ArticlesLoss of Olfactory Function in Dementing Disease
Section snippets
Alzheimer’s disease (ad)
Alzheimer’s disease is a debilitating neurodegenerative disease afflicting more than 5 million Americans, most over the age of 60. For those that suffer the disease and for the families that provide their care, it represents a slow and inevitable deterioration of cognitive function, memory, personality, language function, and the essence of the person. At present there is no cure, and efforts to blunt the effects of the disease succeed in only a portion of patients and provide only temporary
Mechanism for olfactory dysfunction in ad
The appearance of neurofibrillary tangles in the transentorhinal and entorhinal regions of the brain is the initial event in AD 7, 8. From these areas, degeneration proceeds to include other temporal lobe structures, including the hippocampus and proneocortex. The orbital frontal cortex is also an early target of degeneration. The elegant work of Price et al. (46) indicated the presence of tangles in areas that mediate olfactory function, particularly the anterior olfactory nucleus, entorhinal
Olfactory functioning persons at risk for ad due to apoe4 allele status
Apolipoprotein E (APOE), a protein involved in lipid transport and production, is synthesized and transmitted throughout many organs in the body, including the CNS, and large amounts of the protein are found in the brain. The APOE gene has been localized at chromosome 19, locus C3 10, 42. There are three APOE alleles: ϵ2, ϵ3, and ϵ4; and three corresponding protein isoforms, with the most common isoform being APOE3. The APOE protein is found in increased amount in patients with AD, and
Decline in olfactory function over time in individuals with down’s syndrome (ds)
Family history of DS is a recognized risk factor for AD (21), and, conversely, the likelihood of Down’s Syndrome is increased by 2-1/2 times in persons with a family history of Alzheimer’s Disease (18). Genetic studies implicate chromosome 21 in both AD and DS (11). A number of studies have described Alzheimer’s like neuropathology in DS: plaques, neurofibrillary tangles, and granulovacular degeneration 2, 3, 25, 26, 27, 41, 43, 47, 59.As with AD, the neurons in layer II of entorhinal cortex
Sensitivity and specificity of olfactory measures
Thus, at this point we and others have demonstrated significant deficits in patients with AD, as well as in persons “at risk” for AD because of 1) indications of memory loss not sufficient for the diagnosis of AD and without disruption in daily function, or 2) by virtue of their genetic status (positive for the APOE4 allele). It is useful to consider the sensitivity (the ability of the test to correctly classify a patient as a patient) and specificity (the ability of the test to correctly
Acknowledgements
This research was supported by NIH Grants AG08203 and AG04085 from the National Institute on Aging. I am grateful to Dr. Robert Katzman, Dr. Leon Thal, Dr. David Salmon, Dr. Mark Bondi, and the UCSD ADRC for access to patients assessed for Alzheimer’s Disease and to Anna Bacon, Charlie D. Morgan, Jill Razani, Rani Nijjar, Leticia Acosta, Dr. Steven Nordin, and Spencer Wetter for their collaboration on these studies.
References (59)
- et al.
Morphological criteria for the recognition of Alzheimer’s disease and the distribution pattern of cortical changes related to this disorder
Neurobiol. Aging
(1994) - et al.
Frequency of stages of Alzheimer-related lesions in different age categories
Neurobiol. Aging
(1997) - et al.
Isolation, characterization, and mapping to chromosome 19 of the human apolipoprotein E gene
J. Biol. Chem.
(1985) - et al.
Development of the University of Pennsylvania Smell Identification TestA standardized microencapsulated test of olfactory function
Physiol. Behav.
(1984) - et al.
Olfactory identification deficits in Down’s syndrome and idiopathic mental retardation
Neuropsychologia
(1993) The neuropathological diagnosis of Alzheimer’s diseaseClinical-pathological studies
Neurobiol. Aging
(1997)- et al.
Olfactory detection and recognition in Alzheimer’s disease
Lancet
(1987) - et al.
Odor identificationThe blind are better
Physiol. Behav.
(1986) - et al.
Olfactory dysfunction in Down’s Syndrome
Neurobiol. Aging
(1996) - et al.
Olfactory thresholds are associated with degree of dementia in Alzheimer’s disease
Neurobiol. Aging
(1990)
Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jacob disease
Brain Res.
Apolipoprotein E polymorphism and Alzheimer’s disease
Lancet
The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease
Neurobiol. Aging
Apolipoprotein E is a relevant susceptibility gene that affects the rate of expression of Alzheimer’s disease
Neurobiol. Aging
Olfactory deficits and Alzheimer’s disease
Biol. Psychiatry
Olfactory deficits and Down’s syndrome
Biol. Psychiatry
Very early changes in olfactory functioning due to Alzheimer’s disease and the role of Apolipoprotein E in olfaction
Ann. NY Acad. Sci.
Neurofibrillary tangles, granulovacuolar degeneration and neuron loss in Down’s syndromeQuantitative comparison with Alzheimer’s dementia
Ann. Neurol.
The development of the pathologic changes of Alzheimer’s disease and senile dementia in patients with Down’s syndrome
Am. J. Pathol.
The association between quantitative measures of dementia and of senile change in gray matter of elderly subjects
Br. J. Psychiatry.
Episodic memory changes are associated with the APO-E ϵ4 allele in nondemented older adults
Neurology.
Allocortical involvement in Hungtington’s disease
Neuropathol. Appl. Neurobiol.
Gene dose of apolipoprotein type 4 allele and the risk of Alzheimer’s disease in late onset Families
Science
Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome)
Hum. Genet.
Olfactory dysfunction in Alzheimer’s disease
Chem. Senses
Smell identification abilityChanges with age
Science
The rhinologic evaluation of Alzheimer’s disease
Laryngoscope
Psychological testing in the differential diagnosis of dementias
Alzheimer’s disease, trisomy 21, and myeloproferative disordersAssociations suggesting a genetic diathesis
Science
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2021, Molecular Aspects of MedicineCitation Excerpt :They usually develop an age-dependent elevation of Aβ, with onset at 8 months of age and with Aβ-containing plaques occurring in the neocortex and HP by 10–16 months, and impairments of spatial and fear memory at 9–10 months. The author analyzed polySia-NCAM expression, especially in the OB (Guérin et al., 2009), because functional olfactory deficits associated with the earliest symptoms of AD were considered to be related to an alteration of neurogenesis, induced by a dysfunction of the LC/NA (locus coeruleus/noradrenaline) system (Hawkes, 2003; Mesholam et al., 1998; Murphy, 1999). Interestingly, Tg mice showed decreased polySia-expression in the OB.
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2018, Neurobiology of AgingCitation Excerpt :Alzheimer's disease (AD) is a progressive neurodegenerative disease wherein patients suffer from sensory, motor, progressive memory loss, and cognitive decline, which accounts for 60%–70% of all cases of dementia (Daulatzai, 2010). AD patients often have neuropathological changes in components of the brain involved in olfactory processing, along with a reduced ability to detect, discriminate, and identify odors (Ferrer et al., 2016; Murphy, 1999). In fact, olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases (Djordjevic et al., 2008; Zhang, 2016) and has a relatively high prevalence in various types of dementia, occurring in up to 100% of AD patients (Duff et al., 2002).