Major neurocognitive disorder (MND) is a term that has been incorporated in DSM-5 to replace the term dementia. MND is a clinical syndrome characterized by global cognitive decline from the previous level of functioning as evidenced in the loss of one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptomotor, or social cognition). Occurring in clear sensorium, this decline interferes with the individual’s ability to be independent. MND is a public health issue with significant impact on patients, their families, and the community. Dementia is already an epidemic in the developed countries (Murray and Lopez, The Lancet, 349(9064):1498–1504, 1997). In more than 50% of cases of major neurocognitive disorders, Alzheimer’s disease is the cause (Alzheimer’s Association 2011). The pathology of AD is clearly defined to consist of neuritic plaques (NP), neurofibrillary tangles (NFT), and subsequent neuronal loss, which are present in a typical distribution in the brains of the afflicted patients. The two most common risk factors for AD are advanced age and family history of dementia.
The following case illustrates complex presentation in a female patient with early onset of symptoms from around 49 years of age. The genetic factors and clinical, ethical, and legal challenges will be illustrated.
This is a preview of subscription content, log in to check access.
“The authors have nothing to disclose.”
The Alzheimer Disease and Frontotemporal Dementia Mutation Database. Available online www.molgen.ua.ac.be/ADmutations, provides up-to-date information on various genes involved in AD.
Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease. Cereb Cortex. 1991;1(1):103–16.CrossRefPubMedGoogle Scholar
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.CrossRefGoogle Scholar
Breitner JC, Murphy EA, Folstein MF, Magruder-Habib K. Twin studies of Alzheimer’s disease: an approach to etiology and prevention. Neurobiol Aging. 1990;11(6):641–8.CrossRefPubMedGoogle Scholar
Breitner JCS, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, et al. APOE-ε4 count predicts age when prevalence of AD increases, then declines the cache county study. Neurology. 1999;53(2):321.CrossRefPubMedGoogle Scholar
Burlá C, Pessini L, Siqueira JE, Nunes R. Aging and Alzheimer’s disease: reflections on the loss of autonomy and the challenges of care. Revista Bioética. 2014;22(1):85–93.CrossRefGoogle Scholar
Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.CrossRefPubMedGoogle Scholar
Clarfield AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med. 2003;163(18):2219–29.CrossRefPubMedGoogle Scholar
Derence K. Dementia-specific respite: the key to effective caregiver support. N C Med J. 2005;66(1):48–51.PubMedGoogle Scholar
Drzezga A, Grimmer T, Henriksen G, Mühlau M, Perneczky R, Miederer I, et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology. 2009;72(17):1487–94.CrossRefPubMedGoogle Scholar
Greenberg SM, Vonsattel JP, Segal AZ, Chiu RI, Clatworthy AE, Liao A, et al. Association of apolipoprotein E ϵ2 and vasculopathy in cerebral amyloid angiopathy. Neurology. 1998;50(4):961–5.CrossRefPubMedGoogle Scholar
Jongsma K, van de Vathorst S. Advance directives in dementia research: the opinions and arguments of clinical researchers− an empirical study. Research ethics. 2015;11(1):4–14.CrossRefGoogle Scholar
Hope T, Savulescu J, Hendrick J. Medical ethics and law: the core curriculum. London: Churchill Livingstone/Elsevier; 2003.Google Scholar
Jellinger KA, Paulus W, Wrocklage C, Litvan I. Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer’s disease. Eur J Neurol. 2001;8(6):707–10.CrossRefPubMedGoogle Scholar
Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey–Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review) Report of the quality standards subcommittee of the american academy of neurology. Neurology. 2001;56(9):1143–53.CrossRefPubMedGoogle Scholar
Larson EB, Shadlen MF, Wang L, McCormick WC, Bowen JD, Teri L, Kukull WA. Survival after initial diagnosis of Alzheimer disease. Ann Intern Med. 2004;140(7):501–9.CrossRefPubMedGoogle Scholar
Lockhart A. Imaging Alzheimer’s disease pathology: one target, many ligands. Drug Discov Today. 2006;11(23):1093–9.CrossRefPubMedGoogle Scholar
Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M, et al. Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med. 2016;8(10):1184–96.CrossRefPubMedPubMedCentralGoogle Scholar
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease report of the NINCDS-ADRDA work group* under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology. 1984;34(7):939.CrossRefPubMedGoogle Scholar
Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, et al. National institute on aging–Alzheimer’s association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol. 2012;123(1):1–11.CrossRefPubMedGoogle Scholar
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global burden of disease study. Lancet. 1997;349(9064):1498–504.CrossRefPubMedGoogle Scholar
Ranginwala NA, Hynan LS, Weiner MF, White CL. Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry. 2008;16(5):384–8.CrossRefPubMedGoogle Scholar
Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology. 2002;58(11):1615–21.CrossRefPubMedGoogle Scholar