Dementia: If you have the gene for Dementia, now what?

For my dear friends with parents with Alzheimer's:

There is a great deal of research trying to understand why certain people develop dementia and Alzheimers and others do not. 

A relatively recent paper shows diet plays a big part. The paper below show the combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

I wonder if this is helpful for glaucoma also?

More research needed.

SLC

1. 

Journal of Alzheimer’s Disease 54 (2016) 297–306

DOI 10.3233/JAD-160329

IOS Press

297

Multi-Vitamin B Supplementation

Reverses Hypoxia-Induced Tau

Hyperphosphorylation and Improves

Memory Function in Adult Mice

Lixia Yu1, Yuan Chen1, Weiguang Wang, Zhonghai Xiao and Yan Hong∗

Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China

Accepted 4 June 2016

Abstract. Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and

increase the risk of dementia including Alzheimer’s disease (AD). The present study was undertaken in order to examine

whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and

AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic

model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC).

Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and

step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3 phosphorylation were detected

by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group

exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262,

Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly,

the levels of Ser9-phosphorylated GSK-3 were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

#2.

Keywords: Homocysteine, hypoxia, memory improvement, tau phosphorylation, vitamin B

Detailed neuropsychological testing is not recommended on the basis of APOE allele status, but may be considered for obtaining more information about the presence, character, and extent of cognitive impairment when these measures are not adequately ascertained by clinical examination. Although the genetic test result for this patient included language to suggest that Alzheimer disease was a cause of or contributor to the patient's cognitive symptoms, the unremarkable neuropsychological testing (within expected range based on age and education), neurologic examination, and brain magnetic resonance imaging do not support a diagnosis of dementia or Alzheimer disease. The presence of a single first-degree relative with Alzheimer disease dementia is associated with increased risk (relative risk, 1.73) that is weaker than the risk conferred by APOE ɛ4.⁶ Additional diagnostic testing is not warranted, and APOE ɛ4 status would not change clinical care.

The neuropathological features of Alzheimer disease include amyloid plaques and hyperphosphorylated tau in the brain parenchyma. CSF biomarkers (low CSF amyloid and high CSF phosphorylated tau) can identify Alzheimer disease pathophysiologic changes in the central nervous system, but negative results from this invasive test do not rule out Alzheimer disease dementia in the future. Although not directly indicative of amyloid and tau pathology, FDG-PET can differentiate Alzheimer disease from frontotemporal dementia based on its distinctive pattern of decreased temporoparietal glucose uptake, which can precede visualized atrophy in these regions on magnetic resonance imaging. FDG-PET was unnecessary for this patient because of the lack of clinical features of either cause of dementia. Patient education on APOE ɛ4 can be accomplished in a primary care setting or in a neurology clinic and does not necessarily require formal genetic counseling.

Alternative Diagnostic Approaches

Amyloid PET imaging consists of noninvasive detection of elevated amyloid in the brain and may be useful in patients with cognitive impairment of uncertain etiology and when a molecular diagnosis of Alzheimer disease would alter management.⁷ However, greater than 70% of individuals older than age 65 who have a positive amyloid PET scan and normal cognition never develop dementia in their lifetime,⁸ limiting the utility of amyloid PET in people with normal cognitive function. Blood-based assays for amyloid and tau have shown promise in the research setting.⁹

Patient Outcome

The patient was counseled on the relationship between APOE ɛ4 and Alzheimer disease and provided with information about lifestyle interventions to help maintain cognition (via cognitive and social engagement, physical exercise, healthy diet, quality sleep, and control of cerebrovascular disease risk factors), and scheduled for follow-up.¹⁰ Two years following the identification of the positive APOE ɛ4 test result, the patient continues to have subjective memory and word-finding concerns but has not demonstrated cognitive decline on repeat neuropsychological testing.

Clinical Bottom Line

• The apolipoprotein E (APOE) ɛ4 allele is associated with increased risk of Alzheimer disease in a dose-dependent pattern.

• APOE ɛ4 is neither necessary nor sufficient for Alzheimer disease, cannot rule in or rule out the development of Alzheimer disease dementia, and is not currently recommended in the clinical evaluation of cognitive impairment.