Brain Atrophy: Causes and Inhibitors of Brain Shrinkage

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Brain atrophy, or brain shrinkage, is the opposite of neurogenesis. Brain atrophy describes a loss of neurons and the connections between them.

Brain atrophy can be categorized as either general or focal. With general brain atrophy, all of the brain shrinks. With focal brain atrophy, shrinkage of the brain affects a limited area of the brain which often results in decreased functions in the area that area controls. For example, if the cerebrum atrophizes, then conscious thought and voluntary processes may be impaired.

Even if you do not have a chronic disease, you may be losing as much as 0.4% of your brain mass every year. [1] The rate of brain shrinkage increases with age and is a major factor in early cognitive decline and premature death. [2] Age related cognitive decline occurs in tandem with the physical degradation of brain structure. [3]

By the age of 60, approximately .5 to 1% of brain volume is lost per year. By the time you reach age 75, your brain is on average of 15% smaller than it was when you were in your mid-20’s.

Even though brain shrinkage is progressive, a growing number of neuroscientists believe that brain shrinkage can be slowed or even reversed. [4]

Medical science has recognized a number of conditions and behaviors that cause brain atrophy.

Table: Common Causes of Brain Atrophy

Brain Atrophy Causes
Anatomy/Condition Effect Notes
Homocysteine
Homocysteine is a risk factor for brain atrophy. Supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment. [5]
Sleep
Poor sleep quality was associated with reduced volume within the right superior frontal cortex in cross-sectional analyses, and an increased rate of atrophy within widespread frontal, temporal, and parietal regions in longitudinal analyses. [6]
Hypertension
Studies have shown that both high and low blood pressure (BP) may play a role in the etiology of brain atrophy. High BP in midlife has been associated with more brain atrophy later in life. [7]
Hypoperfusion
Normal aging is associated with diminished blood flow to the brain. This pathology is known as hypoperfusion and causes cell injury and death. The combination of hypertension and hypoperfusion is associated with smaller brain volume. [8]
Type 2 Diabetes
New research has shown that cognitive decline in people with type 2 diabetes is likely due to brain atrophy, or shrinkage, that resembles patterns seen in the early stages of Alzheimer’s disease. [9]
Obesity
Higher body mass index (BMI, a measure of obesity) is associated with lower brain volume in obese and overweight people. [10]
Smoking
Any lifetime history of smoking (even if you currently do not smoke) is associated with faster brain shrinkage in multiple brain regions, compared with people who never smoked. [11]
Alcohol
Heavy drinkers are 80% more likely than nondrinkers to sustain frontal lobe shrinkage, compared with nondrinkers,49 and 32% more likely to have enlargement of the ventricles, indicating shrinkage from within. [12]

Table below lists the substances that have been studied for their ability to inhibit or prevent brain atrophy.

Table: Nootropics/Nutraceuticals/Foods/Herbs/Spices that Inhibit and Prevent Brain Atrophy

Brain Atrophy Nutrients
Category Nootropics/Nutraceuticals/Foods/Herbs/Spices References
Foods
Pomegranate [13]
Lipids
Docosahexaenoic acid (DHA) [14] [15]
Polyphenols
Resveratrol [16]
Vitamins
B Complex Vitamins (reduces homocysteine levels) [17]
Vitamin B12 [18]

References:

[1] Enzinger C, Fazekas F, Matthews PM, et al. Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology. 2005 May 24;64(10):1704-11.

Hedman AM. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Human Brain Mapping. 2012;33:1987-220.

[2] Hedman AM. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Human Brain Mapping. 2012;33:1987-220.

Olesen PJ, Guo X, Gustafson D, et al. A population-based study on the influence of brain atrophy on 20-year survival after age 85. Neurology. 2011 Mar 8;76(10):879-86.

Guo X, Steen B, Matousek M, et al. A population-based study on brain atrophy and motor performance in elderly women. J Gerontol A Biol Sci Med Sci. 2001 Oct;56(10):M633-7.

Henneman WJ, Sluimer JD, Cordonnier C, et al. MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population. Stroke. 2009 Feb;40(2):492-8.

Johansson L, Skoog I, Gustafson DR, et al. Midlife psychological distress associated with late-life brain atrophy and white matter lesions: a 32-year population study of women. Psychosom Med. 2012 Feb-Mar;74(2):120-5.

Olesen PJ, Gustafson DR, Simoni M, et al. Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly. Neuropsychopharmacology. 2010 Dec;35(13):2638-45.

[3] Fjell A et al. Structural brain changes in aging: courses, causes and cognitive consequences. Revs Neurosci. 2010; 21(3):182-221.

Fjell A et al. Structural brain changes in aging: courses, causes and cognitive consequences. Revs Neurosci. 2010; 21(3):182-221.

Fjell A et al. Structural brain changes in aging: courses, causes and cognitive consequences. Revs Neurosci. 2010; 21(3):182-221.

[4] Draganski B, Lutti A, Kherif F. Impact of brain aging and neurodegeneration on cognition: evidence from MRI. Curr Opin Neurol. 2013 Dec;26(6):640-5.

[5] Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

[6] Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults

[7] Blood Pressure and Progression of Brain AtrophyThe SMART-MR Study

Alosco ML, Brickman AM, Spitznagel MB, et al. Independent and interactive effects of blood pressure and cardiac function on brain volume and white matter hyperintensities in heart failure. J Am Soc Hypertens. 2013 Sep-Oct;7(5):336-43.

Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab. 2008 Jun;7(6):476-84.

Jennings JR, Mendelson DN, Muldoon MF, et al. Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure. J Hum Hypertens. 2012 May;26(5):295-305.

[8] Liu Y, Zhu X, Feinberg D, et al. Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med. 2012 Sep;68(3):912-22.

[9] Brain atrophy linked with cognitive decline in diabetes

[10] Kiliaan AJ, Arnoldussen IA, Gustafson DR. Adipokines: a link between obesity and dementia? Lancet Neurol. 2014 Sep;13(9):913-23.

Raji CA, Ho AJ, Parikshak NN, et al. Brain structure and obesity. Hum Brain Mapp. 2010 Mar;31(3):353-64.

[11] Kubota K, Matsuzawa T, Fujiwara T, et al. Age-related brain atrophy enhanced by smoking: a quantitative study with computed tomography. Tohoku J Exp Med. 1987 Dec;153(4):303-11.

Durazzo TC, Meyerhoff DJ, Nixon SJ. Chronic cigarette smoking: implications for neurocognition and brain neurobiology. Int J Environ Res Public Health. 2010 Oct;7(10):3760-91.

Durazzo TC, Insel PS, Weiner MW. Greater regional brain atrophy rate in healthy elderly subjects with a history of cigarette smoking. Alzheimers Dement. 2012 Nov;8(6):513-9.

[12] Gu Y, Scarmeas N, Short EE, et al. Alcohol intake and brain structure in a multiethnic elderly cohort. Clin Nutr. 2014 Aug;33(4):662-7.

Kubota M, Nakazaki S, Hirai S, Saeki N, Yamaura A, Kusaka T. Alcohol consumption and frontal lobe shrinkage: study of 1432 nonalcoholic subjects. J Neurol Neurosurg Psychiatry. 2001 Jul;71(1):104-6.

Mukamal KJ, Longstreth WT, Jr., Mittleman MA, Crum RM, Siscovick DS. Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study. Stroke. 2001 Sep;32(9):1939-46.

[13] Hartman RE, Shah A, Fagan AM, et al. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2006 Dec;24(3):506-15.

Kumar S, Maheshwari KK, Singh V. Protective effects of Punica granatum seeds extract against aging and scopolamine induced cognitive impairments in mice. Afr J Tradit Complement Altern Med. 2008;6(1):49-56.

Rojanathammanee L, Puig KL, Combs CK. Pomegranate polyphenols and extract inhibit nuclear factor of activated T-cell activity and microglial activation in vitro and in a transgenic mouse model of Alzheimer disease. J Nutr. 2013 May;143(5):597-605.

Choi SJ, Lee JH, Heo HJ, et al. Punica granatum protects against oxidative stress in PC12 cells and oxidative stress-induced Alzheimer’s symptoms in mice. J Med Food. 2011 Jul-Aug;14(7-8):695-701.

Bookheimer SY, Renner BA, Ekstrom A, et al. Pomegranate juice augments memory and FMRI activity in middle-aged and older adults with mild memory complaints. Evid Based Complement Alternat Med. 2013;2013:946298.

[14] Hennebelle M, Champeil-Potokar G, Lavialle M, Vancassel S, Denis I. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus. Nutr Rev. 2014 Feb;72(2):99-112.

Tatebayashi Y, Nihonmatsu-Kikuchi N, Hayashi Y, Yu X, Soma M, Ikeda K. Abnormal fatty acid composition in the frontopolar cortex of patients with affective disorders. Transl Psychiatry. 2012;2:e204.

Virtanen JK, Siscovick DS, Lemaitre RN, et al. Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the Cardiovascular Health Study. J Am Heart Assoc. 2013 Oct;2(5):e000305.

Pottala JV, Yaffe K, Robinson JG, Espeland MA, Wallace R, Harris WS. Higher RBC EPA + Docosahexaenoic acid (DHA) corresponds with larger total brain and hippocampal volumes: WHIMS-MRI study. Neurology. 2014 Feb 4;82(5):435-42.

[15] Association of fish oil supplement use with preservation of brain volume and cognitive function.

[16] Moriya J, Chen R, Yamakawa J, Sasaki K, Ishigaki Y, Takahashi T. Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells. Biol Pharm Bull. 2011;34(3):354-9.

Rege SD, Kumar S, Wilson DN, et al. Resveratrol protects the brain of obese mice from oxidative damage. Oxid Med Cell Longev. 2013;2013:419092.

Chang HC, Tai YT, Cherng YG, et al. Resveratrol attenuates high-fat diet-induced disruption of the blood-brain barrier and protects brain neurons from apoptotic insults. J Agric Food Chem. 2014 Apr 16;62(15):3466-75.

Witte AV, Kerti L, Margulies DS, Floel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014 Jun 4;34(23):7862-70.

[17] Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE [online journal]. 2010;5(9):e12244.

Erickson KI, Suever BL, Prakash RS, Colcombe SJ, McAuley E, et al. Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: A voxel-based morphometry study. Brain Res 2008;1199:20–6.

Jack CR, Jr., Shiung MM, Gunter JL, O’Brien PC, Weigand SD, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology 2004;62:591–600.

Kelland K. B vitamins found to halve aging brain shrinkage. Reuters Health, September 9, 2010.

Institute of Medicine, Food and Nutrition Board. Folate. In: Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington DC: National Academy Press; 1998, 196-305.

B vitamins slow brain atrophy in people with memory problems

[18] Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy.


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