Cognitive Decline In Neurodegenerative Diseases Research Articles

Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume. Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model

BackgroundNew strategies are urgently needed to manage and delay the development of Alzheimer’s disease (AD). Neuroinflammation is a significant contributor to cognitive decline in neurodegenerative diseases, including AD. Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) protect hypertensive patients against AD, but the cellular and molecular mechanisms underlying these effects remain unknown. In light of this, the protective effects of three ARBs and three ACEIs against neuroinflammation and cognitive decline were investigated through comprehensive pharmacologicalin vitro/in vivoscreening. MethodsBV-2 microglia cells were exposed tolipopolysaccharide (LPS) and treated with ARBs and ACEIs to provide initial insights into the anti-inflammatory properties of the drugs. Subsequently, irbesartan was selected, and its efficacy was evaluated inC57/BL6 male miceintranasally administered with irbesartan and injected with LPS. Long-term memory and depressive-like behavior were evaluated; dendritic spines were measured as well as neuroinflammation, neurodegeneration and cognitive decline biomarkers. ResultsIrbesartan mitigated memory loss and depressive-like behavior in mice treated with LPS, probably because itincreased spine density, ameliorated synapsis dysfunction and activated the PI3K/AKT pathway. Irbesartan elevated the levels of hippocampalsuperoxide dismutase2 andglutathione peroxidaseandsuppressed LPS-induced astrogliosis. ConclusionsOverall, this study provides compelling evidence that multiple intranasal administrations of irbesartan can effectively prevent LPS-induced cognitive decline by activating pathways involved in neuroprotection and anti-inflammatory events. These findings underscore the potential of irbesartan as a preventive strategy against the development of AD and other neurodegenerative conditions associated with neuroinflammation.

Studying lack of awareness of cognitive decline in neurodegenerative diseases requires measures of both anosognosia and denial.

The cause(s) of lack of awareness of cognitive decline in neurodegenerative diseases can be multifactorial. Yet neurologically oriented research on anosognosia of cognitive decline almost exclusively assumes that the underlying disturbance of neuro-networks that support various cognitive functions accounts for the reduced self-awareness. Cultural and psychosocial factors, including the person's emotional state, however, can contribute to the underreporting or avoidance of admitting to cognitive impairments in neurodegenerative diseases. Research on the causes of lack of awareness of cognitive decline in neurodegenerative disorders needs to include these variables. We briefly present two case examples of underreporting or "unawareness" of memory difficulties in persons with mild cognitive impairment (MCI) (or minor neurocognitive disorder). One presented with classic anosognosia for memory impairment, while the other initially reported no memory impairment but later admitted to "denying" her memory difficulties secondary to anxiety. Based on these patients' clinical presentations and available research, we suggest three potential screening items that may help identify probable denial of memory impairments when studying anosognosia in MCI.

The sodium glucose co-transporter 2 inhibitor ertugliflozin for Alzheimer's disease: Inhibition of brain insulin signaling disruption-induced tau hyperphosphorylation

An antidiabetic agent sodium glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin has been revealed to bind to catalytic anionic site of acetylcholinesterase (AChE), which is considered to be associated with the cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD). The aim of the present study was thus to probe the effect of ertugliflozin on AD. Intracerebroventricular injection of streptozotocin (STZ/i.c.v) (3 mg/kg) was done bilaterally in male Wistar rats at 7–8 weeks of age. Two treatment doses (5 mg/kg and 10 mg/kg) of ertugliflozin were given intragastrically to STZ/i.c.v-induced rats for 20 days daily for behavioral assessment. Biochemical estimations of cholinergic activity, neuronal apoptosis, mitochondrial function and synaptic plasticity were performed. Behavioral results with ertugliflozin treatment revealed attenuation of cognitive deficit. Ertugliflozin also inhibited hippocampal AChE activity, downregulated pro-apoptotic marker expression, as well as mitigated mitochondrial dysfunction and synaptic damage in STZ/i.c.v rats. Importantly, we found that the hyperphosphorylation of tau in the hippocampus of STZ/i.c.v rats was decreased after oral administration of ertugliflozin, which was accompanied by decreased Phospho.IRS-1Ser307/Total.IRS-1 ratio and increased Phospho.AktSer473/Total.Akt and Phospho.GSK3βSer9/Total.GSK3β ratios. Our results indicated that treatment with ertugliflozin reversed AD pathology, which may be associated with inhibition of insulin signaling disruption-induced tau hyperphosphorylation.

A novel antibody‐free mass spectrometry panel of CSF biomarkers for synaptic dysfunction

AbstractBackgroundOne of the earliest events and the best correlate to cognitive decline in neurodegenerative diseases, such as Alzheimer’s disease (AD), is synaptic dysfunction and degeneration. Thus, identifying and validating new biomarkers capable of quantifying synaptic degeneration for use as prognostic biomarkers would be very valuable for diagnostic purposes. We have developed a novel assay in which 17 synaptic proteins are simultaneously quantified in cerebrospinal fluid (CSF). The proteins in the panel include but are not limited to: synucleins, neuronal pentraxins, SNARE proteins and neurogranin. In a pilot study, we previously observed that several of these proteins may serve as synaptic biomarkers for AD. In this follow‐up study we aimed to confirm our previous results as well as expand to other neurodegenerative disease such as frontotemporal lobar degeneration (FTLD) and disorders with α‐synuclein pathology.MethodSample preparation of 100 µL CSF samples was performed in a consecutive three‐step process constituting of stable isotope labeled peptide standards addition, tryptic digestion followed by purification by solid‐phase extraction. For quantification was micro‐high‐performance liquid chromatography‐mass‐spectrometry (triple quadrupole) used. A cross‐sectional study including controls (n=47), AD (n=63), FTLD (n=103) and α‐synuclein patients (n=22) was performed.ResultIn the study the most notable results were found for 14‐3‐3 zeta/delta, beta‐synuclein and the pentraxins. All three pentraxins (1, 2 and the receptor) were decreased compared to controls across all groups, while 14‐3‐3 zeta/delta was increased. Further, beta‐synuclein was seemingly specifically altered (increased) between controls and AD, while no difference was observed between controls and FTLD, and α‐synuclein patients.ConclusionWe have successfully developed a panel of novel CSF biomarkers for synaptic dysfunction. We present results suggesting that several synaptic proteins potentially could be used as biomarkers for synaptic dysfunction and degeneration in not only AD but also other neurodegenerative diseases such as FTLD and α‐synuclein pathologies.

MeCP2 prevents age-associated cognitive decline via restoring synaptic plasticity in a senescence-accelerated mouse model.

Age‐related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl‐CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence‐accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated‐resistant 1 (SAMR1) mice. MeCP2‐mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age‐related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age‐related cognitive decline in neurodegenerative diseases.

Towards cross‐cohort estimation of cognitive decline in neurodegenerative diseases

AbstractBackgroundHeterogeneity of cohorts, in terms of inclusion criteria, design of follow‐up visits and batteries of cognitive assessments, hinders any thorough comparisons between them. For that reason, we build a cross‐cohort model of cognitive decline that can be personalized to any patient, allowing to impute partially or totally missing scores. This enables to compare the subjects’ progression across cohorts thanks to common cognitive assessments.MethodBased on a generic framework of disease progression that handles longitudinal data (Schiratti et al. 2015, NIPS) and implemented in the Leaspy Python package, we first estimate the joint progression of a large set of cognitive scores from the ADNI database along a common disease timeline. This group‐average progression is then personalized to individual trajectories of patients from the PharmaCog and AIBL cohorts. In particular, all individuals are characterized by a relative pace of progression and onset age that can be compared across cohorts. To validate our model, we impute missing values of a given score, based on its past and future values together with the dynamics of concurrent scores and compare errors to constant predictions and linear regressions. We finally go further by simulating purposely concealed scores thanks to the progression of the remaining features so to mock reconstruction of scores that are entirely missing in a particular cohort.ResultsFigure 1 shows the relative positioning of all subjects from the 3 cohorts based on their individual pace of progression and their age at disease onset. Such characterization enables to impute missing values of the MMSE or the Immediate/Delayed Logical Memory better than imputing the last known value or fitting a linear regression [Figure 2]. Furthermore, from the multiple measurements of a single score, the model is able to reconstruct the individual progression of the other scores at the corresponding visits [Figure 3], with a controlled error rate.ConclusionOur model enables comparison of patients trajectories from different cohorts. It permits to lessen imputation errors of most cognitive scores in new cohorts and demonstrates a new way to simulate, at any individual visit, scores that have not been measured in practice.

Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Against Cognitive Decline in Neurodegenerative Diseases.

Cognitive impairment is one of the major symptoms in most neurodegenerative disorders such as Alzheimer’s (AD), Parkinson (PD), and Huntington diseases (HD), affecting millions of people worldwide. Unfortunately, there is no treatment to cure or prevent the progression of those diseases. Cognitive impairment has been related to neuronal cell death and/or synaptic plasticity alteration in important brain regions, such as the cerebral cortex, substantia nigra, striatum, and hippocampus. Therefore, compounds that can act to protect the neuronal loss and/or to reestablish the synaptic activity are needed to prevent cognitive decline in neurodegenerative diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two highly related multifunctional neuropeptides widely distributed in the central nervous system (CNS). PACAP and VIP exert their action through two common receptors, VPAC1 and VPAC2, while PACAP has an additional specific receptor, PAC1. In this review article, we first presented evidence showing the therapeutic potential of PACAP and VIP to fight the cognitive decline observed in models of AD, PD, and HD. We also reviewed the main transduction pathways activated by PACAP and VIP receptors to reduce cognitive dysfunction. Furthermore, we identified the therapeutic targets of PACAP and VIP, and finally, we evaluated different novel synthetic PACAP and VIP analogs as promising pharmacological tools.

Benzothiazole amphiphiles promote RasGRF1‐associated dendritic spine formation in human stem cell‐derived neurons

Synaptic dysfunction has been implicated as an early cause of cognitive decline in neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD). Methods to slow down or reverse the loss of functional synapses, therefore, represent a promising avenue to explore for treating NDDs. We have previously reported the development of a class of benzothiazole amphiphiles (BAMs) that exhibited the capability to improve memory and learning both in wild‐type mice and in an AD rodent model, putatively through promoting RasGRF1‐associated formation of dendritic spines in hippocampal neurons. While these results represent a good first step in exploring a new approach to treating NDDs, the capability of these compounds to increase spine density has not been previously examined in a human neuronal model. Here, we found that neurons derived from differentiated human induced pluripotent stem cells exhibited both an increase in RasGRF1 expression and a phenotypic increase in the density of postsynaptic density protein 95‐positive puncta (which we use to provide an estimate of dendritic spine density) in BAM‐treated vs. control neurons. These results demonstrate that the previously observed spinogenic effects of BAMs in rodent neurons can be recapitulated in a human neuronal model, which further supports the potential utility of BAM agents for treating human diseases associated with spine deficits such as AD or other NDDs.

Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro.

Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson’s disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder.

An analog derived from phenylpropanoids ameliorates Alzheimer's disease–like pathology and protects mitochondrial function

The abnormal proliferation and neurogenesis of neural progenitor cells (NPCs) is usually associated with the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). Mitochondrial stress is one of the most prominent features of AD and is thought to be involved in the impairment of the neurogenesis and proliferation of NPCs. Thus, restoring mitochondrial function by pharmaceutical intervention may alleviate disease-related defects in neurogenesis and is considered a potential therapeutic strategy for AD. In the present study, we found that the oral administration of PL201A, a designed analog of phenylpropanoids, which are a family of natural products with antiaging effects, promoted the neurogenesis and proliferation of NPCs and ameliorated cognitive impairment in a transgenic mouse model of AD. Furthermore, PL201A attenuated amyloid-β–induced mitochondrial stress and promoted NPC proliferation in vitro. Further mechanistic studies showed that PL201A restored the activation of AMP-regulated protein kinase–retinoblastoma signaling, which was suppressed by amyloid-β. Our findings suggest that PL201A may represent a promising regenerative therapeutic agent for cognitive decline in neurodegenerative diseases.

Clinical practice guidelines for the management of olfactory dysfunction — Secondary publication

ObjectiveTo provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society. MethodsSeven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were “smell disorder,” “olfactory dysfunction,” “olfactory loss,” “olfactory disturbance,” “olfactory impairments,” “olfaction disorder,” “smell disorder,” “anosmia,” “cacosmia,” and “dysosmia.” Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A—strongly recommended to D—not recommended, were adopted for the management of olfactory dysfunction. ResultsBoth oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases. ConclusionThe Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction.

Proteomics for synaptic markers of cognitive decline in neurodegenerative diseases.

Proteomics for synaptic markers of cognitive decline in neurodegenerative diseases.

Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach.

See Attems and Jellinger (doi:10.1093/brain/awx360) for a scientific commentary on this article.Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups. Significant loss of SNAP47, GAP43, SYBU (syntabulin), LRFN2, SV2C, SYT2 (synaptotagmin 2), GRIA3 and GRIA4 were further validated on a larger cohort comprised of 92 brain samples using ELISA or western blot. Cognitive impairment before death and rate of cognitive decline significantly correlated with loss of SNAP47, SYBU, LRFN2, SV2C and GRIA3 proteins. Besides differentiating Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease from controls with high sensitivity and specificity, synaptic proteins also reliably discriminated Parkinson's disease dementia from Alzheimer's disease patients. Our results suggest that these particular synaptic proteins have an important predictive and discriminative molecular fingerprint in neurodegenerative diseases and could be a potential target for early disease intervention.

Inhibition of 12/15 LOX ameliorates cognitive and cholinergic dysfunction in mouse model of hypobaric hypoxia via. attenuation of oxidative/nitrosative stress

12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia-induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX. Hypobaric hypoxia-exposed mice had consistently increased expression of 12/15LOX and elevated 12(S) HETE levels in the hippocampus as well as plasma which were significantly mitigated following baicalein treatment. 12/15LOX inhibition also reduced hypobaric hypoxia-mediated upregulation of hippocampal HIF-1α protein expression along with reduction in expression of inflammatory genes. The inhibition of 12/15 LOX resulted in a significant decrease in NO levels in the hippocampal homogenate associated with downregulated iNOS, nNOS transcription but not eNOS speculating that 12/15 LOX is critically involved in HIF-1α, mediated by nitric oxide-induced neurotoxicity. We also observed a similar effect of 12/15 LOX inhibition on hippocampal COX2 expression. 12/15LOX inhibition could effectively modulate central cholinergic indices during hypobaric hypoxia by restoring mAChR-1, α7NAChR expression and AChE, ChAT activity in the hippocampus comparable to normal mice. We report here the mechanistic involvement of 12/15LOX in orchestrating hypoxia-associated neuronal damage and HIF-1α-dependent neuroinflammation resulting in cognitive decline.

Cognitive and cortical thinning patterns of subjective cognitive decline in patients with and without Parkinson's disease

Subjective cognitive decline (SCD) has gained attention as a predictor of future cognitive decline in neurodegenerative diseases. Based on the hypothesis that different pathologies may distinctly contribute to SCD, we investigated the cognitive profiles and cortical thickness of patients with SCD, with and without Parkinson's disease (PD). In total, 96 patients experiencing SCD were classified as having PD (SCD-PD(+), n = 49) or no neurological disease (SCD-PD(-), n = 47); cognitively normal subjects without SCD (n = 23) were included as controls. Neurocognitive profiles and cortical thickness were examined using standardized neuropsychological tests and magnetic resonance imaging-based analysis. No significant differences in demographic characteristics were found among the three groups. Neuropsychological tests demonstrated that the SCD-PD(+) patients had lower semantic fluency than SCD-PD(-) patients and controls, and showed poorer performance in visual memory and confrontational naming than controls, whereas no significant difference in cognitive performance was observed between the SCD-PD(-) patients and controls. Cortical thickness analysis revealed that the SCD-PD(+) patients had focal cortical thinning in the dorsolateral prefrontal, orbitofrontal, parietal, and parahippocampal areas compared with controls. Compared with SCD-PD(-) patients, SCD-PD(+) patients had cortical thinning in the frontal, parahippocampal, and posterior cortical areas. Our data show that cortical thinning and cognitive performance in patients with SCD may differ based on the presence of PD, suggesting that SCD in patients with PD reflects disease-related cortical thinning and cognitive dysfunctions more closely than SCD without PD.

Physical exercise-induced adult neurogenesis: a good strategy to prevent cognitive decline in neurodegenerative diseases?

Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain.

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the...

Longitudinal analysis of olfactory deficits in HIV infection

The presence and degree of odor identification deficits in 55 HIV-infected (30 asymptomatic, 25 symptomatic) and 29 HIV-negative at-risk control volunteers were examined longitudinally using the University of Pennsylvania Smell Identification Test (UPSIT). Factors other than HIV infection that could account for olfactory loss (i.e., sinusitis or upper respiratory infection) were also considered by obtaining MRI scans of the nasal passages and information from an olfaction questionnaire. No differences were found among groups at the first administration of the UPSIT, with significant differences among groups emerging at the 1-year and 2-year follow-ups. The symptomatic group showed a significant decline in odor identification scores across time, while means for the asymptomatic and control groups remained stable. The presence of sinusitis or an upper respiratory infection appeared to have no effect on odor identification. The implications for these findings in relationship to cognitive decline in neurodegenerative diseases are discussed.

Longitudinal analysis of olfactory deficits in HIV infection

The presence and degree of odor identification deficits in 55 HIV-infected (30 asymptomatic, 25 symptomatic) and 29 HIV-negative at-risk control volunteers were examined longitudinally using the University of Pennsylvania Smell Identification Test (UPSIT). Factors other than HIV infection that could account for olfactory loss (i.e., sinusitis or upper respiratory infection) were also considered by obtaining MRI scans of the nasal passages and information from an olfaction questionnaire. No differences were found among groups at the first administration of the UPSIT, with significant differences among groups emerging at the 1-year and 2-year follow-ups. The symptomatic group showed a significant decline in odor identification scores across time, while means for the asymptomatic and control groups remained stable. The presence of sinusitis or an upper respiratory infection appeared to have no effect on odor identification. The implications for these findings in relationship to cognitive decline in neurodegenerative diseases are discussed.