Dementia: from prevention to
cure
Christopher Patterson
McMaster University,
Hamilton, Ontario
Canada
Objectives
• Define dementia
• Describe epidemiology of dementia in
India
• Distinguish the common types of dementia
• Des...
Dementia: A syndrome
• An acquired disorder
• Diffuse cognitive deficits: memory
(usually) aphasia, apraxia, agnosia,
exec...
Prevalence of dementia in India
• Low estimate 1.9% over age 65
(Ferri C et al Lancet 2005; 366: 2112)
• Higher estimate 2...
Highest estimate of prevalence:
Kerala India
• Door to door survey
• Screen with MMSE
• Full assessment if < 23
Age 65-69 ...
Global burden of Dementia
10/66 Dementia Research Group
Risk Factors for Alzheimer’s disease
• Age
• Family history
• Lifestyle
Physical exercise
Mental exercise
Diet
Tobacco
Hea...
Risk Factors for Alzheimer’s disease
Risk Factors for Alzheimer’s disease
Can we predict who will develop
dementia?
Knowing the following risk factors in middle age
a calculation of future likelih...
Calculating future risk
Patterson C et al CMAJ 2008; 178:548
Types of Dementia
• Alzheimer’s
• Mixed
• Lewy-body
• Frontotemporal
• Vascular
• Other neurodegenerations (e.g.Huntingdon...
Types of Dementia
• Alzheimer’s
• Mixed ► 80% of all dementias
• Lewy-body
• Frontotemporal
• Vascular
• Other neurodegene...
VaDVaD ADADMixed
Interactions Between Vascular
Dementia and Alzheimer’s
Disease
80% of all Dementias80% of all Dementias
The Nun Study
• Longitudinal study of the Teaching Sisters of
Notre Dame (USA)
• 678 enrolled since 1991 aged 75-102
• Wri...
The Nun Study
• Early linguistic ability predicts later
dementia
• Severity of Alzheimer changes (amyloid
plaques, neurofi...
The Nun Study: pathology of those
with dementia
Alzheimers alone 43%
Mixed (AD + strokes) 34%
Other types of pathology 20%...
Pure vascular dementia
is relatively rare
• Several clinicopathological studies
• Vascular dementias suspected commonly
in...
Symptomatic Domains of AD
Over Time
Mood
Cognitive
Function
Functional
Autonomy
Behaviour
Problems
Adapted from Gauthier e...
Natural History of AD
Time (years)Time (years)
SymptomsSymptoms
DiagnosisDiagnosis
Loss of functionalLoss of functional
in...
Alzheimer’s Disease
Progresses Through Distinct
Stages
MildMild ModerateModerate
SevereSevere
• Memory lossMemory loss
• L...
Alzheimer’s disease anatomical
correlates: 3 phases of illness
• Limbic system: memory
• Parietal: spatial organization, f...
Cholinergic Pathways From the
Basal Forebrain
P
C
OC
F
C B
F H
Frontotemporal Dementia
Frontotemporal dementia
3 clusters of features:
(a) Behavioural (disinhibition, apathy, poor
insight and judgement)
(b) La...
Frontotemporal dementia
• Familial in 50%
• Serotoninergic (vs. cholinergic) deficit
• Memory not a prominent feature unti...
Lewy (or Lewey) body
dementia
Also known as:
• Dementia with Lewy bodies
• Lewy body dementia
Lewy body dementia
Core features (2 probable, 1 possible):
• Fluctuating cognition
• Recurrent well formed detailed visual...
Lewy body dementia
Supportive features:
• Repeated falls
• Systematized delusions
• Dementia occurs before or concurrently...
Lewy body dementia
• Severe cholinergic deficit
• Anti Parkinsonian medications may
worsen psychosis
• Antipsychotic agent...
Vascular dementia
• Dementia follows in wake of stroke
• Presentation will depend upon location
and size of stroke
• Clear...
Multiple large
vessel infarcts
Bilateral strategic
thalamic infarcts
Binswanger’s
disease
Brain Imaging of Vascular
dement...
Assessment of Dementia:
domains
• Cognitive
• Functional
• Behavioural
• Affective
80 year old lady
• Brought to you by only daughter
• Forgot daughter’s birthday this year
• Missed payment of several bill...
80 year old lady: history
80 year old lady: history
• Onset and duration
• Focal neurological symptoms
• Precipitating events
• Past history and ris...
80 year old lady: examination
80 year old lady: examination
• Overall appearance (e.g. cleanliness,
grooming, trauma, clothing)
• General physical ( e.g...
80 year old lady: mental status
80 year old lady: mental status
• MMSE or equivalent
• Clock drawing
• Montreal Cognitive Assessment (MoCA)
• Measures of ...
80 year old lady: laboratory
80 year old lady: laboratory
• CBC
• Blood sugar
• Electrolytes
• TSH
• B12
• Calcium
80 year old lady: neuroimaging
80 year old lady: neuroimaging
• Age under 65
• Focal neurological symptoms
• Focal neurological signs
• Short history
• H...
80 year old lady: management
80 year old lady: management
• Disclosure
• POA, advance directives
• Risk assessment (consider OT)
• Transport
• Educatio...
68.8
100.5
113.4
120.0
0
20
40
60
80
100
120
140
Mild Mild-to-moderate Moderate Severe
HourspermonthspentcaringforADpatien...
A Family Intervention for people
with AD
97 dyads (care giver plus patient ) NYC
Intervention:
 2 individual and 4 family...
A Family Intervention for people
with AD
Control group received “usual care”
Follow up to 8 years
Results:
Median time to ...
“Behavioural” Interventions
• Establish routine
• Day programs e.g activities, exercise,
socializing
• In home respite
• D...
80 year old lady: management
• Disclosure
• POA, advance directives
• Risk assessment (consider OT)
• Transport
• Educatio...
Cholinesterase Inhibitors
• Have become standard of treatment for
mild to moderate Alzheimers Disease ( but
also show effi...
Clinical
improvement
Clinical
decline
No change
0 Week 24
LOCF
(72)
(73)
4
n=69
n=70
12
68
62
18
64
64
8
61
61
24
62
63
Do...
Cholinesterase Inhibitors: do they
work?
• Donepezil (Aricept)
• Rivastigmine (Exelon)
• Galantamine (Reminyl)
• All show ...
PREVENTING DEMENTIA
We can reduce the incidence of strokes by:
• Control of blood pressure
• Control of other vascular ris...
Preventing Dementia:
The SYST-EUR Study
• Multicentre RCT in Europe 2470 participants
over age 60; SBP 160-319
• Target: r...
What is new in
Pharmacological Treatment?
• Memantine for AD
• Vaccination against AD
• Antibiotics for AD
• Lipid lowerin...
Memantine
• NMDA antagonist modulates glutamate
excitotoxicity
• 28 week RCT involving 252 people with
moderate to severe ...
Vaccination
• Anti Abeta immunotherapy reduces
amyloid deposition and improved spatial
cognition in mice
• Clinical trial ...
Vaccination
• In subgroup of 30 patients, those who
generated Abeta antibodies had reduced
disease progression
• Attempts ...
Antibiotics for AD
• Higher than normal titres of Chlamydia in
people with AD
• Multicentre Canadian double blind
placebo ...
Antibiotics for AD
• Standardized ADAS Cog @ 6 months difference
of 2.75/70 between treated and placebo group
(significant...
Lipid lowering and AD
• Previous observations suggested lower
risk of AD in those taking “statins”
• Recently presented at...
SUMMARY
• Dementia relatively uncommon in India at
present, but prevalence will rise sharply
with aging of population
• Be...
Dementia: from prevention to cure
Dementia: from prevention to cure
Dementia: from prevention to cure
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  • Vascular dementia is the second most common form of dementia, after Alzheimer’s disease. It is also thought that the prevalence of mixed vascular dementia (i.e. AD with cerebrovascular disease) has largely been underestimated. And in fact, problematic clinical settings arise when the course of the dementia conflicts with current understanding of the illness (e.g., insidious onset and/or slow progression in VaD patients) or in cases where there are difficulties assessing less extensive lesions / infarcts.
    The medical communities are starting to view individual dementias, not as separate entities, but rather as part of a dementia continuum. This is based on the fact that differentiation between AD and vascular dementia is often times difficult due to the large overlap in vascular risk factors (e.g., cerebrovascular disease, arterial hypertension) and vascular pathology (e.g., lacunae, WMLs). In both diseases, cognitive impairment is the key symptom of dementia and regardless of the underlying cause, pharmacological intervention aims to enhance neurotransmission. Additionally, in patients with mixed dementia, the deficits related solely to the AD component are expected to respond to AChE inhibition, as previously proven from the AD studies. Galantamine aims to provide benefit to patients with probable VaD, probable AD or a combination of AD with cerebrovascular disease such that regardless of etiology, symptomatic treatment exists.
    Reference
    Erkinjuntti T. Cerebrovascular Dementia Pathophysiology, Diagnosis and Treatment. CNS Drugs 1999 Jul;12(1):35-48.
  • Key Points
    Different symptom domains present themselves at different times during the course of AD, and while some deteriorate over the whole course, other symptoms arise at one stage, only to subside at a later stage.1
    The mean course of AD is 8 to 12 years after onset of symptoms.2
    Early in the disease course, mood symptoms like depression and anxiety are noticeable, however, these symptoms typically recede in the moderate stages.1
    Cognitive decline begins early on and progresses until cognition is deteriorated completely.1
    Loss of functional autonomy begins shortly following the first signs of cognitive decline. Its progress is steady, but slower than the cognitive decline.1
    Later in the disease progression, AD patients tend to develop behavioural problems, which eventually abate, as well as Parkinson-like motor changes.1
    References
    1.Gauthier S et al. The future diagnosis and management of Alzheimer’s disease. In: Gauthier S, editor. Clinical Diagnosis and Management of Alzheimer’s Disease. 2nd rev. ed. London: Martin Dunitz, 1999.
    2.Barclay LL et al. Survival in Alzheimer’s disease and vascular dementias. Neurology 1985;35:834-840.
  • The neuronal degeneration caused by AD results in changes to cognitive function, daily functioning and behaviour along with associated neuropsychiatric symptoms.
    This natural history curve illustrates the degeneration seen with AD in reference to the Mini-Mental State Examination (MMSE).
    The time of onset of AD may vary between 45 and 95 years however the first symptoms of AD generally occur in patients over 60 years of age.
    Patients with AD (or a caregiver) tend to date the onset of symptoms at about 2–3 years before the diagnosis is made, but the time lag between onset and diagnosis can vary from 2–7 years.
    Death generally occurs within 8–10 years from the initial diagnosis, although this can range from 5–15 years.
  • In the early stages of AD, tasks requiring sustained attention, memory and problem solving abilities begin to deteriorate. In some patients progression can be rapid.
    As AD progresses, patients develop moderate to severe memory deficits, and increased language impairment.
    In the severe stages of AD, patients exhibit aphasia (loss of language), apraxia (loss of purposeful movement) and agnosia (loss of recognition).
    Approximately two thirds of AD patients will begin to exhibit behavioural problems encompassing a range of symptoms including
    Anxiety
    Depression
    Aggression
    Wandering
    These symptoms tend to emerge in the more advanced stages of AD.
  • Key Points
    While it is easy to understand that large infarcts are associated with VaD, it is also important to remember that VaD can be caused by smaller lesions.
    A small injury, lacunar in nature in a strategic location can also disturb communication, coordination and executive function.
    Reference
    Source of Images: Stephen Salloway, MD, from the talk Clinical Neurochemistry and Neuroimaging at the 2001 Board Review Meeting.
  • Key Points
    Data from the Canadian Study of Health and Aging, a community-based survey of the prevalence of dementia, including subtypes such as AD, among elderly Canadians, were used to examine the relationship between the severity of AD, as the mean annual cost of caring for an AD patient increases with the severity of the disease and the costs of caring.
    The time dedicated to providing direct care to patients with AD increases with the severity of the disease, with severe AD patients in the community requiring nearly twice as much care.
    Reference
    Hux MJ et al. Relation between severity of Alzheimer&amp;apos;s disease and costs of caring. CMAJ 1998;159(5):457-465.
  • Key Points
    Donepezil treatment improved global function in the advanced AD subgroup, with significant improvement versus placebo on the CIBIC-plus at each visit, as well as endpoint (last observation carried forward [LOCF] analysis).
    Reference
    Gauthier S et al. Donepezil shows significant benefits in global function, cognition, ADL and behavior in patients with severe Alzheimer&amp;apos;s disease. Neurology 2003;60(5, Suppl.1):A413:S48.005.  
  • Dementia: from prevention to cure

    1. 1. Dementia: from prevention to cure Christopher Patterson McMaster University, Hamilton, Ontario Canada
    2. 2. Objectives • Define dementia • Describe epidemiology of dementia in India • Distinguish the common types of dementia • Describe “standard” investigation of suspected dementia • Introduce principles of management • Touch on future trends
    3. 3. Dementia: A syndrome • An acquired disorder • Diffuse cognitive deficits: memory (usually) aphasia, apraxia, agnosia, executive dysfunction • Deficits sufficient to interfere with daily function • Not occurring solely in delirium or depression CMAJ 1999;160 (12 suppl)
    4. 4. Prevalence of dementia in India • Low estimate 1.9% over age 65 (Ferri C et al Lancet 2005; 366: 2112) • Higher estimate 2.7% over age 65 (Kalaria R et al Lancet Neurology 2008; 7:812)
    5. 5. Highest estimate of prevalence: Kerala India • Door to door survey • Screen with MMSE • Full assessment if < 23 Age 65-69 70-74 75-79 80-84 85-89 90+ % 0.6 2.0 5.2 7.1 11.8 13.3 Shaji S et al Br J Psychiatr 2005; 186: 136
    6. 6. Global burden of Dementia 10/66 Dementia Research Group
    7. 7. Risk Factors for Alzheimer’s disease • Age • Family history • Lifestyle Physical exercise Mental exercise Diet Tobacco Head injury • Hypertension • Elevated serum cholesterol • Elevated serum homocysteine
    8. 8. Risk Factors for Alzheimer’s disease
    9. 9. Risk Factors for Alzheimer’s disease
    10. 10. Can we predict who will develop dementia? Knowing the following risk factors in middle age a calculation of future likelihood of dementia: • Age • Level of permits education • Systolic BP • BMI • Total serum cholesterol • Degree of physical activity Patterson C et al CMAJ 2008; 178:548
    11. 11. Calculating future risk Patterson C et al CMAJ 2008; 178:548
    12. 12. Types of Dementia • Alzheimer’s • Mixed • Lewy-body • Frontotemporal • Vascular • Other neurodegenerations (e.g.Huntingdon’s) • Infections (e.g. HIV,Jakob-Creutzfeld)
    13. 13. Types of Dementia • Alzheimer’s • Mixed ► 80% of all dementias • Lewy-body • Frontotemporal • Vascular • Other neurodegenerations (e.g.Huntingdon’s) • Infections (e.g. HIV,Jakob-Creutzfeld)
    14. 14. VaDVaD ADADMixed Interactions Between Vascular Dementia and Alzheimer’s Disease 80% of all Dementias80% of all Dementias
    15. 15. The Nun Study • Longitudinal study of the Teaching Sisters of Notre Dame (USA) • 678 enrolled since 1991 aged 75-102 • Written autobiographies within 2 years of entry • Annual cognitive testing • Brain autopsies • 400 deceased by 2003 Snowdon DA Ann Intern Med 2003;139: 450
    16. 16. The Nun Study • Early linguistic ability predicts later dementia • Severity of Alzheimer changes (amyloid plaques, neurofibrillary tangles) did not always correlate with cognitive changes • Presence of stroke (especially small WM) increased clinical dementia (RR=20)
    17. 17. The Nun Study: pathology of those with dementia Alzheimers alone 43% Mixed (AD + strokes) 34% Other types of pathology 20% Vascular alone 2.5%
    18. 18. Pure vascular dementia is relatively rare • Several clinicopathological studies • Vascular dementias suspected commonly in life • At autopsy, vascular pathology alone rarely explained clinical features • Mixed pathology common • BUT may be more common in Asian counties
    19. 19. Symptomatic Domains of AD Over Time Mood Cognitive Function Functional Autonomy Behaviour Problems Adapted from Gauthier et al. Clinical Diagnosis and Management of Alzheimer’s Disease, 1999. Time Deterioration Motricity (Motor Function)
    20. 20. Natural History of AD Time (years)Time (years) SymptomsSymptoms DiagnosisDiagnosis Loss of functionalLoss of functional independenceindependence Behavioural problemsBehavioural problems Nursing home placemenNursing home placemen tt DeathDeath Mini-MentalStateExamination(MMSE)Mini-MentalStateExamination(MMSE) Early diagnosisEarly diagnosis Mild-to-moderateMild-to-moderate SevereSevere 11 22 33 44 55 66 77 88 99 00 55 1010 1515 2020 2525 3030 Reproduced with permission from Feldman and Gracon, 1996.Reproduced with permission from Feldman and Gracon, 1996.
    21. 21. Alzheimer’s Disease Progresses Through Distinct Stages MildMild ModerateModerate SevereSevere • Memory lossMemory loss • LanguageLanguage problemsproblems • Mood swingsMood swings • PersonalityPersonality changeschanges • DiminishedDiminished judgmentjudgment •Behavioural, personalityBehavioural, personality changeschanges •Unable to learn/recall newUnable to learn/recall new informationinformation •Long-term memory affectedLong-term memory affected •Wandering, agitation,Wandering, agitation, aggression, confusionaggression, confusion •Require assistance w/ADLRequire assistance w/ADL •Gait, incontinence,Gait, incontinence, motor disturbancesmotor disturbances •BedriddenBedridden •Unable to perform ADLUnable to perform ADL •Placement in LTC neededPlacement in LTC needed Average duration 7-10 yearsAverage duration 7-10 years StageStage SymptomsSymptoms
    22. 22. Alzheimer’s disease anatomical correlates: 3 phases of illness • Limbic system: memory • Parietal: spatial organization, function • Frontal: behaviour
    23. 23. Cholinergic Pathways From the Basal Forebrain P C OC F C B F H
    24. 24. Frontotemporal Dementia
    25. 25. Frontotemporal dementia 3 clusters of features: (a) Behavioural (disinhibition, apathy, poor insight and judgement) (b) Language (progressive expressive type aphasia, contraction of language) (c) Self neglect First described by Arnold Pick
    26. 26. Frontotemporal dementia • Familial in 50% • Serotoninergic (vs. cholinergic) deficit • Memory not a prominent feature until late • Often difficult to manage
    27. 27. Lewy (or Lewey) body dementia Also known as: • Dementia with Lewy bodies • Lewy body dementia
    28. 28. Lewy body dementia Core features (2 probable, 1 possible): • Fluctuating cognition • Recurrent well formed detailed visual hallucinations • Spontaneous Parkinsonism Suggestive features (1 possible, 1 plus above, probable: • REM sleep disorder • Severe neuroleptic sensitivity McKeith I, et al Neurology 2005; 65: 1863
    29. 29. Lewy body dementia Supportive features: • Repeated falls • Systematized delusions • Dementia occurs before or concurrently with Parkinsonism • Early visuospatial dysfunction • May progress more rapidly than AD
    30. 30. Lewy body dementia • Severe cholinergic deficit • Anti Parkinsonian medications may worsen psychosis • Antipsychotic agents may worsen Parkinsonism • Cholinesterase inhibitors often work well
    31. 31. Vascular dementia • Dementia follows in wake of stroke • Presentation will depend upon location and size of stroke • Clear history of stroke not always present • Large overlap with Alzheimer’s disease (i.e. mixed dementia)
    32. 32. Multiple large vessel infarcts Bilateral strategic thalamic infarcts Binswanger’s disease Brain Imaging of Vascular dementia 3 Types of VaD Source: Stephen Salloway, MD
    33. 33. Assessment of Dementia: domains • Cognitive • Functional • Behavioural • Affective
    34. 34. 80 year old lady • Brought to you by only daughter • Forgot daughter’s birthday this year • Missed payment of several bills • Housework and personal hygiene slipping slightly
    35. 35. 80 year old lady: history
    36. 36. 80 year old lady: history • Onset and duration • Focal neurological symptoms • Precipitating events • Past history and risk factors • Social history and risks (fire, wandering, summoning help, low TI medications) • Medications (all of them) • Order lab tests?
    37. 37. 80 year old lady: examination
    38. 38. 80 year old lady: examination • Overall appearance (e.g. cleanliness, grooming, trauma, clothing) • General physical ( e.g. HF, hypoxia, thyroid, tumours) • Focal neurological signs • Gait, balance
    39. 39. 80 year old lady: mental status
    40. 40. 80 year old lady: mental status • MMSE or equivalent • Clock drawing • Montreal Cognitive Assessment (MoCA) • Measures of insight & judgement
    41. 41. 80 year old lady: laboratory
    42. 42. 80 year old lady: laboratory • CBC • Blood sugar • Electrolytes • TSH • B12 • Calcium
    43. 43. 80 year old lady: neuroimaging
    44. 44. 80 year old lady: neuroimaging • Age under 65 • Focal neurological symptoms • Focal neurological signs • Short history • Head trauma • Anticoagulants or bleeding • Malignancy that might metastasize • Atypical features i.e. not suggesting AD
    45. 45. 80 year old lady: management
    46. 46. 80 year old lady: management • Disclosure • POA, advance directives • Risk assessment (consider OT) • Transport • Education and support • Alzheimer’s Society or other support organization • Case manager • Education sessions • Medications
    47. 47. 68.8 100.5 113.4 120.0 0 20 40 60 80 100 120 140 Mild Mild-to-moderate Moderate Severe HourspermonthspentcaringforADpatients AD Caregiver Time by Disease Severity Hux et al. CMAJ, 1998.
    48. 48. A Family Intervention for people with AD 97 dyads (care giver plus patient ) NYC Intervention:  2 individual and 4 family counselling sessions (education & resource information) After 4 months caregivers meet weekly in support groups Continuously available counsellors
    49. 49. A Family Intervention for people with AD Control group received “usual care” Follow up to 8 years Results: Median time to nursing home placement increased by 329 days p=0.02 RR of NH admission 0.65 (0.45,0.94) Effects most marked on those with mild and moderate dementia Mittelman S et al JAMA 1996
    50. 50. “Behavioural” Interventions • Establish routine • Day programs e.g activities, exercise, socializing • In home respite • Distraction, coaching • Behavioural observation
    51. 51. 80 year old lady: management • Disclosure • POA, advance directives • Risk assessment (consider OT) • Transport • Education and support • Alzheimer’s Society or other support organization • Case manager • Education sessions • Medications
    52. 52. Cholinesterase Inhibitors • Have become standard of treatment for mild to moderate Alzheimers Disease ( but also show efficacy in vascular and Lewy body dementia) • 25-33% of people treated show a noticeable improvement • Questionable disease stabilization • Probably all equally efficacious
    53. 53. Clinical improvement Clinical decline No change 0 Week 24 LOCF (72) (73) 4 n=69 n=70 12 68 62 18 64 64 8 61 61 24 62 63 Donepezil Placebo p=0.0004 p=0.0017 p=0.0007 p=0.0006 p=0.002 p=0.0002 ∆ = 0.7 CIBIC-plusCIBIC-plus Donepezil in Advanced AD (sMMSE 5-12):Global Function 3.4 3.6 3.8 4.0 4.2 4.4 4.6 4.8 5.0 5.2 Study week LSmeanscore±SE Donepezil Placebo Gauthier S et al. Neurology, 2003.
    54. 54. Cholinesterase Inhibitors: do they work? • Donepezil (Aricept) • Rivastigmine (Exelon) • Galantamine (Reminyl) • All show modest positive effects on: ADAS-Cog: WMD -2.62; -3.41; -2.77 CIBIC+: RR 1.37; 1.77; 1.28 AHRQ publication No. 04-E018-2 April 2004
    55. 55. PREVENTING DEMENTIA We can reduce the incidence of strokes by: • Control of blood pressure • Control of other vascular risk factors: Smoking, Cholesterol • Regular physical exercise (dancing…)
    56. 56. Preventing Dementia: The SYST-EUR Study • Multicentre RCT in Europe 2470 participants over age 60; SBP 160-319 • Target: reduction of SBP by 20 mm or <150mm by nitrendipine 10-40mg • Up to 5 years follow up • After 2 years 11 new cases of dementia in treated; 21 in placebo p=0.06 • Rate of dementia 3.8 vs 7.7 cases per 1000 person years p= 0.05 Forette F et al Lancet 1998; 352:1347
    57. 57. What is new in Pharmacological Treatment? • Memantine for AD • Vaccination against AD • Antibiotics for AD • Lipid lowering agents for AD • A word of caution about novel neuroleptics
    58. 58. Memantine • NMDA antagonist modulates glutamate excitotoxicity • 28 week RCT involving 252 people with moderate to severe AD (MMSE 3-14) • Significant improvements on CIBIC plus .5/5; Severe ADL 3/7 & SIB in treated group cf placebo • Well tolerated • Approved in USA, likely in Canada within next year Reisberg et al New Engl J Med 2003;348:1333
    59. 59. Vaccination • Anti Abeta immunotherapy reduces amyloid deposition and improved spatial cognition in mice • Clinical trial in 298 patients with AD:18 developed inflammatory meningoencephalitis: study halted • Autopsy in one: “less amyloid than expected” Orgogozo J-M et al Neurology 2003;61:46 Mathews P & Nixon R Neurology 2003;61:7
    60. 60. Vaccination • In subgroup of 30 patients, those who generated Abeta antibodies had reduced disease progression • Attempts being made to reformulate vaccine • Passive immunization considered Hock C et al.Neuron 2003;38:547 Wolfe MS. Nat RevDrug Discov 2002;1:859
    61. 61. Antibiotics for AD • Higher than normal titres of Chlamydia in people with AD • Multicentre Canadian double blind placebo controlled RCT • 101 patients with mild to moderate AD (MMSE 11-25) • Daily doxycycline 200mg plus rifampin 300mg or placebo for 3 months
    62. 62. Antibiotics for AD • Standardized ADAS Cog @ 6 months difference of 2.75/70 between treated and placebo group (significant @ 6 but not 12 months) • Standardized MMSE score 2.2/30 higher @12 (but not 3 or 6) months • Intriguing results! • Larger study in planning stages Loeb M, Molloy DW et al JAGS 2004;52:381
    63. 63. Lipid lowering and AD • Previous observations suggested lower risk of AD in those taking “statins” • Recently presented at 8th International Symposium on Advances in AD therapy • Atorvostatin treatment associated with less decline in memory, function, mood & behaviour in people with AD • Premature to decide until full details available in peer reviewed publication
    64. 64. SUMMARY • Dementia relatively uncommon in India at present, but prevalence will rise sharply with aging of population • Best strategies for prevention is control of vascular risk factors, especially hypertension • Social supports more valuable than medications • No cure yet!

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