Majid Fotuhi

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (13)93.21 Total impact

  • Majid Fotuhi, David Do, Clifford Jack
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    ABSTRACT: The hippocampus is particularly vulnerable to the neurotoxic effects of obesity, diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea, bipolar disorder, clinical depression and head trauma. Patients with these conditions often have smaller hippocampi and experience a greater degree of cognitive decline than individuals without these comorbidities. Moreover, hippocampal atrophy is an established indicator for conversion from the normal ageing process to developing mild cognitive impairment and dementia. As such, an important aim is to ascertain which modifiable factors can have a positive effect on the size of the hippocampus throughout life. Observational studies and preliminary clinical trials have raised the possibility that physical exercise, cognitive stimulation and treatment of general medical conditions can reverse age-related atrophy in the hippocampus, or even expand its size. An emerging concept--the dynamic polygon hypothesis--suggests that treatment of modifiable risk factors can increase the volume or prevent atrophy of the hippocampus. According to this hypothesis, a multidisciplinary approach, which involves strategies to both reduce neurotoxicity and increase neurogenesis, is likely to be successful in delaying the onset of cognitive impairment with ageing. Further research on the constellation of interventions that could be most effective is needed before recommendations can be made for implementing preventive and therapeutic strategies.
    Nature Reviews Neurology 03/2012; 8(4):189-202. · 15.52 Impact Factor
  • Majid Fotuhi, David Do
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2010; 6(4).
  • Neurology 11/2009; 73(19):1607; author reply 1607-8. · 8.30 Impact Factor
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    ABSTRACT: Individuals over 80 years of age represent the most rapidly growing segment of the population, and late-life dementia has become a major public health concern worldwide. Development of effective preventive and treatment strategies for late-life dementia relies on a deep understanding of all the processes involved. In the centuries since the Greek philosopher Pythagoras described the inevitable loss of higher cognitive functions with advanced age, various theories regarding the potential culprits have dominated the field, ranging from demonic possession, through 'hardening of blood vessels', to Alzheimer disease (AD). Recent studies suggest that atrophy in the cortex and hippocampus-now considered to be the best determinant of cognitive decline with aging-results from a combination of AD pathology, inflammation, Lewy bodies, and vascular lesions. A specific constellation of genetic and environmental factors (including apolipoprotein E genotype, obesity, diabetes, hypertension, head trauma, systemic illnesses, and obstructive sleep apnea) contributes to late-life brain atrophy and dementia in each individual. Only a small percentage of people beyond the age of 80 years have 'pure AD' or 'pure vascular dementia'. These concepts, formulated as the dynamic polygon hypothesis, have major implications for clinical trials, as any given drug might not be ideal for all elderly people with dementia.
    Nature Reviews Neurology 11/2009; 5(12):649-58. · 15.52 Impact Factor
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    ABSTRACT: Long-chain omega-3 fatty acids could have neuroprotective properties against dementia, which is becoming a major global public health issue. We conducted a systematic review of the literature to establish the association between eating fish (a source of long-chain omega-3 fatty acids) or taking long-chain omega-3 fatty acid supplements and the risk of cognitive decline or Alzheimer disease (AD). We identified eleven observational studies and four clinical trials. All three observational studies that used cognitive decline as an outcome reported significant benefits, whereas only four of eight observational studies that used incidence of AD or dementia as an outcome reported positive findings. None of four small clinical trials provided convincing evidence for the use of this approach in the prevention or treatment of any form of dementia. In summary, the existing data favor a role for long-chain omega-3 fatty acids in slowing cognitive decline in elderly individuals without dementia, but not for the prevention or treatment of dementia (including AD). This apparent dichotomy might reflect differences in study designs with regard to participants, dosages, the ratio of long-chain omega-3 to omega-6 fatty acids, or the choice of outcome measurements. Large clinical trials of extended duration should help to provide definitive answers.
    Nature Clinical Practice Neurology 04/2009; 5(3):140-52. · 7.64 Impact Factor
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    ABSTRACT: Vestibular migraine (VM), also known as migraine-associated vertigo, is a common cause of dizziness in adults. We performed a comprehensive literature search regarding treatment for VM or migraine-associated vertigo during the period of 1990-2008 and used, individually or in combination, the search terms VM, migraine-associated vertigo, migraine-associated dizziness, migrainous vertigo, migraine and vertigo, migraine and disequilibrium, and headache and vertigo. We found nine publications that address treatment strategies for VM. One small randomized clinical trial found some benefit from the use of zolmitriptan for abortive treatment of VM. The other eight observational studies showed marginal improvement with migraine prophylactic medications such as nortriptyline, verapamil, or metoprolol. Until more specific treatment options become available, patients with VM need to be managed with similar prophylactic and abortive strategies as those used for migraine in adults.
    Journal of Neurology 04/2009; 256(5):711-6. · 3.58 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2009; 5(4).
  • Majid Fotuhi, Payam Mohassel
    Alzheimer's and Dementia 07/2008; 4(4). · 17.47 Impact Factor
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    ABSTRACT: Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or nonsteroidal anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State examination up to three times during a period of 8 years. Those who used a combination of vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than nonusers (P < .05). This apparent effect was attributable entirely to participants with the APOE epsilon4 allele, whose users declined by 2.25 fewer points than nonusers every 3 years (P < .05). These results suggest that among elderly individuals with an APOE epsilon4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2008; 4(3):223-7. · 14.48 Impact Factor
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    ABSTRACT: Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time. Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling. Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02). Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE epsilon4 alleles.
    Neurology 08/2007; 69(3):275-82. · 8.30 Impact Factor
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    ABSTRACT: We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly.
    The Journal of Nutrition Health and Aging 01/2007; 11(3):230-7. · 2.39 Impact Factor
  • Article: P4-375
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2005; 1(1).

Publication Stats

376 Citations
93.21 Total Impact Points

Institutions

  • 2008–2012
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, Maryland, United States
  • 2009
    • LifeBridge Health
      Baltimore, Maryland, United States