Dementia is an acquired condition characterized by a decline in at least 2 cognitive domains (loss of memory, attention, language, and visuospatial or executive functioning) that is severe enough to affect social or occupational functioning (7). Patients with dementia may also exhibit behavioral and psychological symptoms. The major dementia syndromes in older adults include Alzheimer disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, Parkinson disease with dementia, and dementia of mixed cause (8). Mild cognitive impairment is different from dementia in that the cognitive impairment is not severe enough to interfere with instrumental activities of daily life.
Dementia affects approximately 2.4 to 5.5 million Americans, but its prevalence is difficult to determine because of differences in definitions and populations used in studies (8–10). Age is the most important risk factor. Data from large population-based surveys indicate that the prevalence of dementia in the United States is 5% in persons aged 71 to 79 years, 24% in those aged 80 to 89 years, and 37% in those older than 90 years (8). Prevalence varies by race; prevalence in adults aged 71 years or older in 1 large study was 21.3% for blacks and 11.2% for whites (11). The prevalence of Alzheimer disease in Hispanics is approximately 1.5 times that seen in the white population (11–13). Dementia also affects more women than men. In persons aged 71 years or older, approximately 16% of women have dementia compared with 11% of men; these differences are primarily explained by women's longer life expectancy rather than any sex-based risk factors (14). Alzheimer disease accounts for 60% to 80% of all dementia, frontotemporal dementia accounts for 12% to 25%, 10% to 20% is considered vascular dementia, 5% to 10% is considered dementia with Lewy bodies, and 10% to 30% is considered dementia with mixed cause (8, 10, 15). It is difficult to estimate the prevalence of MCI, and estimates range widely, from 3% to 42% in adults aged 65 years and older, depending on the population and diagnostic criteria used (16, 17).

Background: The diagnosis of dementia requires both memory loss and at least one other type of cognitive impairment. The natural history of patients with severe memory loss but no other type of cognitive impairment is poorly understood. We studied progression to dementia in patients with isolated memory loss.

Methods: From a registry of 811 patients with cognitive complaints, 21 patients with severe isolated memory loss of unknown cause were identified and followed up for a mean of 48 months. A comparison group of 198 patients on the same register was identified with newly recognised cognitive complaints but without dementia or isolated memory loss (mean follow-up 31 months). We did a range of neuropsychological tests at intake.

Findings: During follow-up, 48% (n = 10) of patients with isolated memory loss-developed dementia compared with 18% (n = 36) of the comparison group. Life-table analysis showed the mean times to a diagnosis of dementia was 3.77 years (95% CI 2.99-4.56) and 5.96 years (5.60-6.31), respectively (p = 0.01). The neuropsychological tests did not predict which patients would progress to dementia.

Interpretation: Patients with severe isolated memory loss have an increased risk of developing dementia and should be closely followed-up.

Diagnosis of dementia is a stepwise process that involves examination of patient history and early warning signs, as well as performance screening, assessment of daily functioning, behavioral problems, and caregiver status, with possible referral to specialist clinics for more thorough assessment (Table 1).
Step 1: Prediagnostic Tests and Early Warning Signs
Before any diagnostic tests are performed, patient history, physical examination, and laboratory findings as well as input from family should be considered because these factors are paramount to the diagnosis of dementia (Table 1).33 In particular, family physicians should take into account any risk factors for AD that may be present, including older age, lower education, female sex, and family history of AD (Table 1).

We propose a two-step process for the assessment of dementia using standardized instruments. The family physician performs a screening consisting of taking a medical history, gathering information from relatives and friends of the patient, and administering the combined Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). Specialists examine patients with suspected dementia to confirm the diagnosis of dementia and, after a thorough differential diagnostic process, provide the family physician with recommendations for treatment. Specialists should perform neurological and psychiatric examinations, imaging (computer-assisted tomography [CT], magnetic resonance imaging [MRI]), and laboratory work-up. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) core neuropsychological battery is proposed to serve as a minimal data set that is internationally compatible. In addition, we recommend the Nurses' Observation Scale for Geriatric Patients (NOSGER) as a standard tool for functional assessment.

Importance: Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million. Observations: Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia. Conclusions and Relevance: Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited.

There is agreement among the guidelines that international consensus diagnostic
criteria should be used in the diagnostic process [8, 14, 16, 21]. Usage of the DSM-IV is recommended by three
guideline groups [8, 14, 21], while other diagnostic criteria recommended
include the ICD-10 and
NINCDS-ADRDA [8, 21]. The diagnosis should be made by
clinicians with experience in dementia assessment [14, 15, 21, 23]. Some guideline groups suggest referral to a
specialised dementia assessment centre or to specialist clinicians such as geriatricians, geriatric
psychiatrists or neurologists .
Diagnosing subtype dementia is more complex, with agreement that these diagnoses
should be made by clinicians with expertise in the differential diagnoses using
international standardised criteria [14, 15, 21, 23] (refer to Supplementary data, Table A5 available
in Age and Ageing online).
Imaging and/or ancillary tests for diagnosing dementia are addressed by nine
guideline groups. There is agreement that structural imaging, including computed
tomography (CT) or magnetic resonance imaging (MRI), should be performed at
least once in the workup [4, 6, 8, 14–16, 18, 21, 23]. Functional imaging is not
recommended routinely by the Ministry of Health Malaysia (MOH(M)), while other guideline groups suggest
using modalities such as perfusion hexamethylpropyleneamine oxime single-photon
emission computed tomography and 2-[18F]fluoro-2-deoxy-d-glucose
positron emission tomography when the diagnosis of dementia is uncertain after
performing structural imaging, or if differentiating among dementia subtypes is
required [5, 6, 15, 16, 18]. Only the EFNS group addresses amyloid imaging,
which they do not recommend for routine clinical use .

Eight guidelines address cognitive testing. There is agreement that a cognitive
assessment should be performed for those in whom carers describe cognitive
decline [4, 5, 14, 15, 18, 19, 23], using a valid,
standardised tool. Specific tools recommended vary (refer to Supplementary data,
Table A3 available in Age and Ageing online). Six guidelines recommend
performing neuropsychological testing, as an adjunct to the standard tools, in
mild or questionable cases of dementia [4, 5, 8, 14, 15, 18, 21].
There is agreement among the guidelines that international consensus diagnostic
criteria should be used in the diagnostic process [8, 14, 16, 21]. Usage of the DSM-IV is recommended by three
guideline groups [8, 14, 21], while other diagnostic criteria recommended
include the ICD-10 and
NINCDS-ADRDA [8, 21]. The diagnosis should be made by
clinicians with experience in dementia assessment [14, 15, 21, 23]. Some guideline groups suggest referral to a
specialised dementia assessment centre or to specialist clinicians such as geriatricians, geriatric
psychiatrists or neurologists .
Diagnosing subtype dementia is more complex, with agreement that these diagnoses
should be made by clinicians with expertise in the differential diagnoses using
international standardised criteria [14, 15, 21, 23] (refer to Supplementary data, Table A5 available
in Age and Ageing online).

4. The distinction between MCI and dementia is important and is currently made on the basis of clinical assessment of cognition and function. For screening purposes, examining the complaint with the patient and a family member and proceeding with an objective assessment of cognition and functional impairment should be done. 1A (88%)
5. An objective assessment of the patient's cognitive function could be achieved by using rapid psychometric screening tools such as the Memory Impairment Screen (MIS)22 + clock drawing test (CDT),23 the Mini-Cog,24 the AD8,25 the four item version of the MoCA (Clock-drawing, Tap-at-letter-A, Orientation, and Delayed-recall),26 and the GP Assessment of Cognition (GPCOG).27 2B (93%)