NEURAL REGENERATION RESEARCH www.nrronline.

org

REVIEW

Dietary habits, lifestyle factors and neurodegenerative

diseases
Aurel Popa-Wagner1, *, #, Dinu Iuliu Dumitrascu2, #, Bogdan Capitanescu3, Eugen Bogdan Petcu1, Roxana Surugiu4, Wen-Hui Fang5,
Danut-Adrian Dumbrava4, *
1 Griffith University School of Medicine, Gold Coast Campus, QLD, Australia
2 Department of Anatomy, UMF “Iuliu Hatieganu”, Cluj-Napoca, Romania
3 Department of Human Anatomy, Faculty of Medicine, University of Medicine and Pharmacy, Craiova, Romania
4 Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy, Craiova, Romania
5 School of Healthcare Science, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK

Abstract *Correspondence to:

Aurel Popa-Wagner, PhD,
Worldwide stroke is increasing in parallel with modernization, changes in lifestyle, and the growing elderly aurel.popa-wagner@
population. Our review is focused on the link between diet, as part of ‘modern lifestyle’, and health in the geriatrics-healthyageing.com;
context of genetic predisposition of individuals to ‘unhealthy’ metabolic pathway activity. It is concluded Danut-Adrian Dumbrava, MD,
that lifestyle including high sugar diets, alcohol and tobacco addiction or high fat diets as well as ageing, [email protected].
brain injury, oxidative stress and neuroinflammation, negatively influence the onset, severity and duration
of neurodegenerative diseases. Fortunately, there are several healthy dietary components such as polyun- #Both authors contributed
saturated fatty acids and the anti-oxidants curcumin, resveratrol, blueberry polyphenols, sulphoraphane, equally to this work.
salvionic acid as well as caloric restriction and physical activity, which may counteract ageing and associat-
ed neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain. orcid:
0000-0003-4574-8605
Key Words: brain injury; dietary habits; lifestyle; metaflammation; neurodegeneration; oxidative stress; type 2 (Aurel Popa-Wagner)
diabetes mellitus
doi: 10.4103/1673-5374.266045

Received: December 21, 2018

Accepted: June 20, 2019

Introduction review focuses on the link between lifestyle and health in the
Worldwide stroke is increasing in parallel with moderniza- context of genetic predisposition of individuals to ‘unhealthy’
tion, changes in lifestyle, and the growing elderly population. metabolic pathway activities by performing a systematic lit-
Individuals with a healthy, low-risk lifestyle (no smoking, erature search of the last 10 years. Data were from PubMed
daily exercise, moderate alcohol consumption and having a and Google Scholar.
moderate weight during their mid-forties) had a significantly
lower risk of neurodegenerative diseases than the high-risk Mechanisms Linking Lifestyle and
lifestyle group. Therefore, the relatively high incidence of Diet-Induced Metabolic Inflammation to
neurodegenerative diseases may be due in part to the nega-
tive influence of daily risk factors including (Donnan et al.,
Cerebrovascular Diseases
2008): stress, lack of physical exercise, unhealthy nutrition, Fuelled by an increasingly sedentary lifestyle along with an
obesity, high cholesterol levels in plasma, smoking, alcohol- unhealthy, “westernised” diet, the type 2 diabetes mellitus
ism or arterial hypertension. (T2DM) epidemic has expanded in parallel with obesity in
Some intrinsic factors such as ageing, but also brain injury modern societies.
and associated exaggerated neuroinflammation, oxidative For decades, a diet rich in saturated fat and cholesterol
stress, as well as lifestyle factors including high sugar diets has been seen as the major dietary factor leading to an in-
and high fat diets, alcohol and tobacco addiction, nega- creased risk of atherosclerosis and cerebrovascular diseases
tively influence neurodegeneration. But there are many (Hu and Willett, 2002). Indeed, bad nutritional habits may
components in our diet (polyunsaturated fatty acids, the lead to metabolic disorders including hypertension, met-
antioxidants curcumin, resveratrol, blueberry polyphenols, abolic syndrome, cerebrovascular diseases, stroke, insulin
sulphoraphane and salvionic acid) as well as caloric restric- resistance and T2DM, all triggered by a systemic, chronic
tion, along with physical exercise that may allow us to live a inflammation, also called metabolic inflammation or meta-
healthier and longer life (Poulose et al., 2017). Although the flammation (Olefsky and Glass, 2010). It has been postulated
progress of neurodegenerative diseases is, to some extent, that lipid hormones including sphingolipids and eicosanoids
measurable through anthropometric, lifestyle, and clinical in concert with cytokines and adipokines play an important
factors, the mechanisms underlying neurodegenerative role in this process by inducing adverse regulatory responses
disease progression are not fully understood. The current in target cells such as macrophages. However, it has been

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 Popa-Wagner A, Dumitrascu DI, Capitanescu B, Petcu EB, Surugiu R, Fang WH, Dumbrava DA (2020) Dietary habits, lifestyle factors and
neurodegenerative diseases. Neural Regen Res 15(3):394-400. doi:10.4103/1673-5374.266045

estimated that 30% to 70% of T2DM risk can be attributed The lowest PD severity score was associated with plant and
to genetic background (Poulsen et al., 1999). Therefore, the fish-based diets. Only coenzyme Q10 and fish oil among nu-
investigation of gene-environment interactions holds prom- tritional supplements had a statistically significant correla-
ise in shedding light on the interplay between environmental tion with PD, reducing rates of PD progression. Regarding
factors and genetics (Cornelis and Hu, 2012). nutritional behaviours, patients who prepared their meals by
Genome-wide associations studies between genetic vari- themselves had a protection against PD whereas those who
ants and traits has become an essential approach in identify- bought their meals from local markets or ate out had lower
ing disease-causative genes. Genome wide single nucleotide patient-reported outcomes in PD scores (Mischley et al.,
polymorphism (SNP) typing technology applied to large 2017).
sample sets has provided insights into the pathogenesis of
T2DM (http://www.genome.gov/gwastudies/). However, the Oxidative stress, anti-oxidants and neurodegenerative
identification of these loci does not contribute to the clinical diseases
prediction of diabetes beyond that of traditional risk factors, It is known that oxidative stress plays an important role in
such as sedentary lifestyle, obesity, or family history of di- the ageing process and neurodegenerative diseases. As it is
abetes. Nevertheless, the recent identification of a genomic a powerful antioxidant, the neuroprotective properties of
SNP pattern providing insights into the mechanisms under- ascorbic acid mitigate neuroinflammation and amyloid-beta
lying obesity will enable a deeper understanding of the asso- peptide deposition by trapping free radicals and suppress-
ciation between SNPs and lifestyle factors (Locke et al., 2015; ing the expression of pro-inflammatory genes. In a recent
Shungin et al., 2015). Furthermore, genome-wide association study, Kim et al. (2015) investigated the effects of high-dose
studies are beginning to unravel the genetic contribution ascorbic acid supplementation (1250 mg/d) in humans.
to human metabolic individuality by analysing the clinical Thus, supplementation of daily food with ascorbic acid for
associations between SNPs and so-called intermediate phe- eight weeks, led to a reduction in advanced glycation end
notypes (Bictash et al., 2010; Illig et al., 2010; Teslovich et al., products, especially in non-smoking men. The reduction in-
2010; Suhre et al., 2011; Kettunen et al., 2012). glycation end products was also associated with an improve-
ment in the levels of plasma high-density lipoprotein and
Nutrition and Neurodegenerative Diseases an improvement in low-density lipoprotein composition.
Trace elements: iron Therefore, supplementation with ascorbic acid could exert
Iron status is involved in the pathophysiology of a series of protective effects against atherosclerosis and related systemic
conditions found in elderly people, both men and women. inflammation by reducing conversion of macrophages to
The correlation between low levels of haemoglobin and high foam cells. At a molecular level, this study demonstrated
levels of ferritin might be related to an increased disease pa- that ascorbic acid negatively regulates post-transcriptional
thology, even though iron status seems to be the result, not expression of several microRNAs. Thus, ascorbic acid con-
the cause, of these changes. Many studies are highlighting sumption led to a 90% decrease in miR155 levels, suggesting
iron homeostasis in mitochondria and the impact of inflam- that high doses of ascorbic acid may significantly diminish
mation on iron overload in neurodegenerative diseases. An inflammation by modulating miRNA levels (Kim et al.,
excess of redox-active iron in the mitochondrial redox-active 2015).
pool, will result in an overproduction of hydroxyl radicals An association between cognitive impairment and antiox-
and an increment in oxidative stress. Then again, lack of iron idant capacity has been suggested by many studies (Soysal et
will impede various processes which utilize iron as a cofactor al., 2017). Even though, in large population studies, the cor-
(Urrutia et al., 2014). Another study published in 2018 by relation between ascorbic acid intake and neuroprotection
Wawer and his colleagues which investigated if Parkinson’s in the onset of Alzheimer’s disease (AD) has not yet been
disease (PD) patients with sleep behaviour disorder have demonstrated, a synergic association between ascorbic acid
different patterns of neurodegeneration when compared to and vitamin E supplementation was shown to have a preven-
patients without sleep behaviour disorder, suggests that there tive action on AD (Monacelli et al., 2017).
is a positive association between unified PD rating scale A study conducted in 2016 used a mouse AD model
(UPDRS III) score and iron levels and between iron levels (APPswe/PS1dE9 double transgenic mice) in order to ob-
and inflammatory markers (Wawer et al., 2018). serve the anti-oxidative effects of curcuma at the level of
synapse-associated proteins. The treatment was adminis-
Long chain polyunsaturated fatty acids tered for 6 months, the results showing an amelioration of
Regarding the influence of diet and lifestyle variables on PD the quantity and ultrastructure of synapses. The expression
severity, Mischley and her colleagues conducted a study, of PSD95 and Shank1 was decreased in the hippocampus
which aimed to describe how modifiable lifestyle factors CA1 area of the transgenic mice shown by western blot assay
can influence the rate of progression of PD. They included and immunohistochemistry techniques, as compared to the
in the study with 1053 participants, who had a diagnosis of treatment group, which showed an increased expression of
idiopathic PD. To assess PD severity, an assessment tool was the proteins. This finding indicated that curcuma consump-
used for patient-reported outcomes in PD. To quantify di- tion could improve the function and structure of synapses
etary intake, a food frequency questionnaire was developed. through the regulation of PSD95 and Shank1 proteins (Feng

395
Popa-Wagner A, Dumitrascu DI, Capitanescu B, Petcu EB, Surugiu R, Fang WH, Dumbrava DA (2020) Dietary habits, lifestyle factors and
neurodegenerative diseases. Neural Regen Res 15(3):394-400. doi:10.4103/1673-5374.266045

et al., 2016). Another study using the same AD mouse mod- lipids, fasting glucose and transaminases. A direct inverse
el focuses on the mechanism involved in impaired insulin correlation was found between PD duration and body fat
signaling and insulin resistance. The immunohistochemistry percentage, as well as body mass index. On the other hand,
techniques and western blot analyses demonstrated that the higher levels of high-density lipoprotein levels which are
expression of phosphatidylinositol-3 kinase, serine-thre- supposed to be protective, were associated with an increased
onine kinase and their phosphorylated forms increased, duration of the disease. No other correlations were statisti-
while insulin receptor and insulin receptor substrate-1 were cally significant in this study (Cassani et al., 2013).
lower in the CA1 area of the hippocampus. The animals re- With regard to cardiometabolic and inflammatory factors,
ceived one of 3 doses of curcuma (400, 200 or 100 mg/kg per the study highlighted that body mass index, high-density
day) for 6 months, the most effective dose being the medium lipoprotein and C-reactive protein levels were inversely asso-
one among the treatment groups (Wang et al., 2017). ciated with AD incidence, while low-density lipoprotein and
Using the same curcuma doses (400, 200 or 100 mg/kg total cholesterol were positively associated with it (Larsson et
per day), a more recent study of double transgenic mice in- al., 2017).
vestigated both signaling pathways and glucose metabolism In a population-based autopsy study conducted by Dublin
regulation in the brain as well as the learning and memory et al. (2017), patients with atrial fibrillation were more likely
ability. Glucose metabolism was monitored using PET-CT to have AD, than those without atrial fibrillation, apparently
techniques with images that 3 months after the treatment because atrial fibrillation was not associated with AD neu-
showed a higher average glucose metabolism in the treated ropathological changes. However, none of these associations
group. Immunohistochemistry staining and western blot were statistically significant.
analyses showed up-regulation of insulin-like growth factor About 25% of all human body cholesterol is found in the
1, insulin receptor substrate 2, phosphatidylinositol-3 kinase, brain. Since cholesterol levels in brain influence the syn-
serine-threonine kinase and their phosphorylated forms but thesis, clearance and toxicity of amyloid-β peptide, a recent
decreased insulin receptor and insulin receptor substrate 1 study aimed to analyse the direct relationship between serum
(Matsuda et al., 2018). levels of cholesterol and amyloid-β deposition in the brain.
Data from the study showed that higher levels of low-density
Smoking and neurodegenerative diseases lipoprotein and lower levels high-density lipoprotein were
A recent analysis of the impact of 24 modifiable factors on both associated with greater deposition of brain amyloid, in-
the incidence of AD suggested an association between AD dependently of Apo E genotype (Reed et al., 2014).
and education i.e., genetically predicted higher educational A recent study followed the prevalence of cardio-metabolic
attainment was associated with fewer AD cases. Regarding factors in a group of 58 patients diagnosed with amyotrophic
lifestyles and dietary factors, the results for smoking, coffee lateral sclerosis (ALS) compared to the general population.
consumption and 25(OH) vitamin D were significantly as- ALS patients expressed a good cardiometabolic profile,
sociated with AD as follows: higher numbers of cigarettes with heart rate, blood pressure, PR and QT intervals in the
smoked gave lower odds for AD, higher 25(OH) vitamin normal range. Body mass index analysis revealed that there
D concentrations gave lower odds for AD and higher con- were fewer obese women and more men within the normal
sumption of coffee gave higher odds for AD (Larsson et al., body mass index interval in the ALS group compared to the
2017). general population. Both of these were statistically signifi-
cant. Dyslipidaemia was less frequent and a higher number
Frontotemporal dementia and alcohol, tobacco and coffee of individuals never smoked in the ALS cohort than in the
abuse general population (Timmins et al., 2017).
A multicentre case-control retrospective study analysed al-
cohol, tobacco and coffee consumption among 151 patients Dementia, stroke and glucose metabolism
with frontotemporal dementia and their matching controls. Pase and colleagues studied the Framingham Heart Study
There was no association between coffee and tobacco use Offspring cohort of 5124 volunteers, comprising 9 cycles of
and frontotemporal dementia, but alcohol intake decreased examination, every 4 years, starting in 1971 and concluding
the risk of frontotemporal dementia, with a significant re- in 2014. Regarding the sugar- and artificially-sweetened bev-
duction for current alcohol users. Furthermore, there was erages, the participants responded to a Harvard semi-quan-
an inverse correlation with the years of exposure to alcohol. titative food frequency questionnaire that included several
However, the amount of alcohol consumed was not given in types of beverage and their frequency of consumption in
the study (Tremolizzo et al., 2017). the previous year. The results show a correlation between
increased intake of artificially sweetened drinks and a higher
Cardio-metabolic and inflammatory factors and risk for stroke and dementia. Total sugary beverages or sugar
neurodegenerative diseases sweetened soft drinks were also associated with an increased
The aim of one study was to see the effects of cardio-meta- risk for dementia or stroke (Pase et al., 2017).
bolic factors on PD progression and survival. One hundred In 2017, a study was published that investigated the effects
and fifty patients were evaluated for body mass index, body of long-term administration of regular or long-acting insulin
fat percentage, waist circumference and impedance, serum on biomarkers of AD. The results of this randomized, dou-

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 Popa-Wagner A, Dumitrascu DI, Capitanescu B, Petcu EB, Surugiu R, Fang WH, Dumbrava DA (2020) Dietary habits, lifestyle factors and
neurodegenerative diseases. Neural Regen Res 15(3):394-400. doi:10.4103/1673-5374.266045

ble-blind, placebo-controlled study showed that the regular had better functional progression than did patients in other
insulin-treated group had improved memories after two weight categories (Burke et al., 2014).
months of treatment. No significant effects were observed in Yet another study that included 510 patients with transient
the long-acting insulin treated group (Craft et al., 2017). ischemic attack, showed that excess adiposity increases the
A prospective cohort study over 19 months followed 450 risk of severe disability after ischemic stroke. Contradictory
sporadic amyotrophic lateral sclerosis patients, 223 of whom results were reported in a study from 2007, showing that
died. The baseline included the lab findings for HbA1c and functional improvement was better in patients of normal
fasting blood glucose at the first meeting. A higher risk of weight than that in overweight/obese patients (Razinia et al.,
mortality was associated with increased baseline levels of 2007).
HbA1c, with a direct correlation between them, each addi- More recently, in a large retrospective cohort study from
tional unit (%) of HbA1c augmenting the risk of mortality by the Danish Stroke Register, 53,812 patients were analysed for
50%. No significant association was found between fasting correlations between obesity and age, sex, stroke severity, body
blood glucose levels and the risk of mortality, even though a mass index, cardiovascular profile, stroke subtype, and so-
similar trend was observed (Wei et al., 2017). cioeconomic status. Although stroke incidence was higher in
A study conducted on data from the Danish Registers younger age patients with higher body mass index, a clear cor-
system showed a protective association between prior diabe- relation could not be found in favour of the obesity paradox.
tes diagnosis and ALS. Obesity in unadjusted and adjusted Finally, still another study on 451 patients hospitalized for
models for other risk factors showed the same correlation, ischemic stroke found no correlation between body mass
but when diabetes was taken into consideration, the asso- index on admission and functional recovery on discharge
ciation was weaker and no longer significant. This does not (Tanizaki et al., 2000; Downes and Crack, 2010). Thus, it is
apply for diabetes, which remains protective regardless of risky to conclude that there is a protective effect of obesity
the obesity indicator. No significant association was ob- alone on functional recovery after stroke. However, since
served between hypercholesterolaemia or hyperlipidaemia patients with high body mass index seemed to have had less
and ALS diagnosis (Kioumourtzoglou et al., 2015). A study severe strokes (Ryu et al., 2011), it seems that the association
on data from the Swedish Patient Register found an inverse between higher body mass index and favourable functional
association between prior diabetes diagnosis and ALS, with recovery might be influenced by stroke severity and some
similar results after adjusting for socioeconomic status and degree of adiposity is necessary to prevent severe disability
education. The association was powerful for the noninsulin in stroke survivors (Chiquete et al., 2010).
dependent cases, but not for the insulin dependent ones, Using a C57B6/J mouse model maintained on normal or
which also correlated with age at diabetes diagnosis. An high fat diets with different levels of testosterone, Jayaraman
inverse correlation was observed for older individuals, i.e., et al. (2014) demonstrated that testosterone depletion ex-
in the under 50 years old group insulin dependent diabetes acerbates the negative effects on both metabolic and proin-
implies a higher risk for ALS (Mariosa et al., 2015). flammatory responses in the diet-induced obesity group.

Obesity, inflammation and rehabilitation odds in stroke Caloric restriction and rehabilitation odds in stroke
patients patients
The obesity paradox has been described as an inverse rela- Caloric restriction is an important promoter of autopha-
tionship between body mass index and mortality in stroke gy process and previous studies have demonstrated that
patients (Olsen et al., 2008; Towfighi and Ovbiagele, 2009; non-pharmaceutical intervention can contribute to life-span
Ovbiagele et al., 2011; Ryu et al., 2011; Vemmos et al., 2011; extension in various organisms (Bishop and Guarente, 2007;
Andersen and Olsen, 2015). Thus, a cohort study from the Colman et al., 2009). Some recent studies reported positive
China National Stroke Registry analyzed the relationship effects of caloric restriction on primates by lowering age-re-
between body mass index, mortality and post-stroke func- lated mortality and the incidence of age-related diseases
tional recovery at 3 months after disease onset in 10,905 (Colman et al., 2009). In vivo animal models also suggest
patients with acute ischemic stroke. Favourable functional that caloric restriction reduces the incidence of AD and PD
recovery was seen in 52.4% of underweight (body mass in- (Fontana et al., 2010; Hutchison and Mattson, 2010).
dex 18.5 kg/m2), 55% of normal weight (body mass index
18.5–22.9 kg/m2), 61% of overweight (body mass index 23– Metabolic syndrome and neuroregeneration
27.4 kg/m2), 59,2% of obese (27.5–32.4 kg/m2) and 60.3% Dietary and life habits along with food abundance and high
of severely obese (body mass index > 32.5 kg/m2) stroke income can lead to hypothalamus-mediated energy imbal-
survivors. Indeed, obesity, but not severe obesity, showed a ance and weight gain. At the molecular level, hypothalamic
protective trend in terms of 3-month functional recovery in O-GlcNAc transferase, which is a known intracellular sensor
the AIS survivors. Severe obesity was associated with higher of glucose metabolism catalysing the transfer of β-N-acetyl-
mortality at 3 months after stroke (Zhao et al., 2014). glucosamine from uridine-diphosphate-β-N-acetylglucos-
Another study has focused on the effect of body mass amine to the hydroxyl group of serine or threonine residues
index on stroke rehabilitation in 819 patients admitted to of nucleocytoplasmic proteins, controls body weight. In an
an acute rehabilitation hospital. Again, overweight patients experimental study, it could be shown that O-β-N-acetyl-

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Popa-Wagner A, Dumitrascu DI, Capitanescu B, Petcu EB, Surugiu R, Fang WH, Dumbrava DA (2020) Dietary habits, lifestyle factors and
neurodegenerative diseases. Neural Regen Res 15(3):394-400. doi:10.4103/1673-5374.266045

glucosamine transferase knock out exacerbated obesity and tion in the group undergoing moderate-intensity physical
insulin resistance induced by a high-fat diet in adult mice. activity compared with a healthy education group (Stephen
The feeding behaviour was accompanied by neuronal cell et al., 2017).
death including leptin receptor-expressing neurones, in the More recent studies found a positive effect of 6 weeks
hypothalamus (Dai et al., 2018). aerobic exercise on functional ability compared to AD indi-
Moran et al. (2015) examined if there was a link between viduals versus the groups undergoing non-aerobic stretching
in vivo neurodegeneration biomarkers and T2DM. To this and tonic control program. Aerobic training was associated
end they investigated a cohort of 124 patients with T2DM with an increased performance in a 6-minute walking test
and 692 controls. They found that there was a statistically as compared to control groups. Results from this study also
significant association between T2DM and p-tau protein lev- showed an association between changes in peak VO2 and
els in cerebrospinal fluid. changes in memory composite score with changes in bilater-
Chronic hyperglycemia in DM may lead to impaired al hippocampal volume (Morris et al., 2017).
neurogenesis and cognition deficits (Yu et al., 2019). The
underlying mechanism could be long noncoding RNA (ln- Conclusions
cRNA)-induced apoptosis of hippocampal neurons. LncRNA Lifestyle including high sugar diets, alcohol and tobacco ad-
H19, noncoding RNAs with lengths greater than 200 nucleo- diction or high fat diets as well as some intrinsic factors such
tides, are implicated in development and growth control (Yu as ageing, neuroinflammation, brain injury and oxidative
et al., 2019). A more recent study has shown that lncRNA stress, negatively influence the onset, severity and duration
H19 were upregulated in an experimental model of DM and of neurodegenerative diseases (Figure 1). Fortunately, there
induced apoptosis of hippocampal neurones by stimulating are several healthy dietary components such as polyunsatu-
methylation in the promoter region of the IGF2 gene. At the rated fatty acids and the anti-oxidants curcumin, resveratrol,
same time, lncRNA H19 increased the expression of the an- blueberry polyphenols, sulphoraphane, salvionic acid as well
ti-apoptotic factor Bcl-2 (Gao et al., 2014). as caloric restriction and physical activity which may coun-
teract ageing and associated neurodegenerative diseases via
Physical activity and neurodegenerative protection increased autophagy (Fîlfan et al., 2017; Madeo et al., 2018)
Stephen et al. (2017) reviewed the specific literature in order or increased neurogenesis in the adult brain (Table 1).
to investigate the association between AD and physical activ-
ity. Since AD is a multifactorial pathology, focusing on phys- Author contributions: Literature on dietary habits: DID, BC; literature
ical activity only in AD prevention has shown no beneficial on the lifestyle section: EBP and RS; literature on neurodegenerative dis-
results. Previous studies which included single lifestyle factor eases: DAD; manuscript design and editing: APW and WHF. All authors
approved the final manuscript.
changes - physical activity (Ball et al., 2002; Lautenschlageret Conflicts of interest: The authors declare no conflicts of interest.
al., 2008; Sink et al., 2015), management of cardiovascular Financial support: None.
factors (Qiu et al., 2005; Ruitenberg et al., 2005) and diet Copyright license agreement: The Copyright License Agreement has
(Martínez-Lapiscina et al., 2013) showed no or little benefit. been signed by all authors before publication.
Plagiarism check: Checked twice by iThenticate.
The LIFE study showed no improvement in cognitive func- Peer review: Externally peer reviewed.

Figure 1 Prodegeneration factors

including ageing, obesity and unhealthy
diets could be balanced by physical
activity, caloric restriction, and
anti-oxidants to mitigate the onset,
severity and duration of
neurodegenerative diseases.
AD: Alzheimer’s disease.

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 Popa-Wagner A, Dumitrascu DI, Capitanescu B, Petcu EB, Surugiu R, Fang WH, Dumbrava DA (2020) Dietary habits, lifestyle factors and
neurodegenerative diseases. Neural Regen Res 15(3):394-400. doi:10.4103/1673-5374.266045

Table 1 The impact of life style and the severity of neurodegenerative Craft S, Claxton A, Baker LD, Hanson AJ, Cholerton B, Trittschuh EH,
diseases Dahl D, Caulder E, Neth B, Montine TJ, Jung Y, Maldjian J, Whitlow
C, Friedman S (2017) Effects of regular and long-acting insulin on
Factor AD T2DM Stroke PD ALS cognition and Alzheimer’s disease biomarkers: A pilot clinical trial. J
Physical activity +++ + ? + ? Alzheimers Dis 57:1325-1334.
Calorie restriction ++ ++ + ? ? Dai CL, Gu JH, Liu F, Iqbal K, Gong CX (2018) Neuronal O-GlcNAc
transferase regulates appetite, body weight, and peripheral insulin
Alcohol consumption – ++ – + –
resistance. Neurobiol Aging 70:40-50.
Fatty Diet ++ + – –
Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet
Iron – – – + –
371:1612-1623.
Oxidative stress – + – + +
Downes CE, Crack PJ (2010) Neural injury following stroke: are Toll-
Trace elements – – – + – like receptors the link between the immune system and the CNS? Br
Polyunsaturated fatty acids – – – – – J Pharmacol 160:1872-1888.
Smoking – – ? – – Dublin S, Anderson ML, Heckbert SR, Hubbard RA, Sonnen JA, Crane
Coffee + – – – – PK, Montine TJ, Larson EB (2014) Neuropathologic changes associ-
High HDL-C – – – + – ated with atrial fibrillation in a population-based autopsy cohort. J
Low HDL + – – – – Gerontol A Biol Sci Med Sci 69:609-615.
High LDL + + + – – Feng HL, Dang HZ, Fan H, Chen XP, Rao YX, Ren Y, Yang JD, Shi J,
Sugary beverages – + + – – Wang PW, Tian JZ (2016) Curcumin ameliorates insulin signalling
pathway in brain of Alzheimer’s disease transgenic mice. Int J Immu-
AD: Alzheimer’s disease; ALS: amyotrophic lateral sclerosis; HDL: nopathol Pharmacol 29:734-741.
high-density lipoprotein; HDL-C: high-density lipoprotein cholesterol;
Fîlfan M, Sandu RE, Zăvăleanu AD, GreşiŢă A, Glăvan DG, Olaru DG,
LDL: low-density lipoprotein; PD: Parkinson’s disease; T2DM: type 2
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from yeast to humans. Science 328:321-326.
distributed under the terms of the Creative Commons Attribution-Non-
Commercial-ShareAlike 4.0 License, which allows others to remix, tweak, Gao Y, Wu F, Zhou J, Yan L, Jurczak MJ, Lee HY, Yang L, Mueller M,
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