Changes in brain structure in remitted bipolar patients
Macoveanu et al reported in the Journal of Affective Disorders (2023) that compared to controls that remitted bipolar patients had “a decline in total white matter volume over time and they had a larger amygdala volume, both at baseline and at follow-up time. Patients further showed lower cognitive performance at both times of investigation with no significant change over time….Cognitive impairment and amygdala enlargement may represent stable markers of BD early in the course of illness, whereas subtle white matter decline may result from illness progression.”
Preventing Cognitive Decline in Bipolar Disorder
Here are some suggestions from BNN Editor-in-Chief Robert M. Post, MD for preventing cognitive decline in patients with bipolar disorder.
1. Prevent Episodes with Long-term Prophylaxis
2. Remove Sedating or Impairing Drugs
3. Add Folate to Decrease Homocysteine
4. Treat Depression to Remission
5. Consider Adding:
a. Bupropion (Wellbutrin) for Mood and ADHD
b. Modafinil (Provigil) for Attention and ADHD
c. A Stimulant for ADHD
6. Add Lithium at 150mg/day for Neuroprotection in Mild Cognitive Impairment
7. Add Levitiracetam at 125mg/day to Decrease Hippocampal Hyperactivity
8. Treat Dementia Symptoms Early with:
a. Memantine (Namenda) AND/OR
b. Acetylcholine Esterase Inhibitors Such As Donepezil (Aricept)
9. Consider Adding an Anti-inflammatory Agent
Adolescent Obesity Connected to Brain Impairment
As childhood obesity has increased over the past several decades, the metabolic syndrome has also become more prevalent among children and adolescents. The metabolic syndrome consists of five measures related to obesity: elevations in fasting glucose levels or insulin resistance, a high proportion of LDL (“bad” cholesterol) to HDL (“good” cholesterol), elevated triglycerides, hypertension, and abdominal obesity or high waist circumference. A patient with three of these abnormalities would be diagnosed with the metabolic syndrome.
In adults, the metabolic syndrome has been associated with neurocognitive impairments. Researchers decided to look at adolescents with the metabolic syndrome to determine whether these brain effects are a result of long-term metabolic impairment or whether they can take place after short-term periods of poor metabolism as well. In a study published by Yau et al. in the journal Pediatrics last year, 49 adolescents with the metabolic syndrome were compared to 62 adolescents without the syndrome who had been matched for similar age, socioeconomic status, school grade, gender, and ethnicity.
The adolescents with the metabolic syndrome had lower scores on tests of math, spelling, attention, and mental flexibility, as well as a trend for lower overall intelligence. In brain measures such as hippocampal volume, amount of brain cerebrospinal fluid, and microstructural integrity in white matter tracts, the seriousness of the metabolic syndrome correlated with the level of abnormality on these measures.
Editor’s Note: It seems as though even short-term problems with metabolism can lead to brain impairments like lower cognitive performance and decreased integrity of brain structures. These effects are even seen before vascular disease and type 2 diabetes are manifest.
It is doubly important, in terms of both cardiovascular and neurobiological risks, to look out for one’s medical and psychiatric health. Reducing the abnormal components of the metabolic syndrome should produce benefits for both the cardiovascular system and the central nervous system.
Almost 40% of patients with bipolar illness in the US have the metabolic syndrome, so considerable effort will be required to improve this public health crisis.
Low Doses of Levetiracetam Acutely Improve Mild Cognitive Impairment
Levetiracetam, an anticonvulsant often used to prevent seizures in epilepsy, may improve memory by decreasing hippocampal hyperactivity. Hippocampal hyperactivity in amnestic mild cognitive impairment (aMCI) was once thought to be beneficial, but results from a recent study suggest that increased activity in this structure may contribute to memory impairment. Levetiracetam was effective for memory when given in much lower doses than those used to treat epilepsy.
In a study by Michela Gallagher and colleagues presented at the Alzheimer’s Association International Conference in 2011, a placebo-controlled, randomized crossover design was used to collect data from 17 aMCI patients and a similar number of healthy controls. Both groups went through two distinct treatment periods. People in the control group received placebos in both periods, while patients with aMCI received placebo during one period and low-dose levetiracetam (125mg twice daily) in the other period. After 2 weeks of taking the drug, hippocampal hyperactivity among aMCI patients decreased into the normal range, and memory was improved to the level of the healthy controls.
Editor’s Note: The findings from this small study are preliminary and need to be replicated in larger and longer studies before they are applied clinically. As we noted Friday, very low doses of lithium (150mg/day) prevented the progression of mild cognitive impairment compared to placebo in a one-year study. Whether these effects of levetiracetam or lithium are reliable, are of large effect, and occur by similar or different mechanisms remains to be determined.
A Daily Small Dose Of Lithium May Prevent Progression of Mild Cognitive Impairment
A very small dose of lithium, 150 mg/day, has been reported to lessen the progression of mild cognitive impairment over a period of one year compared to placebo. In a 2011 article by Orestes Forlenza and colleagues published in the British Journal of Psychiatry, the researchers reported the findings from their prospective randomized study of lithium versus placebo in 45 patients.
Editor’s Note: While these findings must still be replicated, there are several reasons to suggest that they may be reliable and valid. Read more