We screened Thai elders age 60 and above living in 42 villages in the catchment areas of the primary care unit (PCU) of Siriraj Hospital in late 2004-early 2006. The screening consisted of a comprehensive geriatric assessment to determine health status, functional status, cognitive function, mobility and balance, and possible disabilities. According to Persons with Disabilities Empowerment Act 2007 (B.E.2550) in Thailand, disability is classified into 5 domains: vision, hearing, daily function, neuropsychiatric issues, and cognition. We used a modified, culturally adapted Mini Mental State Examination (MMSE) called Thai Mental State Examination (TMSE) [11
], Thai Activity of Daily Living (ADL) [12
], Neuropsychiatric Inventory Questionnaire (NPI-Q) [13
], Clinical dementia rating scale (CDR) [15
], Thai Geriatric Depression Scale (TGDS) [16
], Tinetti gait assessment [17
], timed-get up and go test [18
], standard neuropsychological tests [19
] with culturally adjusted norms including tests of attention, memory, executive function, visuospatial function, and naming tasks. Hearing was assessed by standard audiometry. Profound hearing loss is described as being unable to hear a >90 deci Bell in the better ear. Visual acuity was assessed by using a pocket Jager chart. Severely impaired eyesight or blindness is defined by having corrected visual acuity <20/400 in both eyes. World Health Organization (WHO) quality of life was used to assess general health [27
]. History of falls in the past 1 month was recorded. All is defined by a sudden, unintentional change in position causing an individual to land at a lower level, on an object, the floor, the ground or other surface and having part of the body touching the ground. We diagnosed dementia by Diagnostic and Statistical Manual (DSM) IV criteria [28
] and MCI by modified Petersen’s criteria [29
]. SPSS 11 was used for statistical analysis. Blood tests to analyze possible reversible causes of dementia and ApoE gene status, brain MRI were offered to those with MCI, dementia and to 30 cases of normal elders to evaluate the cause of dementia and its comorbidity.
The DDP planned to follow individuals with MCI and dementia at 1–2 year interval and to follow 5-10% of individuals with non-dementia non MCI (non-case group) for the same period. At the follow up assessment, the cognition, function, and neuropsychiatric problems were reassessed.
Sample size estimation based on detecting progression from MCI to demetia is calculated by assuming that prevalence of MCI is 15%, prevalence of MCI progression is 12%, 2-sided of 95% confidence interval and allowable error is 4%. Therefore, a sample size of MCI should be 254 and the studied population should be 1,694 (Computer program – n Query Advisor). If there is 15% drop out, then the sample size would be 1,948.
The DDP have been performed with the approval from the Ethics Committee on Research Involving Human Subject of Faculty of Medicine Siriraj Hospital, Mahidol University (No.141/2003). Written informed consent for participation in the study was obtained from both participants and their relatives either spouse or children.
Inclusion criteria are as follows:
1. Elderly persons age 60 and above who register to obtain primary care service at the PCU of Siriraj Hospital.
2. Elderly persons and caregivers who agree to participate with the study for the 3 year period.
3. Elderly persons who live within 20 kilometers from Siriraj Hospital.
Exclusion criteria are as follows:
1. Elderly persons or caregivers who do not wish to join the DDP study or are unable to give an informed consent.
2. Elderly persons who drop out because of the presence of severe illnesses (cardiac, hepatic or renal failure, cancer or other relevant systemic diseases) at the follow up, and who have severe illnesses at baseline and refuse to participate with the DDP study.
3. Severe psychiatric disorders.
A structured and comprehensive questionnaire was administered by trained personnel to the patient and care partner and included information on demographic characteristics, education, occupational status defined as longest job in life, marital status, living conditions, lifestyle habits (alcohol consumption, smoking), vascular risk factors and current medical problems. Elders and caregivers were purposely asked if elders had any memory complaint or similar problem. Blindness and severe hearing loss were determined with the assessment.
Functional and clinical assessments
Mobility is assessed by timed get up and go test (TUG) and Tinetti gait assessment score. TUG starts with an individual rising from a chair, walking 3 meters, turning around, returning to the chair, and siting down. TUG test measures the time taken to complete the test. One practice trial is given before the test. Results of <10 seconds indicates freely mobile, <20 seconds - mostly independent, 20–29 seconds - variable mobility, and >20 seconds suggests impaired mobility. The grading of get up and go (GUG) [30
] is modified into 5 grades in which 1 is normal or no fall risk and 5 is severely abnormal or very high fall risk. The Tinetti balance and gait evaluation is divided in two parts: the first part studies balance defects based on 9 postural situations and the second part studies gait. The maximum score is 28 in which a higher score indicates a better balance and gait performance. Activities of daily living (ADLs) are assessed by utilizing the Thai ADL scale which consists of 6 basic ADLs and 7 instrumental ADLs and scored as 01, 2. A higher score of Thai ADLs indicates poorer daily function.
The NPI-Q assesses 12 neuropsychiatric including mood, psychotic, vegetative, and frontal related symptoms or behaviors. It starts with asking if the symptom is present (1= yes, 0= no) and asking about the severity of the symptoms (1= mild, 2= moderate, 3=severe). The NPI includes additional frequency assessment that scoring 1 to 4 (1 = occasionally, less than once per week; 4 = very frequently, once or more per day or continuously). The NPI-Q was used at the screening phase at baseline and the NPI was used in those who came into the second phase of the study to assess their dementia and MCI status. Caregivers or family members familiar with the individual’s behavior are interviewed using scripted questions. The caregiver is asked if the individual’s behavior has changed during the past month. Thai GDS consists of 30 questions; a higher score signifies more depressive symptoms. Score 0–12 implies no depression, score 13–18 suggests mild depression, score 19–20 indicates moderate depression, and score 25–30 denotes severe depression. An individual is asked to consider if the symptoms are present in the past 1 week. The CDR is a global assessment instrument of dementia that yields global and sum of boxes (SB) scores, with the global score being indicative of stage dementia severity while CDR-SB being considered a more detailed quantitative general index than the global score [31
]. The CDR assesses 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available).
TMSE is a screening tool for cognitive impairment. Those with TMSE ≤ 26 were recruited to evaluate cognitive status. 5-10% of cognitively normal elderly were examined (74 cognitively normal elderly, 5.05%). The DDP is also interested in the association of cognition and other chronic diseases. Comorbid diseases that are included in this study are hypertension (BP≥140/90 mmHg or on antihypertensive drugs); pulmonary diseases (such as chronic obstructive pulmonary disease: having history of chronic progressive symptoms namely cough and/or wheeze and/or breathlessness with objective evidence of airways obstruction that does not return to normal with treatment, taking medication to help ventilation/breathing problems, asthma, and restrictive lung diseases); heart disease (coronary heart disease, valvular heart disease, and heart failure); thyroid diseases (hypothyroidism, hyperthyroidism, or taking medication for thyroid); diabetes mellitus (taking hypoglycemic drugs, taking regular insulin injection, or fast blood sugar ≥126 mg%); arthritis (history of or on examination present osteoarthritis (OA). (OA of the knee is characterized by knee pain for most days of the prior month, OA of the hand is characterized by hand pain, aching or stiffness for most days of the prior month, OA of the hip with hip pain for most days of the prior month); crystal induced arthritis, and rheumatoid arthritis); cerebrovascular disease (taking platelet anti aggregation drugs and a history of previous stroke, having a history of stroke, or hemiparesis on neurological examination); smoker (current or active smoking); and alcohol drinker (current or active alcohol drinking). The World Health Organization (WHO) defines health as a state of complete physical, mental, and social well-being, not merely the absence of disease and has invented a measurement of the improvement in the quality of life related to health care. WHO describes Quality of Life (QoL) [27
]as an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals. The WHOQOL-BREF in this study is based on a four domain structure: physical health, psychological health, social relationships, and environment. The WHOQOL-BREF is self-administered to elderly individuals with family members or caregivers as assistants. Standardized instructions were read to respondents when the assessment is interviewer-administered. The WHOQOL-BREF initial raw scores are converting to transformed scores with the second transformation converting domain scores to a 0–100 scale. The initial rating score ranges from 1 (very dissatisfied, never, not at all, very poor) to 5 (very satisfied, always, extremely, very good).
Magnetic resonance imaging study
All MCI, dementia, and some cognitively normal elderly subjects were offered a brain MRI study within 6 months after the diagnosis of dementia or MCI was made. A total of 223 subjects had brain MRI. The MRI scan was done with 1.5T. (Intera, Philips, the Netherlands) field strength. The protocol composed of 3D-T1wi in coronal plane perpendicular to temporal lobe axis (iso-voxel 1×1×1 mm), axial FLAIR and T2wi (thickness 5 mm). The 3D-T1wi was reformatted to axial plane and used for volumetric measurement of hippocampus. Axial gradient echo T2wi was performed in some cases. Visual rating scale of medial temporal lobe area (MTA) [32
], Fazekas WML [33
], and Scheltens WML rating scale (SS) [34
] were utilized in brain MRI reading by radiologist (O. Chawalparit, OC) and neurologist (V. Senanarong, VS). Volumetric study by region of interest (ROI) technique was done by OC and VS. VS and OC obtained rater standardization evaluation with a weighted kappa variance score <10%. The WMLs were visually rated on the axial FLAIR image with the use of two semiquantitative rating scales. The Fazekas scale is a four-point scale (none, mild, moderate, severe) rating the extent and severity of the deep white matter changes and the Scheltens scale, in which WMLs are rated 0–6 in 13 subcortical regions, including the basal ganglia and infratentorial region, and 0–2 in 3 periventricular regions, resulting in a total range of 0–84. The global cortical atrophy (GCA) [35
] was rated on the axial FLAIR image using a 4-point visual rating scale (0 = none, 1 = widening of sulci, 2 = atrophy of gyri, 3= end stage atrophy with ‘razor-blade’ gyri). The MTA was visually rated on 3D-T1wi in coronal plane using a 5-point scale (0 = none, 1 = widening of Choroid fissure, 2 = widening temporal horn, opening fusiform and collateral sulcus, 3 = profound volume loss hippocampus, 4 = end stage atrophy).
Clinical data on daily function, cognition, and neuropsychiatric symptoms were reassessed in MCI, dementia and cognitive normal elderly (30 cases in this study) at a 1–2 year interval. In this study the mean follow up time on 288 subjects is 529.96 days (SD=230.73 days, median 433 days, min 272 days, max 1,312 days). Evolution of cognitive function especially to a diagnosis of dementia was assessed at the follow up, by a consensus group (neurologists, psychologists, radiologist and physicists).
Statistical analysis was performed using SPSS 11 (SPSS Inc., Chicago, IL) We examined baseline demographics, risk factors, and comorbid features by assessing significance by means of Chi square test for categorical variables. We assessed the association between activities of daily living and vascular risk factors or relevant predictors with Pearson or Spearman correlation coefficient of the whole data and then performed linear regression analysis. We assessed the association between WML, cognitive function and general brain atrophy with Pearson correlation coefficient. The subjects with MCI or dementia and cognitively normal elderly were compared across demographic characteristics (age, sex, education, living conditions, employment status) using t tests. Risk factors of cognitive decline were compared using one-way ANOVA with Bonferoni adjustment or Chi square test. Epi info 6 was used to find 95% confidence interval of the prevalence and odds ratio. P<0.05 is considered to be of statistical significance.