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Diabetes-Related Dementia

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Diabetes Mellitus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1128))

Abstract

Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as in Alzheimer disease (AD) and vascular dementia (VaD). Additionally, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than with AD pathology or cerebrovascular diseases. This type of dementia, not showing hypoperfusion in the parietotemporal lobe on SPECT or cerebrovascular lesions on MRI, was characterized by old age, high hemoglobin A1c level, long duration of diabetes, high frequency of insulin therapy, low frequency of apolipoprotein E4 carrier, less-severe medial temporal lobe atrophy, impaired attention and executive function, less-impaired word recall, and slow progression of cognitive impairment and might be referred to as “diabetes-related dementia” (DrD). 11C-Pittsburgh compound-B PET shows often negative or equivocal amyloid accumulation in the brain, indicating different from AD pathology. In addition to insulin resistance, elevated inflammatory cytokines, oxidative stress, and advanced glycation end products were associated with cognitive impairment in this type of dementia. Glycemic controls can improve some domains of cognitive function, such as attention and executive functions, in subjects with DrD. Frequencies of frailty and sarcopenia/dynapenia are significantly higher in DrD than in AD, indicating that geriatric interventions are necessary to improve clinical outcomes for patients with DrD. DrD can be considered as a controllable or modifiable dementia. The identification of DrD, as distinct from other types of dementia, may be necessary for considering appropriate therapy and prevention in clinical practice.

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References

  • Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: a systemic review. Lancet Neurol 5:64–74

    Article  Google Scholar 

  • Blaum CS, Xue QL, Tian J, Semba RD, Fried LP, Walston J (2009) Is hyperglycemia associated with frailty status in old women? J Am Geriatr Soc 57:840–847

    Article  Google Scholar 

  • Bonte FJ, Harris TS, Hynan LS, Bigio EH, White CL III (2006) Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation. Clin Nucl Med 31:376–378

    Article  Google Scholar 

  • Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, Chou MY, Chen LY, Hsu PS, Krairit O, Lee JS, Lee WJ, Lee Y, Liang CK, Limpawattana P, Lin CS, Peng LN, Satake S, Suzuki T, Won CW, Wu CH, Wu SN, Zhang T, Zeng P, Akishita M, Arai H (2014) Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 15:95–101

    Article  Google Scholar 

  • Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment. Arch Neurol 69:29–38

    Article  Google Scholar 

  • Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Gearing M, Grinberg LT, Hof PR, Hyman BT, Jellinger K, Jicha GA, Kovacs GG, Knopman DS, Kofler J, Kukull WA, Mackenzie IR, Masliah E, McKee A, Montine TJ, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White CL 3rd, Wisniewski T, Woltjer RL, Yamada M, Nelson PT (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766

    Article  CAS  Google Scholar 

  • Dougall NJ, Bruggink S, Ebmeier KP (2004) Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. Am J Geriatr Psychiatry 12:554–570

    Article  Google Scholar 

  • Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 149:351–356

    Article  CAS  Google Scholar 

  • Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group (2001) Cardiovascular Health Study Collaborative Research Group: frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med 56:M146–M156

    Article  CAS  Google Scholar 

  • Fukasawa R, Hanyu H, Sato T, Shimizu S, Koyama S, Kanetaka H, Sakurai H, Iwamoto T (2013) Subgroups of Alzheimer’s disease associated with diabetes mellitus based on brain imaging. Dement Geriatr Cogn Disord 35:280–290

    Article  Google Scholar 

  • Fukasawa R, Hanyu H, Namioka N, Hatanaka H, Sato T, Sakurai H (2014) Elevated inflammatory markers in diabetes-related dementia. Geriatr Gerontol Int 14:229–231. 2014

    Article  Google Scholar 

  • Fukasawa R, Hanyu H, Shimizu S, Kanetaka H, Sakurai H, Ishii K (2015) Identification of diabetes-related dementia: longitudinal perfusion SPECT and amyloid PET studies. J Neurol Sci 349:45–51

    Article  Google Scholar 

  • Hanyu H, Hirose D, Fukasawa R, Hatanaka H, Namioka N, Sakurai H (2015) Guidelines for the clinical diagnosis of diabetes mellitus-related dementia. J Am Geriatr Soc 63:1721–1722

    Article  Google Scholar 

  • Hanyu H, Fukasawa R, Shimizu S, Sakurai H, Ishii K, Shimada H, Higuchi M, Suhara T (2016) Amyloid and tau PET findings in diabetes-related dementia. Alzheimer Association International Conference 2016 (Toronto)

    Google Scholar 

  • Hatanaka H, Hanyu H, Fukasawa R, Sato T, Shimizu S, Sakurai H (2016) Peripheral oxidative stress markers in diabetes-related dementia. Geriatr Gerontol Int 16:1312–1318

    Article  Google Scholar 

  • Heneka MT, Fink A, Doblhammer G (2015) Effect of pioglitazone medication on the incidence of dementia. Ann Neurol 78:284–294

    Article  CAS  Google Scholar 

  • Hirose D, Hanyu H, Fukasawa R, Hatanaka H, Nanioka N, Okita M (2015) Circulating levels of advanced glycation end products in diabetes-related dementia. J Am Geriatr Soc 63:2196–2198

    Article  Google Scholar 

  • Hirose D, Hanyu H, Fukasawa R, Hatanaka H, Namioka N, Sakurai H (2016) Frailty in diabetes-related dementia. Geriatr Gerontol Int 16:653–655

    Article  Google Scholar 

  • Hirose D, Hanyu H, Fukasawa R, Namioka N, Hatanaka H, Sato T (2017) Diabetes-related dementia is associated with dynapenia, but not with sarcopenia. Geriatr Gerontol Int 17:175–177

    Article  Google Scholar 

  • Kalyani RR, Tian J, Xue QL, Walston J, Cappola AR, Fried LP, Brancati FL, Blaum CS (2012) Hyperglycemia is associated with the incidence of frailty and lower extremity mobility limitations in older women. J Am Geriatr Soc 60:1701–1707

    Article  Google Scholar 

  • Kopf D, Frolich L (2009) Risk of incident Alzheimer’s disease in diabetic patients: a systematic review of prospective trials. J Alzheimers Dis 16:677–685

    Article  Google Scholar 

  • Li W, Huang E (2016) An update on type 2 diabetes mellitus as a risk factor for dementia. J Alzheimers Dis 53:393–402

    Article  CAS  Google Scholar 

  • Manini TM, Clark BC (2012) Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci 67A:28–40

    Article  Google Scholar 

  • Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski QJ, Lee VMY, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, Kudo Y, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, Makoto Higuchi M (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79:1094–1108

    Article  CAS  Google Scholar 

  • Moran C, Beare R, Phan TG, Bruce DG, Callisaya ML, Srikanth V, Alzheimer’s Disease Neuroimaging Initiative (ADNI) (2015) Type 2 diabetes mellitus and biomarkers of neurodegeneration. Neurology 85:1123–1130

    Article  CAS  Google Scholar 

  • Risner ME, saunders AM, Altman JFB, Ormandy GC, Craft S, Foley IM, Zvartau-ind ME, Hosford DA, Roses AD (2006) Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharm J 6:222–224

    Google Scholar 

  • Roberts RO, Knopman DS, Cha RH, Mielke MM, Pankratz VS, Boeve BF, Kantarci K, Geda YE, Jack CR Jr, Petersen RC, Lowe VJ (2014) Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation. J Nucl Med 55:759–764

    Article  CAS  Google Scholar 

  • Robertson DA, Savva GM, Kenny AR (2013) Frailty and cognitive impairment – a review of the evidence and causal mechanisms. Ageing Res Rev 12:840–851

    Article  Google Scholar 

  • Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T (2011) Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer’s disease. Neurobiol Aging 32:1626–1633

    Article  CAS  Google Scholar 

  • Verdile G, Fuller SJ, Martins RN (2015) The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 84:22–38

    Article  CAS  Google Scholar 

  • Visser M, Deeg DJH, Lips P, Harris TB, Bouter LM (2000) Skeletal muscle mass and muscle strength in relation to lower-extremity performance in men and women. J Am Geriatr Soc 48:381–386

    Article  CAS  Google Scholar 

  • Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S (2005) Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone. A preliminary study. Am J Geriatr Psychiatry 13:950–958

    Google Scholar 

  • Yamada M (2003) Senile dementia of the neurofibrillary tangle type (tangle-only dementia): neuropathological criteria and clinical guidelines for diagnosis. Neuropathology 23:311–317

    Article  Google Scholar 

Download references

Acknowledgments

I am extremely grateful to Dr. K. Ishii from the Neuroimaging Center of Tokyo Metropolitan Institute of Gerontology and Dr. H. Shimada, Dr. M. Higuchi, and Dr. T. Suhara from the Molecular Imaging Center of National Institute of Radiological Sciences for PiB and PBB3 PET studies. I am also grateful to the medical editors from the Department of International Medical Communications of Tokyo Medical University for editing and reviewing the English manuscript. This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (c) No. 15K09326.

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Correspondence to Haruo Hanyu .

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Hanyu, H. (2019). Diabetes-Related Dementia. In: Nakabeppu, Y., Ninomiya, T. (eds) Diabetes Mellitus. Advances in Experimental Medicine and Biology, vol 1128. Springer, Singapore. https://doi.org/10.1007/978-981-13-3540-2_8

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