Advertisement

Canine Cognitive Dysfunction

Pathophysiology, Diagnosis, and Treatment
Published:March 05, 2019DOI:https://doi.org/10.1016/j.cvsm.2019.01.013

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Veterinary Clinics: Small Animal Practice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Landsberg G.M.
        • Nichol J.
        • Araujo J.A.
        Cognitive dysfunction syndrome: a disease of canine and feline brain aging.
        Vet Clin Small Anim. 2012; 42: 749-768
        • Vite C.H.
        • Head E.
        Aging in the canine and feline brain.
        Vet Clin Small Anim. 2014; 44: 1113-1129
        • Chapagain D.
        • Range F.
        • Huber L.
        • et al.
        Cognitive aging in dogs.
        Gerontology. 2018; 64: 165-171
        • Dewey C.W.
        Encephalopathies: disorders of the brain.
        in: Dewey C.W. da Costa R.C. Practical guide to canine and feline neurology. 3rd edition. Wiley-Blackwell, Ames (IA)2016: 141-236
        • Van der Flier W.M.
        • Skoog I.
        • Schneider J.A.
        • et al.
        Vascular cognitive impairment.
        Nat Rev Dis Primers. 2018; https://doi.org/10.1038/nrdp2018.3
        • Rofina J.E.
        • van Ederen A.M.
        • Toussaint M.J.M.
        • et al.
        Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer’s disease.
        Brain Res. 2006; 1069: 216-226
        • Weinstein J.D.
        A new direction for Alzheimer’s research.
        Neural Regen Res. 2018; 13: 190-193
        • Macdonald R.
        • Barnes K.
        • Hastings C.
        • et al.
        Mitochondrial abnormalities in Parkinson’s disease and Alzheimer’s disease: can mitochondria be targeted therapeutically?.
        Biochem Soc Trans. 2018; 46: 891-909
        • Ridge P.G.
        • Kauwe J.S.K.
        Mitochondria and Alzheimer’s disease: the role of mitochondrial genetic variation.
        Curr Genet Med Rep. 2018; 6: 1-10
        • Mullins R.
        • Reiter D.
        • Kapogiannis D.
        Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer’s brain.
        Ann Clin Transl Neurol. 2018; 5: 262-272
        • Schutt T.
        • Helboe L.
        • Pedersen L.O.
        • et al.
        Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer’s disease: a translational study of neuropathological and inflammatory markers.
        J Alzheimers Dis. 2016; 52: 433-449
        • Salvin H.E.
        • McGreevy P.D.
        • Sachdev P.S.
        • et al.
        Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs.
        Vet J. 2010; 184: 277-281
        • Nielson J.C.
        • Hart B.L.
        • Cliff K.D.
        • et al.
        Prevalence of behavioral changes associated with age-related cognitive impairment in dogs.
        J Am Vet Med Assoc. 2001; 218: 1787-1791
        • Azkona G.
        • Garcia-Belenguer S.G.
        • Chacon G.
        • et al.
        Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs.
        J Small Anim Pract. 2009; 50: 87-91
        • Schutt T.
        • Toft N.
        • Berendt M.
        Cognitive dysfunction, progression of age-related behavioral changes, biomarkers, and survival in dogs more than 8 years old.
        J Vet Intern Med. 2015; 29: 1569-1577
        • Head E.
        • Pop V.
        • Sarsoza F.
        • et al.
        Amyloid β-peptide and oligomers in the brain and CSF of aged canines.
        J Alzheimers Dis. 2010; 20: 637-646
        • Borras D.
        • Ferrer I.
        • Pumarola M.
        Age-related changes in the brain of the dog.
        Vet Pathol. 1999; 36: 202-211
        • Tapp P.D.
        • Siwak C.T.
        • Gao F.Q.
        • et al.
        Frontal lobe volume, function, and β-amyloid pathology in a canine model of aging.
        J Neurosci. 2004; 24: 8205-8213
        • Lee G.S.
        • Jeong Y.W.
        • Kim J.J.
        • et al.
        A canine model of Alzheimer’s disease generated by overexpressing a mutated human amyloid precursor protein.
        Int J Mol Med. 2014; 33: 1003-1012
        • Cummings B.J.
        • Head E.
        • Afagh A.J.
        • et al.
        β-amyloid accumulation correlates with cognitive dysfunction in the aged canine.
        Neurobiol Learn Mem. 1996; 66: 11-23
        • Ozawa M.
        • Chambers J.K.
        • Uchida K.
        • et al.
        The relation between canine cognitive dysfunction and age-related brain lesions.
        Pathology. 2016; 78: 997-1006
        • Sanchez M.P.
        • Garcia-Cabrero A.M.
        • Sanchez-Elexpuru G.
        • et al.
        Tau-induced pathology in epilepsy and dementia: notions from patients and animal models.
        Int J Mol Sci. 2018; https://doi.org/10.3390/ijms19041092
        • Sorrentino V.
        • Romani M.
        • Mouchiroud L.
        • et al.
        Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity.
        Nature. 2017; 552: 187-193
        • Cisternas P.
        • Inestrosa N.C.
        Brain glucose metabolism: role of Wnt signaling in the metabolic impairment in Alzheimer’s disease.
        Neurosci Biobehav Rev. 2017; 80: 316-328
        • Borghys H.
        • Van Broeck B.
        • Dhuyvetter D.
        • et al.
        Young to middle-aged dogs with high amyloid-β levels in cerebrospinal fluid are impaired on learning in standard cognition tests.
        J Alzheimers Dis. 2017; 56: 763-774
        • Fast R.
        • Schutt T.
        • Toft N.
        • et al.
        An observational study with long-term follow-up of canine cognitive dysfunction: clinical characteristics, survival, and risk factors.
        J Vet Intern Med. 2013; 27: 822-829
        • Katina S.
        • Farbakova J.
        • Madari A.
        • et al.
        Risk factors for canine cognitive dysfunction syndrome in Slovakia.
        Acta Vet Scand. 2017; https://doi.org/10.1186/s13028-016-0196-5
        • Vrinda M.
        • Arun S.
        • Srikumar B.N.
        • et al.
        Temporal lobe epilepsy-induced neurodegeneration and cognitive deficits: implications for aging.
        J Chem Neuroanat. 2018; https://doi.org/10.1016/j.chemneu.2018.02.005
        • Packer R.M.A.
        • McGreevy P.D.
        • Salvin H.E.
        • et al.
        Cognitive dysfunction in naturally occurring canine epilepsy.
        PLoS One. 2018; https://doi.org/10.1371/journal.pone.0192182
        • Cretin B.
        Pharmacotherapeutic strategies for treating epilepsy in patients with Alzheimer’s disease.
        Expert Opin Pharmacother. 2018; 11: 1201-1209
        • Harun A.
        • Oh E.S.
        • Bigelow R.T.
        • et al.
        Vestibular impairment in dementia.
        Oto Neurotol. 2016; 8: 1137-1142
        • Gonzalez-Martinez A.
        • Rosado B.
        • Pesini P.
        • et al.
        Effect of age and severity of cognitive dysfunction on two simple tasks in pet dogs.
        Vet J. 2013; 198: 176-181
        • Marek M.
        • Horyniecki M.
        • Fraczek M.
        • et al.
        Leukoaraiosis-new concepts and modern imaging.
        Pol J Radiol. 2018; 83: e76-e81
        • Scarpante E.
        • Cherubini G.B.
        • de Stefani A.
        • et al.
        Magnetic resonance imaging features of leukoaraiosis in elderly dogs.
        Vet Radiol Ultrasound. 2017; 58: 389-398
        • Hasegawa D.
        • Yayoshi N.
        • Fujita Y.
        • et al.
        Measurement of interthalamic adhesion thickness as a criteria for brain atrophy in dogs with and without cognitive dysfunction (dementia).
        Vet Radiol Ultrasound. 2005; 46: 452-457
        • Noh D.
        • Choi S.
        • Choi H.
        • et al.
        Evaluation of interthalamic adhesion size as an indicator of brain atrophy in dogs with and without cognitive dysfunction.
        Vet Radiol Ultrasound. 2017; 58: 581-587
        • Charidimou A.
        • Boulouis G.
        • Gurol M.E.
        • et al.
        Emerging concepts in sporadic cerebral amyloid angiopathy.
        Brain. 2017; 140: 1829-1840
        • Parkes I.
        • Chintawar S.
        • Cader M.Z.
        Neurovascular dysfunction in dementia-human cellular models and molecular mechanisms.
        Clin Sci. 2018; 132: 399-418
        • Yamada M.
        Brain hemorrhages in cerebral amyloid angiopathy.
        Semin Thromb Hemost. 2013; 39: 955-962
        • Ungvari Z.
        • Tarantini S.
        • Kirkpatrick A.C.
        • et al.
        Cerebral microhemorrhages: mechanisms, consequences, and prevention.
        Am J Physiol Heart Circ Physiol. 2017; 312: H1128-H1143
        • Jakel L.
        • Van Nostrand W.E.
        • Nicoll J.A.R.
        • et al.
        Animal models of cerebral amyloid angiopathy.
        Clin Sci. 2017; 131: 2469-2488
        • Hodshon A.W.
        • Hecht S.
        • Thomas W.B.
        Use of the T2*-weighted gradient recalled echo sequence for magnetic resonance imaging of the canine and feline brain.
        Vet Radiol Ultrasound. 2014; 55: 599-606
        • Kerwin S.C.
        • Levine J.M.
        • Budke C.M.
        • et al.
        Putative cerebral microbleeds in dogs undergoing magnetic resonance imaging of the head: a retrospective study of demographics, clinical associations, and relationship to case outcome.
        J Vet Intern Med. 2017; 31: 1140-1148
        • Landsberg G.M.
        • DePorter T.
        • Araujo J.A.
        Clinical signs and management of anxiety, sleeplessness, and cognitive dysfunction in the senior pet.
        Vet Clin Small Anim. 2011; 41: 565-590
        • Solfrizzi V.
        • Custodero C.
        • Lozupone M.
        • et al.
        Relationships of dietary patterns, foods, and micro-and macronutrients with Alzheimer’s disease and late-life cognitive disorders: a systematic review.
        J Alzheimers Dis. 2017; 59: 815-849
        • Pistollato F.
        • Iglesias R.C.
        • Ruiz R.
        • et al.
        Nutritional patterns associated with the maintenance of neurocognitive functions and the risk of dementia and Alzheimer’s disease: a focus on human studies.
        Pharmacol Res. 2018; 131: 32-43
        • Gandy S.
        • Bartfai T.
        • Lees G.V.
        • et al.
        Midlife interventions are critical in prevention, delay, or improvement of Alzheimer’s disease and vascular cognitive impairment and dementia.
        F1000Res. 2017; https://doi.org/10.12688/f1000research.11140.1
        • Ravi S.K.
        • Narasingappa R.B.
        • Vincent B.
        Neuro-nutrients as anti-Alzheimer’s disease agents: a critical review.
        Crit Rev Food Sci Nutr. 2018; https://doi.org/10.1080/10408398.2018.1481012
        • Milgram N.W.
        • Zicker S.C.
        • Head E.
        • et al.
        Dietary enrichment counteracts age-associated cognitive dysfunction in canines.
        Neurobiol Aging. 2002; 23: 737-745
        • Milgram N.W.
        • Head E.
        • Muggenburg B.
        • et al.
        Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy.
        Neurosci Biobehav Rev. 2002; 26: 679-695
        • Milgram N.W.
        • Head E.
        • Zicker S.C.
        • et al.
        Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs.
        Exp Gerontol. 2004; 39: 753-765
        • De Roos B.
        • Duthie G.G.
        Role of dietary pro-oxidants in the maintenance of health and resilience to oxidative stress.
        Mol Nutr Food Res. 2015; 59: 1229-1248
        • Dodd C.E.
        • Zicker S.C.
        • Jewell D.E.
        • et al.
        Can a fortified food affect the behavioral manifestations of age-related cognitive decline in dogs?.
        Vet Med. 2003; 98: 396-408
        • Rebello C.J.
        • Keller J.N.
        • Liu A.G.
        • et al.
        Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: a randomized controlled trial.
        BBA Clin. 2015; 3: 123-125
        • Pan Y.
        • Larson B.
        • Araujo J.A.
        • et al.
        Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs.
        Br J Nutr. 2010; 103: 1746-1754
        • Courchesne-Loyer A.
        • St-Pierre V.
        • Hennebelle M.
        • et al.
        Ketogenic response to cotreatment with bezafibrate and medium chain triacylglycerolsin healthy humans.
        Nutrition. 2015; 31: 1255-1259
        • Law T.H.
        • Volk H.A.
        • Pan Y.
        • et al.
        Metabolic perturbations associated with the consumption of a ketogenic medium chain TAG diet in dogs with idiopathic epilepsy.
        Br J Nutr. 2018; 120: 484-487
        • Augustin K.
        • Aziza K.
        • Williams S.
        • et al.
        Mechanism of action for medium-chain triglyceride ketogenic diets in neurological and metabolic disorders.
        Lancet Neurol. 2018; 17: 84-93
        • Nonaka Y.
        • Takagi T.
        • Inai M.
        • et al.
        Lauric acid stimulates ketone body production in the KT-5 astrocyte cell line.
        J Oleo Sci. 2016; 65: 693-699
        • Nafar F.
        • Clarke J.P.
        • Mearow K.M.
        Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.
        Neurochem Int. 2017; 105: 64-79
        • Liu K.
        • Lin H.H.
        • Pi R.
        • et al.
        Research and development of anti-Alzheimer’s disease drugs: an update from the perspective of technology flows.
        Expert Opin Ther Pat. 2018; 28: 341-350
        • Evans J.G.
        • Wilcock G.
        • Birks J.
        Evidence-based pharmacotherapy of Alzheimer’s disease.
        Int J Neuropsychopharmacol. 2004; 7: 351-369
        • Milgram N.W.
        • Go I.
        • Head E.
        • et al.
        The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog.
        Neurochem Res. 1993; 18: 1211-1219
        • Ebadi M.
        • Brown-Borg H.
        • Ren J.
        • et al.
        Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases.
        Curr Drug Targets. 2006; 7: 1513-1529
        • Sanchez P.E.
        • Zhu L.
        • Verret L.
        • et al.
        Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model.
        Proc Natl Acad Sci U S A. 2012; https://doi.org/10.1073/pnas.1121081109
        • Stockburger C.
        • Miano D.
        • Baeumlisberger M.
        • et al.
        A mitochondrial role of SV2a protein in aging and Alzheimer’s disease: studies with levetiracetam.
        J Alzheimers Dis. 2016; 50: 201-215
        • Sanz-Blasco S.
        • Pina-Crespo J.C.
        • Zhang X.
        • et al.
        Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes.
        Neuroreport. 2016; 27: 705-709
        • Reme C.A.
        • Dramard V.
        • Kern L.
        • et al.
        Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial.
        Vet Ther. 2008; 9: 69-82
        • Araujo J.A.
        • Landsberg G.M.
        • Milgram N.W.
        • et al.
        Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, Vitamin E, and pyridoxine.
        Can Vet J. 2008; 49: 379-385
        • Heath S.E.
        • Barabas S.
        • Craze B.G.
        Nutritional supplementation in cases of canine cognitive dysfunction-a clinical trial.
        Appl Anim Behav Sci. 2007; 105: 274-283
        • Milgram N.W.
        • Siwak-Tapp C.T.
        • Araujo J.
        • et al.
        Neuroprotective effects of cognitive enrichment.
        Ageing Res Rev. 2006; 5: 354-369
        • Guitar N.A.
        • Connelly D.
        • Nagamatsu L.S.
        • et al.
        Ageing Res Rev. 2018; 47: 159-167
        • Sobol N.A.
        • Dall C.H.
        • Hogh P.
        • et al.
        Change in fitness and the relation to change in cognition and neuropsychiatric symptoms after aerobic exercise in patients with mild Alzheimer’s disease.
        J Alzheimers Dis. 2018; 65: 137-145
        • Fang J.
        • Wang L.
        • Wu T.
        • et al.
        Network pharmacology-based study on the mechanism of action for herbal medicines in Alzheimer treatment.
        J Ethnopharmacol. 2016; https://doi.org/10.1016/j.jep.2016.11.034
        • Xu Q.Q.
        • Shan C.S.
        • Wang Y.
        • et al.
        Chinese herbal medicine for vascular dementia: a systematic review and meta-analysis of high-quality randomized controlled trials.
        J Alzheimers Dis. 2018; 62: 429-456
        • Howes M.R.
        • Fang R.
        • Houghton P.J.
        Effect of Chinese herbal medicine on Alzheimer’s disease.
        Int Rev Neurobiol. 2017; 135: 29-56
        • Dey A.
        • Bhattacharya R.
        • Mukherjee A.
        • et al.
        Natural products against Alzheimer’s disease: pharmaco-therapeutics and biotechnological interventions.
        Biotechnol Adv. 2017; 35: 178-216
        • Chang D.
        • Liu J.
        • Bilinski K.
        • et al.
        Herbal medicine for the treatment of vascular dementia: an overview of scientific evidence.
        Evid Based Complement Alternat Med. 2016; https://doi.org/10.1155/2016/7293626
        • Wang Z.Y.
        • Liu J.G.
        • Yang H.M.
        Pharmacological effects of active components of Chinese herbal medicine in the treatment of Alzheimer’s disease: a review.
        Am J Chin Med. 2016; 44: 1525-1541
        • Tewari D.
        • Stankiewicz A.M.
        • Mocan A.
        • et al.
        Ethnopharmacological approaches for dementia therapy and significance of natural products and herbal drugs.
        Front Aging Neurosci. 2018; 10: 1-24
        • Jiang Y.
        • Gao H.
        • Turdu G.
        Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer’s disease: a review.
        Bioorg Chem. 2017; 75: 50-61
        • Zhou X.
        • Cui G.
        • Tseng H.H.L.
        • et al.
        Vascular contributions to cognitive impairment and treatments with traditional Chinese medicine.
        Evid Based Complement Alternat Med. 2016; https://doi.org/10.1155/2016/9627258
        • Libro R.
        • Giacoppo S.
        • Rajan T.S.
        • et al.
        Natural phytochemicals in the treatment and prevention of dementia: an overview.
        Molecules. 2016; 21: 518
        • Wightman E.L.
        Potential benefits of phytochemicals against Alzheimer’s disease.
        Proc Nutr Soc. 2017; 76: 106-112
        • Hyde A.J.
        • May B.H.
        • Dong L.
        • et al.
        Herbal medicine for management of the behavioural and psychological symptoms of dementia (BPSD): a systematic review and meta-analysis.
        J Psychopharmacol. 2016; https://doi.org/10.1177/0269881116675515
        • Durairajan S.S.K.
        • Chirasani V.R.
        • Shetty S.G.
        • et al.
        Decrease in the generation of amyloid-β due to salvianolic acid B by modulating BACE1 activity.
        Curr Alzheimer Res. 2017; 14: 1229-1237
        • Lopresti A.L.
        Salvia (sage): a review of its potential cognitive-enhancing and protective effects.
        Drugs R D. 2017; 17: 53-64
        • Pang X.C.
        • Kang D.
        • Fang J.S.
        • et al.
        Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer’s disease.
        Chin J Nat Med. 2018; 16: 53-62
        • Shi J.
        • Ni J.
        • Lu T.
        • et al.
        Adding Chinese herbal medicine to conventional therapy brings benefits to patients with Alzheimer’s disease: a retrospective analysis.
        BMC Complement Altern Med. 2017; 17: 1-7
        • Zhang Y.
        • Lin C.
        • Zhang L.
        • et al.
        Cognitive improvement during treatment for mild Alzheimer’s disease with a Chinese herbal formula: a randomized controlled trial.
        PLoS One. 2015; https://doi.org/10.1371/journal.pone.0130353
        • Wang J.H.
        • Lei X.
        • Cheng X.R.
        • et al.
        LW-AFC, a new formula derived from Liuwei Dihaung decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice.
        Alzheimers Res Ther. 2016; https://doi.org/10.1186/s13195-0226-6
        • Huang Y.
        • Zhang H.
        • Yang S.
        • et al.
        Liuwei Dihuang decoction facilitates the induction of long-term potentiation (LTP) in senescence accelerated mouse/prone 8 (SAMP8) hippocampal slices by inhibiting voltage-dependent calcium channels (VDDCs) and promoting N-methyl-D-aspartate receptor (NMDA) receptors.
        J Ethnopharmacol. 2012; 140: 384-390
        • Steiner G.Z.
        • Yeung A.
        • Liu J.X.
        • et al.
        The effect of Sailoutong (SLT) on neurocognitive and cardiovascular function in healthy adults: a randomized, double-blind, placebo-controlled crossover pilot trial.
        BMC Complement Altern Med. 2016; https://doi.org/10.1186/s12906-016-0989-0
        • Liang J.
        • Li F.
        • Wei C.
        • et al.
        Rationale and design of a multicenter, phase 2 clinical trial to investigate the efficacy of traditional Chinese medicine sailuotong in vascular dementia.
        J Stroke Cerebrovasc Dis. 2014; 23: 2626-2634
        • Tian J.
        • Shi J.
        • Wei M.
        • et al.
        The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.
        Trials. 2016; 17: 281
        • Iwasaki K.
        • Kobayashi S.
        • Chimura Y.
        • et al.
        A randomized, double-blind, placebo-controlled clinical trial of the Chinese herbal medicine “ba wei di huang wan” in the treatment of dementia.
        J Am Geriatr Soc. 2004; 52: 1518-1521
        • Iwasaki K.
        • Satoh-Nakagawa T.
        • Maruyama M.
        • et al.
        A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients.
        J Clin Psychiatry. 2005; 66: 248-252
        • Park S.
        • Lee J.H.
        • Yang E.J.
        Effects of acupuncture on Alzheimer’s disease in animal-based research.
        Evid Based Complement Alternat Med. 2017; https://doi.org/10.1155/2017/6512520
        • Zhou S.
        • Dong L.
        • He Y.
        • et al.
        Acupuncture plus herbal medicine for Alzheimer’s disease: a systematic review and meta-analysis.
        Am J Chin Med. 2017; 45: 1327-1344
        • Lu Y.J.
        • Cai X.W.
        • Zhang G.F.
        • et al.
        Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer’s disease: a positron emission tomography study.
        Neural Regen Res. 2017; 12: 1159-1165
        • Jia Y.
        • Zhang X.
        • Yu J.
        • et al.
        Acupuncture for patients with mild to moderate Alzheimer’s disease: a randomized controlled trial.
        BMC Complement Altern Med. 2017; 17: 556
        • Liu W.
        • Zhuo P.
        • Li L.
        • et al.
        Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture.
        Free Radic Biol Med. 2017; 112: 174-190
        • Shin H.K.
        • Lee S.W.
        • Choi B.T.
        Modulation of neurogenesis via neurotrophic factors in acupuncture treatments for neurological diseases.
        Biochem Pharmacol. 2017; 141: 132-142
        • Kan B.H.
        • Yu J.C.
        • Zhao L.
        • et al.
        Acupuncture improves dendritic structure and spatial learning and memory ability of Alzheimer’s disease mice.
        Neural Regen Res. 2018; https://doi.org/10.4103/1673-5374.235292
        • Zheng W.
        • Su Z.
        • Liu X.
        • et al.
        Modulation of functional activity and connectivity by acupuncture in patients with Alzheimer disease as measured by resting-state fMRI.
        PLoS One. 2018; https://doi.org/10.1371/journal.pone.0196933
        • Shan Y.
        • Wang J.J.
        • Wang Z.Q.
        • et al.
        Neuronal specificity of acupuncture in Alzheimer’s disease and mild cognitive impairment patients: a functional MRI study.
        Evid Based Complement Alternat Med. 2018; https://doi.org/10.1155/2018/7619197
        • Ye Y.
        • Zhu W.
        • Wang X.R.
        • et al.
        Mechanisms of acupuncture on vascular dementia–a review of animal studies.
        Neurochem Int. 2017; 107: 204-210
        • Xiao L.Y.
        • Wang X.R.
        • Yang Y.
        • et al.
        Applications of acupuncture therapy in modulating plasticity of central nervous system.
        Neuromodulation. 2017; https://doi.org/10.1111/ner.12724
        • Leung M.C.
        • Yip K.K.
        • Ho Y.S.
        • et al.
        Mechanisms underlying the effect of acupuncture on cognitive improvement: a systematic review of animal studies.
        J Neuroimmune Pharmacol. 2014; 9: 492-507
        • Sutalangka C.
        • Wattanathorn J.
        • Muchimapura S.
        • et al.
        Laser acupuncture improves memory impairment in an animal model of Alzheimer’s disease.
        J Acupunct Meridian Stud. 2013; 6: 247-251