studies should assess for improvement in the sagittal plane parameters following shunt placement.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Hydrocephalus, Normal Pressure ; Kyphosis ; Lordosis ; Lumbar Vertebrae ; Quality of Life ; Retrospective Studies ; Scoliosis ; Spine/abnormalities
Language	English
Publishing date	2023-03-13
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	1203779-5
ISSN	2651-5032 ; 1019-5149
ISSN (online)	2651-5032
ISSN	1019-5149
DOI	10.5137/1019-5149.JTN.36555-22.3
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