Low Vitamin D and risk of delirium

Posted on November 25, 2024 by Maurice Preter MD

Low Vitamin D and risk of delirium

Title: Vitamin D levels and risk of delirium: A mendelian randomization study in the UK Biobank

Published in: Neurology, 2019

## Objective

– To estimate the effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models

## Methods

– Study design: Longitudinal analysis using the UK Biobank cohort
– Participants: 313,121 community-based volunteers of European descent aged 60+ years
– Follow-up period: Up to 9.9 years (mean 4.6 years)
– Outcome: Incident hospital-diagnosed delirium (ICD-10 F05)
– Genetic variants used:
– 6 single-nucleotide polymorphisms (SNPs) associated with vitamin D levels
– APOE variants
– Analysis: Cox competing models accounting for mortality

## Key Findings

1. Incident delirium cases:
– 544 participants were hospitalized with delirium during follow-up
– Mean age at delirium diagnosis: 71.6 years (SD 4.12 years)

2. Vitamin D genetic associations:
– Vitamin D-increasing alleles were associated with decreased risk of delirium
– Hazard ratio (HR) = 0.74 per 10 nmol/L increase in genetically instrumented vitamin D (95% CI 0.62-0.87, p=0.0004)
– No evidence for pleiotropy (MR-Egger p>0.05)

3. APOE associations:
– Participants with ≥1 APOE ε4 allele were more likely to develop delirium
– APOE ε4ε4 homozygotes: HR = 3.73 (95% CI 2.68-5.21, p=8.0 × 10^-15) compared to ε3ε3
– No interaction between APOE status and vitamin D variants

4. Sensitivity analyses:
– Results remained consistent after adjusting for time spent outdoors, excluding related participants, and adjusting for calcium genetic risk score
– Excluding prevalent dementia cases did not affect the associations

## Conclusions

– Genetic evidence supports a causal role for vitamin D levels in incident delirium
– The study suggests that trials of vitamin D supplementation for delirium prevention may be warranted

## Limitations

– Study limited to participants of European descent
– Delirium diagnoses based on hospital discharge data, potentially missing milder cases
– Unable to account for potential environmental confounders

## Implications

– Findings suggest that maintaining adequate vitamin D levels may help reduce the risk of delirium in older adults
– Further research needed to determine optimal vitamin D levels for delirium prevention

Citations:
[1] https://ppl-ai-file-upload.s3.amazonaws.com/web/direct-files/27176464/d014149f-dad3-43af-aa71-c61a27d034c3/NEUROLOGY2018905778.pdf

Posted in Aging, dietary, epigenetics, Health, keto, News, Psychiatry/Neurology | Tagged , , , , |

LED strobe lights to potentially treat Alzheimer’s disease by clearing amyloid plaques in the brain.

Posted on November 25, 2024 by Maurice Preter MD

Recent research has shown promising results in using LED strobe lights to potentially treat Alzheimer’s disease by clearing amyloid plaques in the brain. Here’s a summary of the key findings:

## The Discovery

In 2016, researchers at MIT led by Dr. Li-Huei Tsai found that exposing mice to LED lights flickering at 40 hertz (40 times per second) could significantly reduce beta amyloid plaques in the visual cortex[1]. This frequency induces gamma oscillations in the brain, which are associated with cognitive functions and appear to be impaired in Alzheimer’s disease.

## How It Works

The 40 Hz light stimulation appears to work through two main mechanisms:

1. **Reducing beta amyloid production**: The gamma oscillations induced by the light seem to suppress the production of beta amyloid proteins[1].

2. **Enhancing plaque clearance**: The treatment activates microglia, the brain’s immune cells, making them more effective at clearing out amyloid plaques[1][2].

## Expanded Research

Subsequent studies have shown that:

– Combining light and sound stimulation at 40 Hz can extend the effects to other brain regions, including the hippocampus, which is crucial for memory[2].
– Prolonged treatment (3-6 weeks) not only cleared plaques but also prevented neuron death and preserved synapses[2].
– The treatment may work by stimulating the brain’s “glymphatic system,” which helps clear metabolic waste[5].

## Human Trials

While most research has been conducted on mice, early-stage human trials have begun:

– Initial studies have confirmed the safety of the approach in humans[5].
– A large biomarker study called HOPE is currently underway, with results expected by 2025[5].

## Challenges and Controversies

It’s important to note that not all attempts to replicate the original findings have been successful. Some researchers have reported only small effects or no significant changes in amyloid levels or plaque formation[4]. This highlights the need for further research and larger-scale human trials.

## Potential as a Treatment

If proven effective in humans, this non-invasive treatment could represent a significant breakthrough in Alzheimer’s therapy:

– It’s non-invasive and potentially affordable[5].
– The treatment uses a very low intensity, ambient soft light that is barely perceptible[3].
– It could potentially be administered through special goggles or light-emitting devices that patients could use at home[3].

While these findings are exciting, it’s crucial to await the results of ongoing human trials before drawing definitive conclusions about the effectiveness of this approach in treating Alzheimer’s disease in humans.

Citations:
[1] https://news.mit.edu/2016/visual-stimulation-treatment-alzheimer-1207
[2] https://neuro.gatech.edu/simulated-brain-waves-offer-possible-treatment-alzheimers-disease
[3] https://www.bbc.com/news/health-38220670
[4] https://www.alzforum.org/news/research-news/does-flashing-light-really-lower-cortical-amyloid
[5] https://www.forbes.com/sites/williamhaseltine/2024/02/29/light-and-sound-may-help-treat-alzheimers-disease-heres-how/

 

See also: https://psychiatryneurology.net/2020/10/25/led-strobe-lights-clear-alzheimer-plaques/

Posted in keto, News, Psychiatry/Neurology | Tagged , , |

Antiseizure medication (ASM) withdrawal in seizure-free patients

Posted on November 25, 2024 by Maurice Preter MD

Here’s a very detailed summary of the practice advisory update on antiseizure medication (ASM) withdrawal in seizure-free patients:

Objective and Methods

  • Update the 1996 American Academy of Neurology practice parameter
  • Systematic review of literature published from January 1991 to March 2020

Key Findings

Adults

  • Long-term (24-60 months) risk of seizure recurrence:
    • Possibly higher among those who taper ASMs vs. those who don’t
    • 15% vs. 7% recurrence rate (Class I study)
    • Hazard ratio for recurrence: 2.9 (95% CI 1.8-4.6) in one Class III study

Children

  • No significant difference in seizure recurrence between:
    • Tapering ASMs after 2 years vs. 4 years of seizure freedom
    • Tapering at 18 months vs. 24 months (insufficient evidence)

Risk Factors for Seizure Recurrence

  • Adults:
    • Shorter seizure-free period (2 years vs. longer)
    • Abnormal psychiatric examination
    • Specific ASMs (valproate, phenobarbitone, primidone, phenytoin)
  • Children:
    • Epileptiform activity on EEG possibly increases risk

Status Epilepticus

  • ASM withdrawal possibly does not increase risk in adults

Quality of Life

  • ASM weaning possibly does not change quality of life in seizure-free adults

Mortality

  • Insufficient evidence to support or refute changes in mortality risk

Speed of ASM Withdrawal (Children)

  • No significant difference in recurrence risk between:
    • 25% reduction every 10 days to 2 weeks
    • 25% reduction every 2 months

Recommendations

  1. Clinicians should inform adults who have been seizure-free for 24 months or more that:
    • There is a possibility of increased seizure recurrence risk with ASM withdrawal
    • Recurrence risk is likely low overall but may double compared to those who continue ASMs
    • There is uncertainty about the exact risk increase
  2. Clinicians should advise children who have been seizure-free for at least 2 years that:
    • There is probably no additional risk reduction by waiting 4 years vs. 2 years to withdraw ASMs
  3. Clinicians should counsel children and caregivers that:
    • An epileptiform EEG abnormality may be associated with increased seizure recurrence risk
  4. Clinicians may advise patients that:
    • ASM withdrawal possibly does not increase the risk of status epilepticus (adults)
    • ASM withdrawal possibly does not change quality of life (adults)
  5. When withdrawing ASMs in children, clinicians may consider:
    • Using a withdrawal rate of 25% reduction every 10 days to 2 weeks
    • Or using a withdrawal rate of 25% reduction every 2 months

Limitations and Considerations

  • Limited high-quality evidence for many aspects of ASM withdrawal
  • Individualized decision-making is crucial, considering patient preferences and risk factors
  • Further research needed on specific electroclinical syndromes and post-epilepsy surgery patients
  • EEG type and duration for assessing recurrence risk not specified in studies

This summary provides a comprehensive overview of the key points from the practice advisory update on ASM withdrawal in seizure-free patients.

Source: Gloss et al. 2021

Posted in Psychiatry/Neurology | Tagged , |

Lyme disease in neurology – a primer

Posted on November 25, 2024 by Maurice Preter MD

Here is a detailed summary of the key points about Lyme disease and its neurologic complications:

Causative agent and transmission:

  • Caused by spirochetes of the genus Borrelia, primarily Borrelia burgdorferi in North America
  • Transmitted by bite of infected Ixodes tick
  • Tick must typically remain attached for 24-48 hours to transmit Borrelia

• Geographic distribution:

  • Highest incidence in northeastern and north-central United States
  • Endemic areas include Connecticut, Vermont, Maine, Massachusetts, New Hampshire, Rhode Island, New Jersey, Pennsylvania, New York, Wisconsin, Minnesota

• Clinical manifestations:

  • Initial sign is often erythema migrans rash at site of tick bite
  • Can progress to systemic involvement if untreated
  • Most common neurologic complications:
    1. Cranial neuritis (especially facial nerve palsy)
    2. Meningitis
    3. Radiculoneuritis/mononeuropathy multiplex

• Diagnosis:

  • Two-step serologic testing recommended by CDC:
    1. Enzyme-linked immunosorbent assay (ELISA)
    2. If ELISA positive/borderline, Western blot for IgM and IgG
  • CSF analysis may be needed in early infection or equivocal cases
  • CSF typically shows lymphocytic pleocytosis in active neuroborreliosis

• Treatment:

  • Oral doxycycline for most cases of neuroborreliosis
  • IV antibiotics (ceftriaxone, cefotaxime, penicillin G) for severe manifestations
  • Duration typically 2-4 weeks

• Post-treatment Lyme disease syndrome:

  • Persistent symptoms like fatigue, pain, cognitive issues after treatment
  • Not indicative of ongoing infection
  • No benefit from prolonged antibiotic therapy

• Chronic Lyme disease controversy:

  • Not a recognized clinical entity
  • Symptoms attributed to Lyme without evidence of infection
  • Long-term antibiotics not recommended

• Key points for neurologists:

  • Consider Lyme in endemic areas for patients with facial palsy, meningitis, radiculitis
  • Understand proper diagnostic testing and interpretation
  • Recognize limitations of serology in early infection
  • Be aware of guidelines for appropriate antibiotic treatment
Posted in News |

Essential tremor is a complex neurological disorder characterized by rhythmic shaking, primarily affecting the hands, head, and voice.

Posted on November 25, 2024 by Maurice Preter MD

Essential tremor is a complex neurological disorder characterized by rhythmic shaking, primarily affecting the hands, head, and voice. Here’s a comprehensive overview of its diagnosis and management:

Clinical Manifestations

Limb Tremor

Essential tremor primarily manifests as a bilateral upper extremity action tremor. Key features include:

  • Kinetic tremor with or without postural tremor
  • Frequency between 8-12 Hz
  • Kinetic tremor more severe than postural tremor in about 95% of cases
  • Mild to moderate asymmetry common
  • Rest tremor possible in longstanding cases (prevalence 2-46%)
  • Intention tremor may develop later, associated with disease duration

Head Tremor

Head tremor is a common late manifestation:

  • Present in about 39% of patients
  • More common in women and older patients
  • Often exacerbated during phonation tasks
  • May have an intention component
  • Can be “no-no” (horizontal), “yes-yes” (vertical), or mixed directional

Vocal Tremor

Vocal changes are frequent, especially in older patients:

  • More common in women
  • Patients describe voice as “weak,” “unstable,” “shaky,” or “hoarse”
  • Can involve muscles of the palate, pharynx, tongue, and larynx

Other Manifestations

  • Chin/jaw tremor: Uncommon, increases with disease severity
  • Balance difficulties and gait impairment
  • Hearing loss: Higher prevalence of hearing impairment and hearing aid use
  • Olfactory changes: Mixed findings, may be normal in many cases
  • Eye findings: Oculomotor changes, including square wave jerks and altered saccades

Psychiatric and Cognitive Symptoms

  • Higher rates of depression, anxiety, and sleep disturbances
  • Increased pain severity and interference
  • Mild cognitive impairment, particularly in executive function, attention, and working memory

Diagnosis

Essential tremor is primarily a clinical diagnosis based on history and examination:

  • Assess tremor during different activities and impact on daily living
  • Family history and alcohol responsiveness can be helpful clues
  • Perform multiple bedside tests (e.g., arm extension, finger-to-nose movements, spiral drawing)
  • Complete neurological examination to rule out other conditions

Diagnostic pearls:

  • Extension-flexion at the wrist during arm extension
  • Intention tremor in finger-to-nose testing (>25% of cases)
  • Characteristic axis in writing and spiral drawings (8-2 o’clock for right-handed, 10-4 o’clock for left-handed)
  • “Head snap” during finger-to-nose examination in up to 20% of cases

Classification

The International Parkinson and Movement Disorder Society redefined essential tremor in 2018 as a syndrome, recognizing its heterogeneity. The new classification includes:

  • Essential tremor
  • Essential tremor plus (with additional neurological signs)

Treatment

First-line treatments:

  • Propranolol
  • Primidone

For severe cases:

  • Deep brain stimulation (traditional target: ventral intermediate nucleus of thalamus; emerging target: caudal zona incerta)
  • MRI-guided high-intensity focused ultrasound

Emerging treatments:

  • Novel oral medications
  • Chemodenervation
  • Noninvasive neuromodulation

Prognosis

Essential tremor is progressive, but less than 10% of patients with long disease duration develop significant disability. Predictors of faster progression include:

  • Longer disease duration
  • Asymmetrical tremor
  • Isolated limb involvement at onset
  • Older age of onset

In conclusion, essential tremor is a complex and heterogeneous disorder requiring careful clinical assessment for accurate diagnosis and appropriate management.

 
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