Participants in The 90+ Study
are survivors from the Leisure World Cohort Study (LWCS), an epidemiologic investigation of a retirement community in Orange County, CA (Leisure World, Laguna Woods). The LWCS was initiated when researchers mailed a health survey to all residents in the Leisure World retirement community [6
]. A total of 13,978 residents (61%) with a median age of 73 years returned the questionnaire. In addition to the original 1981 survey, cohort members were sent follow-up questionnaires in subsequent years. The Leisure World cohort is an ideal sample for studies of the oldest-old since it is an intact, highly cooperative cohort, with nearly all surviving members of the cohort aged 90+ years.
The 90+ Study was initiated in 2003 when the 1,146 surviving participants from the original LWCS who were aged 90 years and older on January 1, 2003 were invited to join. From the original 13,978 LWCS participants, the majority did not meet criteria for enrollment, either because they had died before January 1, 2003 (79%) or where younger than 90 years of age (13%). Of the 1,146 people who did meet criteria for participation, we were able to enroll 961 (84%) with the remaining either refusing (11%) or untraceable (5%). We also extended an invitation to join The 90+ Study to those participants from the original cohort who were 90 years and older on January 1, 2008 and to those who turn 90 thereafter. As of January 2010, about 1,400 participants had joined The 90+ Study.
Although it is not standardized to the whole U.S. Population, The 90+ Study is a population-based study because subjects comprise survivors of a study established in 1981 in a geographically defined area (The Leisure World Retirement Community). In addition, as described in the following sections, participants lived at home as well as in institutions, resided across the country, represent the full spectrum of health and cognitive abilities, and are representative of the oldest-old population in Orange County.
To maintain the population-based aspect of the cohort it was crucial to recruit as many people as possible from the original cohort. Given the advanced age of the participants and the full spectrum of cognitive and functional abilities, health status, and geographic locations, we provided much flexibility in terms of how and where evaluations took place.
All cohort members are initially asked to undergo a comprehensive in-person evaluation. In many cases, the evaluation is done at the clinic but very often participants cannot travel to the clinic and the evaluation is instead done at their place of residence, including assisted living facilities, and nursing homes. Sometimes participants, or their relatives on their behalf, do not agree to an in-person evaluation, usually due to frailty, cognitive impairment, or poor health. In such situations, we obtain information via telephone or mail either from the participants themselves or from their informants. Due to the advanced age of the cohort, we obtained information via telephone or mail from suitable informants for participants who had passed away before we were able to contact them.
Although most participants still resided in or near the Leisure World Community, about a third had moved out of the community often to be closer to relatives who could help care for them. In those situations, we visit participants at their homes and have traveled to 31 states to perform evaluations.
We have used several different strategies to trace and locate participants in the LWCS and 90+ Study. Participant’s addresses are kept up-to-date by mailing periodic newsletters to cohort members updating them of study findings. Addresses of those returned as undeliverable are updated with addresses provided by the post office. When participants cannot be located, we contact their next-of-kin. We also use internet and commercial databases to locate participants and their relatives.
The 90+ Study is composed of two main cohorts recruited from surviving participants of the original LWCS: the 1,146 who were aged 90 years and older on January 1, 2003 (2003 Cohort) and those who were aged 90 years and older on or after January 1, 2008 (2008 Cohort). As of January 2010, a total of 961 participants (84%) had been recruited to the 2003 Cohort and 402 participants (74%) had joined the 2008 Cohort.
Over 70% (N=814) of enrolled participants who were alive at first contact agreed to in-person longitudinal examinations. During every subsequent 6-month follow-up examination of the in-person subjects, we completed data collection on more than 94% of survivors, resulting in an excellent follow-up rate. We have completed two or more visits on over 700 participants, three or more visits on over 500 participants, and some participants have been seen as many as 14 times.
Brain donation is an important component of The 90+ Study and thus all participants evaluated in-person are invited to take part of The 90+ Autopsy Study. A total of 202 participants, about 35% of all participants with in-person clinical evaluations, had enrolled in The 90+ Autopsy Study as of January 2010. Given the rarity of well-characterized oldest-old subjects participating in neuropathological studies, we also enrolled a small group of 29 volunteers who approached us for participation in The 90+ Autopsy Study but who were not part of the original Leisure World Cohort. These volunteers were mostly friends and family of study participants. Although many participants sign up for the autopsy study after their initial visit, most have agreed after several visits, including participants who have consented after being seen more than 10 times. Thus, we continue to discus brain donation with participants during every visit. All participants evaluated in-person are invited to participate in The 90+ Autopsy Study, regardless of where they reside. For participants who live more than two hours away from UCI, we arrange for brain collection with local facilities, such as ADRCs, research universities, or hospitals. These facilities perform the brain removal according to a standard procedure and then ship the brain whole to UCI for autopsy.
As of January 2010, of the 202 participants enrolled in the Autopsy study, 120 autopsies had been completed on the 134 people who died, giving us an autopsy rate of 90%. As we continue to follow participants who have consented to brain donation and continue to enroll participants, we expect to have one of the largest collections of brains of oldest-old participants available for clinical-pathological studies.
The full clinical evaluation includes a neurological exam (with mental status testing and assessment of functional abilities) by a trained physician or nurse practitioner and a comprehensive neuropsychological test battery [7
] (including the Mini-Mental State Exam (MMSE; score range: 0–30) [8
]). Participants evaluated by phone complete the short version of the Cognitive Abilities Screening Instrument (CASI-short; score range: 0–34) [9
]. In addition, all participants (or their informants) are asked to provide information about demographics, past medical history, and medication use. Informants of all participants complete a mailed questionnaire about the participant’s cognitive status [10
] and functional abilities [11
]. The Dementia Questionnaire (DQ) [13
] is done over the phone with informants of participants who show signs of cognitive decline and for all participants shortly after their death, in order to obtain details about the onset of cognitive problems.
The assessments for The 90+ Study
were designed keeping in mind the advanced age of the participants and the high prevalence of medical comorbidities, motor limitations, and sensory losses in this population, factors that can affect the validity and reliability of the data obtained [15
]. To accommodate the wide variety of cognitive and physical abilities of the participants and to minimize missing data, we made modifications and allowances to the assessments and visits. For example, we provide printed instructions and sound amplifiers for participants with sensory impairments. We also use short forms of tests, keep visits as short as possible, provide frequent breaks, or divide visits into more than one session to minimize fatigue. The presence of comorbidities, sensory losses, and other limitations also make documenting functional loss due to cognitive difficulties in these oldest-old participants very challenging. To overcome these challenges, we modified our functional activities questions to probe in more detail about their functional abilities in order to help us differentiate between functional losses due to cognitive vs. other physical reasons. In addition, we rely heavily on relatives and caregivers of the participants for insight and information regarding functional abilities.
Another aspect of The 90+ Study
different from most studies is the short interval between evaluations. As these participants have a high incidence of dementia [16
] and disability [17
] and a fast rate of cognitive [15
] and functional decline, we repeat in-person evaluations every 6 months allowing us to capture fast and frequent changes in cognition and function in this very elderly group.
Cognitive Diagnosis Determination
A determination of cognitive status is made for all participants at every visit. For participants that are seen in-person, cognitive status is determined by a neurological examiner using only information from their current examination and the MMSE test results applying Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for dementia [18
]. Although examiners are not provided with data collected on previous visits to make their diagnoses, they are not completely blinded to previously collected information as they may have evaluated the same participants in multiple occasions. For participants not seen in-person, cognitive status is determined using other available information including the CASI-short or informant questionnaires (for details see [3
After a participant dies, another determination of cognitive status is done during a multidisciplinary diagnostic conference, this time using all available information, including the participants’ full evaluations, information collected from informants, laboratory tests, medical records, including CT or MRI scans of the head, and any other relevant studies. All the information is presented and discussed during the diagnostic conference led by the study principal investigator with conferees blinded to pathological diagnosis. Participants are classified as normal, cognitively impaired not demented (CIND), or demented (DSM-IV criteria). CIND is assigned when a participant has evidence of cognitive or functional loss but not of sufficient severity to meet criteria for dementia. If a participant is diagnosed with dementia, the primary and secondary etiologies of the dementia are specified as well as the date when dementia criteria were met.
Brain Tissue Collection and Pathological Evaluation
All procedures for procuring and preparing brain tissues are done according to the uniform datasets and forms of the National Alzheimer Coordinating Center (NACC) and the Alzheimer Disease Research Centers (ADRC). The NIA-Reagan Working Group [19
] modification of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) format [20
] is used as a standardized diagnostic protocol. The leader of the UCI ADRC Pathology Core performs all diagnostic pathologic evaluations blinded to cognitive diagnosis.