Effects of Smoking in Forms of Dementia

dementia฀of฀vascular฀origin฀ [123] .฀The฀cholinergic฀effects฀of฀nicotine฀would฀lead฀one฀to฀ expect฀an฀effect฀in฀Alzheimer’s฀disease.฀The฀assumption฀that฀smoking฀has฀an฀Alzheimer- protective฀effect฀received฀due฀attention฀from฀the฀tobacco฀industry.฀These฀results฀were฀not฀ conirmed฀by฀other฀groups฀ [17,฀124] .฀A฀study฀published฀several฀years฀ago฀revealed฀only฀ negative฀effects,฀so฀that฀the฀question฀of฀whether฀nicotine฀has฀an฀effect฀on฀Alzheimer’s฀ disease฀ remains฀ unanswered฀ [125–127] .฀ Also,฀ in฀ a฀ study฀ in฀ 238฀ Alzheimer’s฀ disease฀ patients,฀no฀signiicant฀association฀was฀found฀between฀smoker฀status฀and฀cognitive฀status฀ [128] .฀ A฀ small฀ number฀ of฀ retrospective฀ studies฀ have฀ reported฀ an฀ inverse฀ relationship฀ between฀Alzheimer’s฀disease฀and฀smoking,฀although฀artefacts฀may฀have฀inluenced฀these฀ evaluations฀ [129] .฀The฀neuroprotective฀effects฀of฀smoking฀recorded฀in฀animal฀experiments฀ are฀thus฀not฀transferable฀to฀humans฀ [130] . Smoking฀nicotine฀is฀also฀claimed฀to฀have฀an฀anti-dementia฀effect,฀although฀no฀evi- dence฀has฀been฀found฀to฀support฀this฀claim฀ [28,฀131] .฀Conversely,฀smoking฀increases฀the฀ risk฀of฀stroke฀based฀on฀microcirculatory฀and฀vasoactive฀reactions฀ [132] ,฀so฀that฀dementia฀ from฀vascular฀aetiologies฀may฀also฀result฀from฀long-term฀smoking฀ [129,฀133] .฀The฀pro- spective฀EURODEM฀study฀involving฀male฀British฀doctors฀over฀the฀age฀of฀65฀is฀based฀on฀ this฀thesis฀and฀early฀results฀are฀available฀ [53,฀129] .฀It฀can฀be฀assumed฀that฀smoking฀tends฀ to฀lead฀to฀premature฀rather฀than฀late-onset฀dementia,฀thus฀exacerbating฀and฀complicating฀a฀ primary฀psychotic฀illness.฀According฀to฀the฀Doll฀study฀ [129] ,฀there฀is฀no฀signiicant฀rela- tionship฀between฀smoking฀and฀any฀form฀of฀dementia฀RR฀0.86;฀95฀CI:฀0.55–1.34.฀The฀ prospective฀ studies฀ summarised฀ in฀ Table฀ 7.3 ฀ clearly฀ show฀ that฀ no฀ protective฀ effects฀ of฀ smoking฀against฀developing฀dementia฀have฀been฀demonstrated,฀to฀date,฀in฀humans.฀Instead,฀ it฀must฀be฀assumed฀that฀smoking฀leads฀to฀the฀accelerated฀outbreak฀of฀dementia.

7.1.8 Smoking and Parkinson’s Disease

Various฀epidemiological฀studies฀have฀suggested฀a฀negative฀association฀between฀cigarette฀ smoking฀and฀the฀risk฀of฀Parkinson’s฀disease฀ [134-137] .฀In฀one฀study฀conducted฀over฀a฀total฀ 30-year฀period,฀the฀rate฀ratios฀95฀conidence฀intervals฀for฀Parkinson’s฀disease฀relative฀ Smoking฀ habits Years฀of฀ observation฀ [n] Alzheimer’s฀disease฀ Different฀forms฀of฀dementia References Cases฀ n฀ OR฀95,฀CI Cases฀ n฀ OR฀95,฀CI S a ฀vs.฀NS 3 34 1.1฀0.5–2.4 46 1.4฀0.8–2.7 [26] S฀vs.฀NS 3 76 0.7฀0.3–1.4 – – [138] S฀vs.฀NS 2 277 1.74฀ 1.21–2.50 400 1.39฀1.03–1.89 [51] Curr฀S฀vs.฀ NS 47 370 0.99฀ 0.78–1.25 473 0.96฀0.78–1.18 [125] b Table 7.3 ฀฀฀Smoking฀and฀inluences฀on฀dementia:฀results฀of฀four฀studies a Not฀including฀smokers฀who฀smoked฀5฀cigarettes฀a฀day฀and฀who฀quit฀1–2฀decades฀ago b Study฀involving฀British฀physicians฀and฀based฀on฀smoker฀status฀during฀the฀last฀10–15฀years฀of฀life฀ Curr฀current to฀never-smokers฀was฀0.4฀0.2–0.7฀for฀current฀female฀smokers฀and฀0.3฀0.1–0.8฀for฀cur- rent฀male฀smokers.฀For฀both฀sexes,฀the฀strength฀of฀the฀association฀decreased฀with฀time฀ since฀quitting,฀but฀increased฀with฀the฀number฀of฀cigarettes฀per฀day฀and฀pack-years฀of฀smok- ing฀ [131] .฀An฀inverse฀association฀between฀smoking฀and฀the฀incidence฀of฀Parkinson’s฀dis- ease฀ therefore฀ exists฀ in฀ both฀ men฀ and฀ women฀ [137] .฀ These฀ data฀ were฀ conirmed฀ in฀ a฀ meta-analysis฀ [136] .฀According฀to฀the฀EUROPARKINSON฀Study฀Group,฀a฀family฀history฀ and฀smoking,฀especially฀in฀the฀elderly฀75฀years฀old,฀interact฀synergistically฀to฀increase฀ the฀risk฀for฀the฀development฀of฀Parkinson’s฀disease฀OR฀=฀17.6;฀CI:฀1.9–160.5฀ [137] .฀At฀ the฀same฀time,฀on฀the฀basis฀of฀the฀dopaminergic฀action฀of฀nicotine,฀experimental฀animal฀ work฀tends฀to฀support฀the฀theory฀that฀cigarette฀smoking฀confers฀a฀protective฀effect฀in฀terms฀ of฀Parkinson’s฀disease.฀Recent฀experiments฀in฀mice฀and฀rats฀indicate฀that฀the฀ l -form฀of฀ nicotine฀exerts฀a฀neuroprotective฀effect฀in฀animal฀models฀of฀parkinsonism฀induced฀by฀ diethyldithiocarbamate฀or฀methamphetamine฀ [138] .฀Initial฀studies฀in฀humans฀also฀conirm฀ that฀nicotine฀administration฀slow฀intravenous฀infusion฀followed฀by฀transdermal฀nicotine฀ patch฀application฀leads฀to฀improvements฀in฀extrapyramidal฀functioning฀and฀reaction฀time,฀ and฀to฀decreased฀tracking฀errors฀ [139] . Neuroleptic-induced฀ parkinsonism฀ in฀ smokers฀ is฀ associated฀ with฀ higher฀ neuroleptic฀ doses฀ [140] .฀Evidently,฀by฀increasing฀the฀induction฀of฀drug-metabolising฀enzymes฀in฀the฀ liver,฀the฀smoker฀attempts฀to฀reduce฀the฀unwanted฀effects฀of฀neuroleptics.

7.2 Ocular Diseases

Unlike฀the฀ears,฀eyes฀are฀very฀much฀more฀at฀risk฀from฀the฀effects฀smoking฀than฀was฀previ- ously฀assumed.฀When฀the฀increased฀level฀of฀risk฀associated฀with฀smoking฀is฀present฀in฀con- junction฀with฀other฀risk฀factors,฀numerous฀ocular฀diseases฀may฀occur฀in฀intensiied฀form.฀ Pupil฀ diameter฀ in฀ smokers,฀ immediately฀ after฀ smoking฀ one฀ tobacco฀ cigarette,฀ is฀ slightly฀ smaller฀than฀that฀of฀non-smokers฀after฀sham-smoking฀ [141] . This฀is฀another฀ield฀in฀which฀hardly฀any฀publication฀differentiates฀the฀effects฀of฀nico- tine฀from฀those฀of฀inhaled฀smoke.฀Chronic฀hypoxaemia฀over฀a฀period฀of฀decades฀clearly฀ also฀plays฀a฀pivotal฀role฀in฀the฀context฀of฀eye฀disease.฀It฀is฀therefore฀unsurprising฀that฀the฀ number฀ of฀ ocular฀ diseases฀ in฀ cigarette฀ smokers฀ has฀ not฀ only฀ undergone฀ a฀ quantitative฀ increase,฀but฀also฀that฀more฀ocular฀diseases฀are฀thought฀to฀be฀associated฀with฀smoking฀ [142] .฀Aside฀from฀diabetic฀retinopathy฀and฀open-angle฀glaucoma,฀macular฀degeneration฀ often฀leading฀to฀blindness,฀Graves’฀ophthalmopathy,฀and฀lens฀opacity฀cataract฀develop- ment฀have฀recently฀been฀linked฀with฀smoking.

7.2.1 Diabetic Retinopathy

As฀with฀other฀complications฀of฀type฀I฀or฀II฀diabetes฀mellitus,฀a฀special฀role฀in฀the฀pathogen- esis฀is฀played฀by฀glycated฀proteins,฀including฀haemoglobin,฀which฀are฀deposited฀in฀various฀