No Cognitive Impairment Group Research Articles

Quantifying neuroinflammation within deep gray matter in small vessel disease using diffusion tensor based free-water imaging: a longitudinal study

PurposeEmploying free water (FW) imaging, a cutting-edge diffusion MRI technique, we assessed neuroinflammation within deep gray matter (DGM) in small vessel disease (SVD) over 1–2 years.MethodOne hundred and seventy SVD patients and 21 healthy controls (HCs) underwent MRI scans and neuropsychological evaluations at baseline. These patients were then categorized into two groups: 67 displayed no cognitive impairment (NCI), while 103 exhibited vascular mild cognitive impairment (VaMCI). A follow-up study 1–2 years later included 23 from the NCI group and 28 from the VaMCI group. Calculation of FW values within DGM facilitated both cross-sectional and longitudinal analysis, revealing partial correlations between FW value changes and cognitive function alternations.ResultsBaseline examinations disclosed significant differences in DGM FW values among the three participant groups. We found increased mean FW values in the left pulvinar (Pul), bilateral lateral nuclei (LN) and bilateral internal medullary lamina of the thalamus in VaMCI participants compared with their NCI counterparts in longitudinal analysis. Notably, negative associations emerged between the FW value changes in the left Pul and the right LN of the thalamus and MoCA score changes in the VaMCI group over 1–2 years.ConclusionsThese findings support the hypothesis that increased FW value is present at the preclinical stage of SVD and remains persistent during the early course of the disease, potentially acting as the biomarker for the mechanism of underlying cognitive decline in SVD.

The association between cognitive ability and opioid prescribing in vulnerable older adults with chronic pain in ambulatory care: a secondary data analysis using the Medical Expenditure Panel Survey

BackgroundVulnerable older adults living with Alzheimer’s disease or Alzheimer’s disease and related dementia (AD/ADRD) and chronic pain generally receive fewer pain medications than individuals without AD/ADRD, especially in nursing homes. Little is known about pain management in older adults with AD/ADRD in the community. The aim of the study was to examine opioid prescribing patterns in individuals with chronic pain by levels of cognitive ability in ambulatory care.MethodsWe used the Medical Expenditure Panel Survey (MEPS), years 2002–2017, and identified three levels of cognitive impairment: no cognitive impairment (NCI), individuals reporting cognitive impairment (CI) without an AD/ADRD diagnosis, and individuals with a diagnosis of AD/ADRD. We examined any receipt of an opioid prescription and the number of opioid prescriptions using a logistic and negative binomial regression adjusting for sociodemographic and health characteristics and stratifying by three types of chronic pain (any chronic pain, severe chronic pain, and chronic pain identified through ICD 9/10 chronic pain diagnoses).ResultsAmong people with any chronic pain, adjusted odds of receiving an opioid for people with CI (OR 1.41, 95% confidence interval 1.31–1.52) and AD/ADRD (OR 1.23, 95% confidence interval 1.04–1.45) were higher compared to NCI. Among people with chronic pain ICD 9/10 conditions, the odds of receiving an opioid were also higher for those with CI (OR 1.43, 95% confidence interval 1.34–1.56) and AD/ADRD (OR 1.48, 95% confidence interval 1.23–1.78) compared to NCI. Among those with severe chronic pain, people with CI were more likely to receive an opioid (OR 1.17, 95% confidence interval 1.07–1.27) relative to NCI (OR 0.89, 95% confidence interval 0.75–1.06). People with AD/ADRD experiencing severe chronic pain were not more likely to receive an opioid compared to the NCI group. Adjusted predicted counts of opioid prescriptions showed more opioids in CI and AD/ADRD in all chronic pain cohorts, with the largest numbers of opioid prescriptions in the severe chronic pain and ICD 9/10 diagnoses groups.ConclusionsThe results suggest increased opioid use in people living with CI and AD/ADRD in the ambulatory care setting and potentially indicate that these individuals either require more analgesics or that opioids may be overprescribed. Further research is needed to examine pain management in this vulnerable population.

Prediction of cognitive status and 5‐year survival for elderly with diabetes by using the Neurocognitive Frailty Index (NFI)

AbstractBackgroundType 2 diabetes mellitus has been shown to be associated to cognitive decline and an increased risk of mild cognitive impairment and dementia in elderly persons (Biessels et al., 2014). The aim of this research was to determine whether the Neurocognitive Frailty Index (NFI, Pakzad et al., 2017) could help to predict cognitive changes in elderly people with diabetes.MethodParticipants in this study were drawn from waves 1 (1991 to 1992) and 2 (1996 to 1997) of the Canadian Study of Health and Aging (CSHA) for prediction of 5‐year cognitive changes in those who received a consensus diagnosis of no cognitive impairment (NCI) or cognitive impairment but not dementia (CIND) in wave 1 (n = 997). The CIND category was contained to individuals whose level of cognitive impairment was measured to be greater than the NCI group but less than the dementia group. NFI was defined as a combined score of 41 physical and mental components (in 8 cognitive domains) as they were available in the dataset (NFI has 42 components but we withdraw diabetes). Cognitive score (measured by 3MS) at follow‐up, and mortality were outcome.ResultMean NFI and standard deviation was 9.7±6.22 in people without diabetes, 11.71±5.42 in people with diabetes and 9.36±5.30 in people with diabetes but are using treatment. Multiple linear regression indicated that NFI score is significantly associated to cognitive status (3MS at follow‐up, p<0.05), however, diabetes did not show any significant association to predict this outcome. CHAID decision tree analysis stratified NFI scores into five categories, while proportional hazards analysis adjusted for age, gender and education indicated that NFI was more correlated to survival than age and had a dose‐response effect in relation to survival. Those with diabetes had a higher probability of death compared to those without (p<0.05).ConclusionNFI was significantly associated with cognitive changes for the elderly in those with and without diabetes. Given that the NFI is proving to be a valuable tool to assess the risk of developing dementia, further investigation is needed to clarify which modifiable risk factors may help reduce the risk of cognitive decline.

Frailty in Relation to Cognition in Community‐Dwelling Older Adults: Validating the Electronic Frailty Index based on the Comprehensive Geriatric Assessment (eFI‐CGA) in Primary Care

AbstractBackgroundFrailty can be screened using the Clinical Frailty Scale (CFS) and quantified using a Frailty Index (FI) based on deficit accumulation. Higher degrees of frailty have been associated with greater risks of adverse outcomes, including dementia. Comprehensive Geriatric Assessment (CGA, allows development of individualized care plans for older adults’) has been used to derive an FI‐CGA. To promote effective assessment of frailty outside specialized geriatric services, we developed and are validating an electronic CGA with an automated electronic FI‐CGA (eFI‐CGA). The goal is early detection and management of frailty in home‐living older adults. Here, we examined the characteristics and robustness of the eFI‐CGA assessed by primary‐care physicians and investigated the relationship between the eFI‐CGA and cognition.MethodData were collected as part of the collaborative effort between Fraser Health and Nova Scotia Health to validate the eFI‐CGA. Baseline assessments were conducted at primary care clinics using eFI‐CGA software tools with the eFI‐CGA created following standard procedures. Dementia diagnoses on no cognitive impairment (NCI), mild cognitive impairment (MCI), and dementia were made following DSM‐IV criteria. For robustness testing, multiple interactions of the eFI‐CGA were generated, excluding cognitive measures. Data were analyzed employing regression and descriptive statistics.ResultThe sample (n = 137; age = 79.2±7.6 years, women = 67.9%; CFS = 3.7±1.3) contained 82.5% NCI and 17.5% MCI/dementia cases. Participants with MCI/dementia were slightly older, less educated, more likely to live alone and take 7+ medications, compared to those with NCI. Sores of the various integrations of the eFI‐CGA were highly correlated. These showed consistent distributions, age relationships, and the maximum values <0.70. The NCI group showed the lowest mean eFI‐CGA scores consistently across the iterations. Close correlations of the eFI‐CGA with the CFS (p<0.001) and the mini‐cog (p<0.010) were observed.ConclusionThe characteristics of the eFI‐CGA in primary care were consistent with those widely reported for the FI. A clear association between the eFI‐CGA and cognition was found, even when cognitive measurements were excluded from the eFI‐CGA. Ongoing work will test the generalizability of these findings, with a larger sample size and follow‐up assessments and outcomes, as well as examine how primary care CGA data compared with geriatrician assessments.

Multi-Dimensional Diffusion Tensor Imaging Biomarkers for Cognitive Decline From the Preclinical Stage: A Study of Post-stroke Small Vessel Disease.

Objectives: We aim to investigate whether multi-dimensional diffusion tensor imaging (DTI) measures can sensitively identify different cognitive status of cerebral small vessel disease (CSVD) and to explore the underlying pattern of white matter disruption in CSVD.Methods: Two hundred and two participants were recruited, composed of 99 CSVD patients with mild cognitive impairment (VaMCI) and 60 with no cognitive impairment (NCI) and 43 healthy subjects as normal controls (NC). Full domain neuropsychological tests and diffusion-weighted imaging were performed on each subject. DTI metrics such as fractional anisotropy (FA), mean diffusivity (MD), the skeletonized mean diffusivity (PSMD), and structural brain network measures including network strength, global efficiency (EGlobal), and local efficiency (ELocal) were calculated. Region of interest (ROI) analysis of 42 white matter tracts was performed to examine the regional anatomical white matter disruption for each group.Results: Significant differences of multiple cognitive test scores across all cognitive domains especially processing and executive function existed among the three groups. DTI measures (FA, MD, and PSMD) showed significant group difference with the cognitive status changing. FA and EGlobal showed significant correlation with processing speed, executive function, and memory. ROI analysis found that white matter integrity impairment occurred from the preclinical stage of vascular cognitive impairment (VCI) due to CSVD. These lesions in the NCI group mainly involved some longitudinal fibers such as right superior longitudinal fasciculus (SLF-R), right superior fronto-occipital fasciculus (SFO-R), and right uncinate fasciculus (UNC-R), which might be more vulnerable to the cerebrovascular aging and disease process.Conclusions: DTI measures are sensitive neuroimaging markers in detecting the early cognitive impairment and able to differentiate the different cognitive status due to CSVD. Subtle changes of some vulnerable white matter tracts may be observed from the preclinical stage of VCI and have a local to general spreading pattern during the disease progression.

Cognitive dedifferentiation as a function of cognitive impairment in the ADNI and MemClin cohorts.

The cause of cognitive dedifferentiation has been suggested as specific to late-life abnormal cognitive decline rather than a general feature of aging. This hypothesis was tested in two large cohorts with different characteristics. Individuals (n = 2710) were identified in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) research database (n = 1282) in North America, and in the naturalistic multi-site MemClin Project database (n = 1223), the latter recruiting from 9 out of 10 memory clinics in the greater Stockholm catchment area in Sweden. Comprehensive neuropsychological testing informed diagnosis of dementia, mild cognitive impairment (MCI), or subjective cognitive impairment (SCI). Diagnosis was further collapsed into cognitive impairment (CI: MCI or dementia) vs no cognitive impairment (NCI). After matching, loadings on the first principal component were higher in the CI vs NCI group in both ADNI (53.1% versus 38.3%) and MemClin (33.3% vs 30.8%). Correlations of all paired combinations of individual tests by diagnostic group were also stronger in the CI group in both ADNI (mean inter-test r = 0.51 vs r = 0.33, p < 0.001) and MemClin (r = 0.31 vs r = 0.27, p = 0.042). Dedifferentiation was explained by cognitive impairment when controlling for age, sex, and education. This finding replicated across two separate, large cohorts of older individuals. Knowledge that the structure of human cognition becomes less diversified and more dependent on general intelligence as a function of cognitive impairment should inform clinical assessment and care for these patients as their neurodegeneration progresses.

Cognition in chronic kidney disease patients: Evaluation with the Beijing version of the Montreal Cognitive Assessment

Patients with chronic kidney disease (CKD) may undergo cognitive impairment. We aimed to explore the cognition of patients with cognitive impairment (CI) and no cognitive impairment (NCI) respectively and the effect of demographics, estimated glomerular filtration rate (eGFR), number of comorbidities (NCD), and hemoglobin on CI in Chinese patients with CKD at stage 3–5 treated by nondialysis by using the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ). A total of 120 patients with CKD were recruited from the Department of Nephrology at the Affiliated Hospital of Nanjing University of Chinese Medicine at in-patient and out-patient follow up. A logistic regression model was performed to assess the effect of these variables on CI of CKD patients. The results indicated that the CI group was mainly in the decline of visuospatial and executive function, abstraction, and memory, compared with the NCI group. In addition, years of education, eGFR and NCD were found as predictors of CI of CKD patients at stage 3–5. Specifically, lower eGFR, less years of education and more comorbidities were risk predictors of CI.

Deep microbleeds and periventricular white matter disintegrity are independent predictors of attention/executive dysfunction in non-dementia patients with small vessel disease.

Cerebral small vessel disease (SVD) is the common cause of cognitive decline in the old population. MRI can be used to clarify its mechanisms. However, the surrogate markers of MRI for early cognitive impairment in SVD remain uncertain to date. We investigated the cognitive impacts of cerebral microbleeds (CMBs), diffusion tensor imaging (DTI), and brain volumetric measurements in a cohort of post-stroke non-dementia SVD patients. Fifty five non-dementia SVD patients were consecutively recruited and categorized into two groups as no cognitive impairment (NCI) (n = 23) or vascular mild cognitive impairment (VaMCI) (n = 32). Detailed neuropsychological assessment and multimodal MRI were completed. The two groups differed significantly on Z scores of all cognitive domains (all p < 0.01) except for the language. There were more patients with hypertension (p = 0.038) or depression (p = 0.019) in the VaMCI than those in the NCI group. Multiple regression analysis of cognition showed periventricular mean diffusivity (MD) (β = -0.457, p < 0.01) and deep CMBs numbers (β = -0.352, p < 0.01) as the predictors of attention/executive function, which explained 45.2% of the total variance. Periventricular MD was the independent predictor for either memory (β = -0.314, p < 0.05) or visuo-spatial function (β = -0.375, p < 0.01); however, only small proportion of variance could be accounted for (9.8% and 12.4%, respectively). Language was not found to be correlated with any of the MRI parameters. No correlation was found between brain atrophic indices and any of the cognitive measures. Arteriosclerotic CMBs and periventricular white matter disintegrity seem to be independent MRI surrogated markers in the early stage of cognitive impairment in SVD.

Trajectories of Depressive Symptomatology in Rural Memory Clinic Patients between Baseline Diagnosis and 1-Year Follow-Up

Background/Aims: To investigate the prevalence and trajectories of depressive symptomatology at 1-year follow-up, and the severity of depressive symptoms, by dementia diagnostic group, as well as to determine the predictors of depressive symptomatology at 1-year follow-up. Methods: In rural and remote patients of an interdisciplinary memory clinic between 2004 and 2014, 144 patients diagnosed with no cognitive impairment (NCI), mild cognitive impairment, dementia due to Alzheimer's disease (AD), or non-AD dementia completed the Center for Epidemiologic Studies of Depression Scale to assess depressive symptomatology at both time points. Results: Among patients with data at both time points, persistence of depressive symptomatology at follow-up occurred in 22.2%, remission in 17.4%, incidence in 13.2%, and absence in 47.2%. The prevalence of depressive symptomatology at baseline and persistence at follow-up were significantly greater in the NCI group than in the other diagnostic groups, but there were no differences in severity. Depressive symptomatology at follow-up was independently associated with depressive symptomatology, lower independence in activities of daily living, and lower self-rating of memory at baseline, as well as with decreased independence in activities of daily living between time points. Conclusion: Future studies should further examine short-term postdiagnostic trajectories in depressive symptomatology in multiple dementia diagnostic groups to inform prognoses and treatment decisions.

Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer's Disease

Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism.

The determinants and longitudinal course of post-stroke mild cognitive impairment

While post-stroke dementia has been extensively investigated, the large number of patients with mild cognitive impairment (MCI) following stroke has received less attention, and reports on the longitudinal course of such impairment are inconsistent in their findings. We examined patients with MCI (n = 45) or no cognitive impairment (NCI) (n = 59), based on consensus criteria following detailed neuropsychological assessments and magnetic resonance imaging (MRI) scans, and compared them with healthy control subjects (n = 84), all of whom were assessed at two time points, 3 years apart. The MCI at baseline in this group was judged to be vascular in etiology (vaMCI). Incident dementia was diagnosed in 24.4% of vaMCI and 8.5% of NCI subjects and no control subjects over 3 years, giving a rate of conversion of approximately 8% per year in post-stroke vaMCI. The vaMCI group showed greater decline in logical memory than the NCI group. Within the vaMCI group, those who developed dementia had great decline in language and executive function. Compared with NCI patients, those with vaMCI had more vascular risk factors and more white matter hyperintensities on MRI at baseline, but did not differ in their brain or hippocampal volumes. Neither MRI volumetric measures nor interval cerebrovascular events predicted decline in function. The major determinant of decline and categorical transition was impaired performance at baseline, suggesting that those with mild impairment post-stroke are more vulnerable to subsequent decline.

Effects of demographic factors on cortical thickness in Alzheimer's disease

The aim of this study was to investigate the effect of demographic factors (age of onset, sex and years of education) on the distribution of cortical thickness in a large sample of patients with Alzheimer's disease (AD). The study participants consisted of 193 AD patients and 142 controls with no cognitive impairment (NCI) that were measured with cortical thickness across the entire brain. The effects of demographic factors on cortical thickness were analyzed by applying linear regression after controlling confounding factors. Older individuals in NCI group showed more cortical thinning in frontal, temporal association cortices and insula than younger participants. Early onset AD was associated with cortical thinning in the parietal lobe, whereas late onset AD was associated with cortical thinning in the medial temporal region. The NCI group demonstrated sex-related differences in cortical thickness, although those differences were not present in the AD group. While the education effect was absent in NCI individuals, high levels of education in the AD group correlated with cortical thinning in the frontal and temporoparietal association cortices. Our results show that AD with earlier onset and higher education had suffered more pronounced cortical atrophy in specific parts of the brain than their counterparts, which may be related to cognitive reserve theory.

Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment

To evaluate the total number of synapses in the stratum radiatum (str rad) of the human hippocampal CA1 subfield in individuals with mild Alzheimer disease (mAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI) and determine if synapse loss is an early event in the progression of the disease. Short postmortem autopsy tissue was obtained, and an unbiased stereologic sampling scheme coupled with transmission electron microscopy was used to directly visualize synaptic contacts. Individuals with mAD had fewer synapses (55%) than the other two diagnostic groups. Individuals with MCI had a mean synaptic value that was 18% lower than the NCI group mean. The total number of synapses showed a correlation with several cognitive tests including those involving both immediate and delayed recall. Total synaptic numbers showed no relationship to the subject's Braak stage or to APOE genotype. The volume of the str rad was reduced in mAD vs the other two diagnostic groups that were not different from each other. These results strongly support the concept that synapse loss is a structural correlate involved very early in cognitive decline in mild Alzheimer disease (mAD) and supports mild cognitive impairment as a transitional stage between mAD and no cognitive impairment.

The Significance of Pin1 in the Development of Alzheimer's Disease

Pin1 protein, a peptidyl-prolyl cis-trans isomerase plays an important regulatory role in neuronal function. Recent studies indicate that Pin1 may promote the dephosphorylation of tau and restore its ability to bind to and polymerize microtubles. Previous studies on postmortem human brains showed that Pin1 is down-regulated in advanced Alzheimer's disease (AD) brains compared to age-matched non-demented controls. Because AD is a slowly progressive disease with a preclinical period that can last years, the abundance and regulatory function of Pin1 may vary on the course of the disease. In order to evaluate the potential contribution of Pin1 to AD pathogenesis, levels of mRNA, protein and isomerase activity of Pin1 and phosphorylated tau from postmortem brains of 10 persons with mild-cognitive impairment (MCI), 10 with AD and 10 age-matched no cognitive impairment (NCI) were measured. The relationship between Pin1 and phosphorylated tau as well as clinical and cognitive data were analyzed. The results indicated that Pin1 activity in MCI and AD were significantly higher than in NCI. Phosphorylated tau in MCI and AD was also higher than in NCI group. The positive correlation trend in MCI and the robust correlation in AD between Pin1 activity and phosphorylated tau implies that increasing phosphorylated tau during AD pathogenesis may induce the compensatory activation/up-regulation of Pin1, while the inverse correlation between Pin1 activity and phosphorylated tau in NCI group implies that decreased Pin1 may play a role in the initial accumulation of phosphorylated tau in AD pathogenesis.

Preclinical Vascular Cognitive Impairment and Alzheimer Disease

Neuropsychological changes that precede a diagnosis of vascular cognitive impairment (VCI) and the differences between preclinical VCI and Alzheimer disease (AD) are not well understood. We compared the neuropsychological performances of people with incident VCI, incident AD, and no cognitive impairment (NCI) 5 years before their clinical diagnoses. The Canadian Study of Health and Aging is a prospective, cohort study of 10,263 randomly selected persons age 65 years or older. We studied 332 individuals who had completed a battery of neuropsychological tests and were diagnosed with NCI at baseline. After 5 years, 41 were diagnosed with VCI, 25 with AD, and 266 with NCI. At baseline, the incident-VCI group performed worse on a wide range of neuropsychological tests compared with the NCI group. A test of abstract reasoning was selectively low in the incident-VCI group, relative to both the incident-AD and NCI groups. The incident-AD group performed worse at baseline on memory tests compared with incident-VCI and NCI groups. This study suggests a preclinical phase may exist in VCI that differs from that in AD. Neuropsychological measures may aid the design of preventive strategies for VCI.

Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment

One of the major neuropathological findings in the brains of individuals with Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and hippocampus. Here we report, for the first time, an estimate of the total number of synapses in the outer molecular layer (OML) of the human dentate gyrus, in individuals with early Alzheimer's disease (eAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme coupled with transmission electron microscopy to directly visualize synaptic contacts, was used to estimate the total number of synapses in short postmortem autopsy tissue. Individuals with eAD had significantly fewer synapses than the other two diagnostic groups. Seventy-five percent of the individuals with MCI had synaptic values that were lower than the NCI group mean. The number of synapses showed a significant correlation with the subject's Mini-Mental State score and with cognitive tests involving delayed recall. Synaptic loss showed no relationship to Braak stage or to apoE genotype. The volume of the OML was significantly reduced in eAD compared to the other two diagnositic groups that were not different from each other. These data suggest that a loss of afferents from the entorhinal cortex underlie the synapse loss seen in eAD. This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline.

Five-Year Outcomes for Dementia Defined Solely by Neuropsychological Test Performance

Cognitive impairment that does not meet criteria for dementia is common and progresses to dementia at a high rate. It is not clear how best to define this type of cognitive impairment. We assessed the predictive validity of different case definitions for cognitive impairment and dementia by comparing rates of adverse outcomes for individuals who did not meet dementia criteria but had neuropsychological test results indicating dementia (NPDementia), those who had traditional dementia diagnoses (mild and moderate-severe severity), those who had other cognitive impairment but no dementia (CIND), and those with no cognitive impairment (NCI). Our sample comprised 1,659 participants who had completed a neuropsychological assessment in the Canadian Study of Health and Aging, a prospective, cohort study of 10,263 randomly selected persons aged 65 years or older. Outcomes were determined after 5 years. Institutionalization and death rates for the NPDementia and CIND groups were higher than for the NCI group. Both groups had lower institutionalization rates than the two Dementia groups and lower death rates than the Moderate-Severe Dementia group. Rates of progression to dementia were increased in NPDementia and CIND groups, relative to the NCI group, and the NPDementia group was less likely than the CIND group to revert to a diagnosis of NCI at the 5-year follow-up. Thus, individuals with NPDementia and CIND have substantially worse outcomes over 5 years than those with NCI. The case definition of NPDementia identified individuals with cognitive impairment that is unlikely to resolve and likely to progress to dementia.