Publications by authors named "Joel H. Kramer"

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

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Objective: The 2024 Alzheimer's Association (AA) research diagnostic criteria for Alzheimer's Disease (AD) considers fluid biomarkers, including promising blood-based biomarkers for detecting AD. This study aims to identify dementia subtypes and their cognitive and neuroimaging profiles in older adults with dementia in the Democratic Republic of Congo (DRC) using biomarkers and clinical data.

Methods: Forty-five individuals with dementia over 65 years old were evaluated using the Community Screening Instrument for Dementia and the informant-based Alzheimer's Questionnaire.

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Introduction: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID).

Methods: Four independent cohorts were examined.

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Introduction: Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.

Methods: MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included.

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This study aimed to compare objective circadian rest-activity-rhythm (RAR) measures with self-reported circadian behavior and morning-evening preference in cognitively healthy older men and women. A total of 129 participants (ages 65-90) completed the Horne & Ostberg Morning-Eveningness Questionnaire (MEQ) and the Circadian Type Inventory (CTI) to assess their morning-evening preference and circadian traits, including rigidity, vigor, languidness, and flexibility. These subjective measures were compared to objective actigraphy data from a sub-cohort of 70 individuals who wore actigraphy watches for 24 hours a day over a 7-day period.

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Background: Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations.

Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid- (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor (TNFα) in Congolese adults with and without dementia.

Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included.

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  • Aberrant angiogenesis may contribute to cognitive decline and could serve as a therapeutic target for dementia prevention, though most prior studies have focused on animal models.
  • This study evaluated the relationship between blood markers of angiogenesis and cognitive aging in a sample of 435 older adults, revealing significant associations that varied by sex, particularly in younger women compared to men.
  • Results indicated that higher levels of certain angiogenic markers were linked to better executive function and less brain atrophy, suggesting the potential for targeting angiogenesis in addressing age-related cognitive impairment.
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Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

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Reward processing involves evaluation of stimuli to inform what an individual works to pursue or avoid. Patients with behavioral variant frontotemporal dementia (bvFTD) often display reward processing changes, including insensitivity to aversive stimuli. It is unknown how early in the disease course reward changes are detectable.

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  • The human face is essential for expressing emotions and social interaction, but the brain's structural connections to these facial expressions are still unclear.
  • A study of 55 older adults linked specific facial behaviors, like frowning or smiling during emotional videos, to increased gray matter volume in brain regions associated with emotional and motor functions.
  • The results indicate that both emotional and motor brain networks physically represent facial expressions, highlighting the midcingulate cortex's role in coordinating these facial movements during emotions.
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  • Moral decisions often involve tough choices where sometimes helping many people means harming a few.
  • Most research shows that being utilitarian (choosing the most good for the most people) can mean being less sensitive to others' feelings.
  • A study of a person with a brain issue showed they still made selfless choices that helped others, suggesting not everyone with this condition is unfriendly.
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Objective: The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias-amyloid-β (Aβ42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)-to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC).

Methods: Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer's Questionnaire (AQ).

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  • - Cardiovascular health, evaluated through Life's Simple 7 (LS7), is linked to slower cognitive decline and better brain integrity in patients with autosomal dominant frontotemporal lobar degeneration (FTLD).
  • - A study involving 247 FTLD genetic variant carriers and 189 non-carrier controls found that those with better cardiovascular health had slower memory and language declines, as well as less accumulation of frontal white matter hyperintensities (WMHs).
  • - Maintaining good cardiovascular health could be a key modifiable strategy to improve cognitive outcomes and brain health in individuals at risk for genetic forms of dementia.
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Background: Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations.

Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia.

Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included.

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  • Some sports and repeated head injuries (like playing football) might lead to brain problems later in life, especially conditions like Frontotemporal Dementia (FTD) and Primary Progressive Aphasia (PPA).
  • Researchers compared people with FTD/PPA to healthy ones to see how many had Traumatic Brain Injuries (TBI) and head impacts.
  • They found that people with FTD/PPA had more sports experience causing head impacts, and those with a history of head injuries had symptoms show up earlier than those without.
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Subjective cognitive concerns (SCC) are common even in cognitively normal older adults who lack objectively-detectable deficits on standard neuropsychological evaluation. The clinical relevance of these concerns, particularly considering the nature of concerns (e.g.

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Introduction: Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.

Methods: We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.

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Cerebrovascular disease (CVD) and Alzheimer's disease (AD) often co-occur and may impact specific cognitive domains. This study's goal was to determine effects of CVD and AD burden on cross-sectional and longitudinal executive function (EF) and memory in older adults. Longitudinally followed participants from the National Alzheimer Coordinating Center database (n = 3342) were included.

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  • In frontotemporal lobar degeneration (FTLD), abnormal protein buildup in the brain correlates with declines in social-emotional and language skills, primarily involving TDP-43 or tau proteins.
  • The study investigates how degeneration patterns in FTLD relate to gene expression of recently evolved genetic regions, using neuroimaging and transcriptomic data to examine targeted brain areas.
  • Results indicate that FTLD subtypes uniquely or overlappingly affect brain regions tied to genes evolved in humans, with a notable relationship between TDP-43 function impairment and cryptic splicing in affected genes.
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Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

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Objective: We compared the accuracy of amyloid and [F]Flortaucipir (FTP) tau positron emission tomography (PET) visual reads for distinguishing patients with mild cognitive impairment (MCI) or dementia with fluid biomarker support of Alzheimer's disease (AD).

Methods: Participants with FTP-PET, amyloid-PET, and diagnosis of dementia-AD (n = 102), MCI-AD (n = 41), non-AD diseases (n = 76), and controls (n = 20) were included. AD status was determined independent of PET by cerebrospinal fluid or plasma biomarkers.

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Mutations in progranulin ( ) cause frontotemporal dementia ( -FTD) due to deficiency of the pleiotropic protein progranulin. -FTD exhibits diverse pathologies including lysosome dysfunction, lipofuscinosis, microgliosis, and neuroinflammation. Yet, how progranulin loss causes disease remains unresolved.

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  • About 5% of Alzheimer’s patients show symptoms before they turn 65, which is called early-onset Alzheimer's disease.
  • There are two types: sporadic (happens by chance) and dominantly inherited (passed down from family).
  • This study looked at brain changes in both types and included tests on 134 sporadic cases, 89 inherited cases, and 102 people without Alzheimer’s to compare how they were affected.
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  • The rise of autoimmune diseases calls for new therapies, but there's a lack of long-term evaluation methods for these treatments.
  • Researchers used advanced techniques to analyze the unique patterns of autoantibodies in individuals, identifying stable "autoreactomes" that serve as immunological fingerprints.
  • Their findings suggest that therapies targeting B cell maturation antigen (BCMA) can significantly change these autoreactomes, implying that BCMA-based treatments might be effective for difficult-to-treat autoimmune conditions.
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While animal models of Alzheimer's disease (AD) have shown altered gamma oscillations (∼40 Hz) in local neural circuits, the low signal-to-noise ratio of gamma in the resting human brain precludes its quantification via conventional spectral estimates. Phase-amplitude coupling (PAC) indicating the dynamic integration between the gamma amplitude and the phase of low-frequency (4-12 Hz) oscillations is a useful alternative to capture local gamma activity. In addition, PAC is also an index of neuronal excitability as the phase of low-frequency oscillations that modulate gamma amplitude, effectively regulates the excitability of local neuronal firing.

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