The methods of the Cache County Study of Memory in Aging are reported in detail elsewhere
+(17). The sampling method of this study is outlined in
+Figure 1. Briefly, we approached all permanent residents of Cache County, Utah, who were 65 years old or older in January 1995 (N=5,677). We enrolled 5,092 of these individuals (90%), who were then given the Modified Mini-Mental State
+(18). Individuals who could not participate directly were characterized by the results of an interview with the Informant Questionnaire on Cognitive Decline in the Elderly
+(19) conducted with a knowledgeable informant. Individuals whose screening scores suggested possible cognitive impairment were studied further with the Dementia Questionnaire
+(20). The Dementia Questionnaire was also used to study a stratified probability sample of the entire population (the subsample in
+Figure 1), irrespective of results on the Modified Mini-Mental State or the Informant Questionnaire on Cognitive Decline in the Elderly. The subsample, and all other participants with a Dementia Questionnaire rating of 4 (suspected dementia) or 5 (probable dementia), underwent a comprehensive clinical assessment in the presence of a collateral informant at their place of residence (including nursing homes).
The study was approved by the institutional review boards of Duke University Medical Center, the Johns Hopkins School of Public Health, and Utah State University. All study participants or their next of kin signed an informed consent document for each stage of assessment.
+
Participant Assessment, Diagnosis, and Staging of Dementia
A research nurse and a psychometric technician conducted the comprehensive evaluations, along with a board-certified geriatric psychiatrist (D.C.S. or J.C.S.B.). The geriatric psychiatrist directly evaluated 236 participants. Evaluations included history, mental status examination, standardized neurological examination, brief physical examination, and a 1-hour neuropsychological battery. In addition, we reviewed medical records when relevant and requested laboratory tests for participants with dementia, including CBC, chemistries, B12, folic acid, thyroid function tests, and urinalysis, when these tests had not been conducted in the last 6 months. Brain magnetic resonance images or, rarely and only when indicated, computerized tomography scans were also obtained for the majority of participants with dementia. Results of laboratory studies and brain imaging were used in final diagnostic formulations.
We used data from these evaluations to classify study participants into groups of participants who were evidently suffering from dementia or not and into distinct clinical diagnostic categories. These assignments were made at initial diagnostic conferences that included the staff who conducted the evaluation and a board-certified geriatric psychiatrist (D.C.S. or J.C.S.B.). Cases of participants with an initial diagnosis of dementia were then reviewed for final diagnosis at a conference that included the two geriatric psychiatrists, a board-certified neurologist, a senior neuropsychologist, and a cognitive neuroscientist.
Of 1,033 participants examined, 335 (32%) were diagnosed with dementia. Of these, 329 were rated on the Neuropsychiatric Inventory, along with 673 participants without dementia—the rest refused or could not be rated. The 329 participants with dementia who were rated on the Neuropsychiatric Inventory were further classified at the adjudication conference as to their type of dementia. On the basis of the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, 214 were diagnosed with probable or possible Alzheimer’s disease. According to Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria, 62 were diagnosed with probable or possible vascular dementia. An additional 53 received a DSM-IV diagnosis of dementia but did not meet the criteria for Alzheimer’s disease or vascular dementia; 32 of these participants were diagnosed with dementia of unknown etiology, four with frontotemporal dementia, four with hypoperfusion dementia, four with Lewy body dementia, three with alcohol-related dementia, and two each with posttraumatic dementia, normal-pressure hydrocephalus, or Pick’s disease.
Study participants with dementia were also classified by stage or severity of dementia by using the Clinical Dementia Rating
+(21), a broadly used method for rating stages of dementia. Of the 329 participants with dementia who were rated on the Neuropsychiatric Inventory, 134 were at Clinical Dementia Rating stages 0.5 or 1, 90 were at stage 2, and 105 were at stages 3–5.
+
Assessment of Mental and Behavioral Disturbances
The 1,002 participants with and without dementia were given the Neuropsychiatric Inventory by a trained psychometrician or nurse. The Neuropsychiatric Inventory is a fully structured informant interview that specifies verbatim the questions asked. Study participants were rated as experiencing or not experiencing each of 10 domains in the past month: delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, and aberrant motor behavior (e.g., wandering or pacing). Within each domain, the Neuropsychiatric Inventory includes a screening question. The rater is instructed to move to the next domain if the screening item is answered in the negative. Otherwise, the rater asks a series of individual questions describing behavior reflective of disturbance in that domain. Once the disturbances relevant to each domain (e.g., delusions) are defined for the informant, then the informant is asked about the frequency of these on a 4-point scale from 1 (occasionally) to 4 (very frequently, more than once a day). The informant is also asked to rate the severity of the behavior on a 3-point severity scale (mild, moderate, or severe).
Within each Neuropsychiatric Inventory domain, scores of 0 to 4 are possible for the frequency of the disturbance and 0 to 3 for its severity. The Neuropsychiatric Inventory then yields a domain rating of frequency times severity (range=0–12). Finally, there is a total Neuropsychiatric Inventory score that sums the individual domain scores.
Our first goal was to estimate the prevalence and severity of mental and behavioral disturbances in participants with dementia and compare these with results from nondemented participants. We compared the proportion of participants with and without dementia who had a score of 1 or higher in any individual Neuropsychiatric Inventory domain. (A score of 1 or higher indicates the presence of any disturbance in the domain.) We also compared Neuropsychiatric Inventory mean scores for participants with and without dementia as an indicator of global severity in each domain.
To test the hypothesis that participants with dementia would experience more Neuropsychiatric Inventory disturbances, we constructed a series of logistic regression models, one for each Neuropsychiatric Inventory domain and one for the Neuropsychiatric Inventory as a whole. In these models, the presence or absence of a nonzero score within a given domain (or on the Neuropsychiatric Inventory as a whole) was the dependent variable and the presence or absence of dementia was the independent variable.
To test the hypothesis that participants with dementia had higher Neuropsychiatric Inventory domain or total scores, we constructed a series of linear regression models, one for each domain and one for the total Neuropsychiatric Inventory score. Individual Neuropsychiatric Inventory domain scores or the Neuropsychiatric Inventory total score were the dependent variables, and the presence or absence of dementia was again the independent variable.
Our other goal was to compare the prevalence of mental and behavioral disturbances in participants with different types of dementia, especially Alzheimer’s disease and vascular dementia (the group with other dementias was relatively small [N=53] and heterogeneous). As before, we used logistic regression to compare the prevalence of individual disturbances and linear regression to compare Neuropsychiatric Inventory domain and total scores.
Our final goal was to assess the prevalence and severity of dementia-associated mental and behavioral disturbances across the different stages of dementia. For this purpose we calculated the prevalence of different disturbances and the mean Neuropsychiatric Inventory domain (and total) scores for participants with dementia having different Clinical Dementia Rating ratings (those with ratings of 0.5 or 1, those with ratings of 2, and those with ratings of 3–5). We used logistic regression to compare the prevalence of individual disturbances across the groups with different Clinical Dementia Rating stages, and we used analysis of variance (ANOVA) to compare Neuropsychiatric Inventory domain and total scores across the three Clinical Dementia Rating stages.
There was a small amount of missing Neuropsychiatric Inventory data (less than 5%). We note in the tables the number of participants for whom data were available for each domain of the Neuropsychiatric Inventory.
+Table 1 shows the demographic characteristics of participants with and without dementia. The participants with dementia were older and less educated, and more of them were women.
+Table 2 compares participants with and without dementia. Among those with dementia, 201 (61%) suffered from at least one Neuropsychiatric Inventory disturbance, and 105 (32%) scored at least 6 total points on the Neuropsychiatric Inventory, indicating a moderate to severe disturbance. The mean Neuropsychiatric Inventory score for participants with dementia was about 7, almost 10 times higher than the comparable score for participants without dementia. The most frequent disturbance reported for participants with dementia was apathy (27%). Depression and agitation/aggression were nearly as common, each reported in 24% of participants with dementia. The least frequent symptom was elation, reported in only 1%. Neuropsychiatric Inventory domain scores also reflected these frequencies, with apathy, depression, and agitation/aggression having the highest mean scores. In every Neuropsychiatric Inventory domain, both the proportion of participants with the disturbance and the mean Neuropsychiatric Inventory score were significantly higher in the participants with dementia than in the participants without dementia (for all logistic and linear regression models, p<0.01).
+Table 3 compares the prevalence of Neuropsychiatric Inventory disturbances in participants with Alzheimer’s disease and those with vascular dementia. In general, the prevalence of Neuropsychiatric Inventory disturbances was similar in the two groups (p>0.10 for linear and logistic regression models of either total Neuropsychiatric Inventory scores or domain scores for hallucinations, agitation/aggression, anxiety, apathy, irritability, elation, disinhibition, and aberrant motor behavior).
There were two differences between Alzheimer’s disease and vascular dementia in the logistic regression models: participants with Alzheimer’s disease were more likely to have delusions, and participants with vascular dementia were more likely to have depression (
+Table 3). In linear regression models, participants with vascular dementia had higher mean scores in the depression domain than participants with Alzheimer’s disease (beta=0.145, t=2.42, df=1, p=0.02). There were no other significant differences in the comparison of total and domain Neuropsychiatric Inventory mean scores between individuals with vascular dementia and those with Alzheimer’s disease (in all domains, p>0.07 in linear regression models).
+Table 4 shows the prevalence of individual Neuropsychiatric Inventory disturbances by dementia stage, as classified by the Clinical Dementia Rating. Differences in the prevalence of individual Neuropsychiatric Inventory disturbances across levels of severity of dementia were assessed in logistic regression models. Differences in the prevalence of agitation/aggression (13% in mild dementia, 24% in moderate dementia, and 29% in severe dementia) were statistically significant (
+Table 4). Differences in the prevalence of aberrant motor behavior (9% in mild, 17% in moderate, and 19% in severe dementia) were also statistically significant (
+Table 4). The differences in prevalence of hallucinations across Clinical Dementia Rating stages (8% in mild, 21% in moderate, and 15% in severe dementia) fell just short of statistical significance (
+Table 4). There were no other substantial differences in the prevalence of other Neuropsychiatric Inventory disturbances across Clinical Dementia Rating stages.
In the ANOVA of mean scores within the Neuropsychiatric Inventory domains, only depression showed statistically significant differences across Clinical Dementia Rating stages (F=5.86, df=1, 272, p=0.02). Scores in the depression domain increased with severity of dementia. There were no other significant differences in mean Neuropsychiatric Inventory domain or total scores (p>0.10 for all other linear and logistic regression models).