Why Have the Benefits of DHA Not Been Borne Out in the Treatment and Prevention of Alzheimer’s Disease? A Narrative Review Focused on DHA Metabolism and Adipose Tissue

Docosahexaenoic acid (DHA), an omega-3 fatty acid rich in seafood, is linked to Alzheimer’s Disease via strong epidemiological and pre-clinical evidence, yet fish oil or other DHA supplementation has not consistently shown benefit to the prevention or treatment of Alzheimer’s Disease. Furthermore, autopsy studies of Alzheimer’s Disease brain show variable DHA status, demonstrating that the relationship between DHA and neurodegeneration is complex and not fully understood. Recently, it has been suggested that the forms of DHA in the diet and plasma have specific metabolic fates that may affect brain uptake; however, the effect of DHA form on brain uptake is less pronounced in studies of longer duration. One major confounder of studies relating dietary DHA and Alzheimer’s Disease may be that adipose tissue acts as a long-term depot of DHA for the brain, but this is poorly understood in the context of neurodegeneration. Future work is required to develop biomarkers of brain DHA and better understand DHA-based therapies in the setting of altered brain DHA uptake to help determine whether brain DHA should remain an important target in the prevention of Alzheimer’s Disease.

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On the relationship between knowledge and memory for pictures: Evidence from the study of patients with semantic dementia and Alzheimer's disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617797005341 ◽

1997 ◽

Vol 3 (6) ◽

pp. 534-544 ◽

Cited By ~ 39

Author(s):

KIM S. GRAHAM ◽

JAMES T. BECKER ◽

JOHN R. HODGES

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Semantic Dementia ◽

Long Term Memory ◽

New Learning ◽

The Relationship ◽

Hippocampal Complex ◽

Temporal Neocortex

Current views of long-term memory presume that both the hippocampal complex and the neocortex play interactive, but separate, roles in the storage of memories. While the neocortex is considered the eventual and permanent store for our memories, the encoding of recently experienced events is thought to be initially dependent upon the hippocampus and closely related structures. Neuropsychological studies have demonstrated that damage to the medial temporal lobe results in a retrograde amnesia extending back in time, with better preservation of older memories. The converse pattern has been shown in patients with semantic dementia, who have focal atrophy of the inferolateral temporal neocortex, but relative sparing of the hippocampal complex (Graham & Hodges, 1997). Here we demonstrate that such patients can show relatively preserved new learning on a forced-choice recognition memory test (based on real and chimeric animals), while patients in the early amnestic phase of Alzheimer's disease show severely impaired learning on the same test. This result provides support for the view that new learning is primarily dependent upon the hippocampus and related structures. (JINS, 1997, 3, 534–544.)

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