ABSTRACT
Since the pioneering studies of Ansari and Johnson (1975) and Waldton (1974), it has become apparent that the ability to smell is compromised in a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Down syndrome (DS), Huntington’s disease (HD), idiopathic Parkinson’s disease (PD), multiple sclerosis (MS), and the parkinsonism-dementia complex of Guam (PDC) (for reviews, see Doty, 1991, 2001; Ferreyra-Moyano and Barragan, 1989; Hawkes et al., 1999; Mesholam et al, 1998; Moberg et al., 1999; Murphy, 1999; Serby, 1987). Alterations in olfaction in such a wide range of disorders-along with the findings of olfactory dysfunction in the normal elderly, epilepsy, multi-infarct dementia (MID), schizophrenia (SZ), and brain surgery cases-raises the possibility that such olfactory anomalies simply reflect nonspecific general disruption of central nervous system (CNS) pathways. However, this is unlikely for several reasons. First, in some diseases, such as AD and PD, the olfactory deficit presents very early in the disease process, long before significant brain deterioration is evident. Second, the degree of olfactory dysfunction differs, on average, among most of these disorders. For example, AD, PD, and PDC are accompanied by marked alterations in the ability to smell, whereas HD, MID, and SZ are accompanied by more moderate alterations. Progressive supranuclear palsy (PSP) and l-methyl-4-phenyl-l, 2, 3, 6tetrahydropyridine-induced parkinsonism (MPTP-P) are associated with only minor changes in the ability to smell, in spite of the fact that they share major clinical features with PD. Third, in some neurodegenerative diseases, such as PD, scores on most olfactory tests are unrelated to disease stage or progression, whereas in others, such as AD, this appears not to be the case. And finally, it is now well established that in MS the number of plaques within olfactory-related CNS structures, but not in other brain regions, is strongly correlated with the degree of olfactory dysfunction.
